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1. HSA Adductomics Reveals Sex Differences in NHL Incidence and Possible Involvement of Microbial Translocation.

Author: Grigoryan, Hasmik, Imani, Partow, Sacerdote, Carlotta, Masala, Giovanna, Grioni, Sara, Tumino, Rosario, Chiodini, Paolo, Dudoit, Sandrine, Vineis, Paolo, and Rappaport, Stephen M
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Lymphoma, Hematology, Cancer, Aetiology, 2.2 Factors relating to the physical environment, Humans, Male, Female, Serum Albumin, Human, Reactive Oxygen Species, Sex Characteristics, Incidence, Prospective Studies, Cysteine, Lymphoma, Non-Hodgkin, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract: BackgroundThe higher incidence of non-Hodgkin lymphoma (NHL) in males is not well understood. Although reactive oxygen species (ROS) have been implicated as causes of NHL, they cannot be measured directly in archived blood.MethodsWe performed untargeted adductomics of stable ROS adducts in human serum albumin (HSA) from 67 incident NHL cases and 82 matched controls from the European Prospective Investigation into Cancer and Nutrition-Italy cohort. Regression and classification methods were employed to select features associated with NHL in all subjects and in males and females separately.ResultsSixty seven HSA-adduct features were quantified by liquid chromatography-high-resolution mass spectrometry at Cys34 (n = 55) and Lys525 (n = 12). Three features were selected for association with NHL in all subjects, while seven were selected for males and five for females with minimal overlap. Two selected features were more abundant in cases and seven in controls, suggesting that altered homeostasis of ROS may affect NHL incidence. Heat maps revealed differential clustering of features between sexes, suggesting differences in operative pathways.ConclusionsAdduct clusters dominated by Cys34 oxidation products and disulfides further implicate ROS and redox biology in the etiology of NHL. Sex differences in dietary and alcohol consumption also help to explain the limited overlap of feature selection between sexes. Intriguingly, a disulfide of methanethiol from enteric microbial metabolism was more abundant in male cases, thereby implicating microbial translocation as a potential contributor to NHL in males.ImpactOnly two of the ROS adducts associated with NHL overlapped between sexes and one adduct implicates microbial translocation as a risk factor.
Published: 2023

2. Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease

Author: Agha, Golareh, Mendelson, Michael M, Ward-Caviness, Cavin K, Joehanes, Roby, Huan, TianXiao, Gondalia, Rahul, Salfati, Elias, Brody, Jennifer A, Fiorito, Giovanni, Bressler, Jan, Chen, Brian H, Ligthart, Symen, Guarrera, Simonetta, Colicino, Elena, Just, Allan C, Wahl, Simone, Gieger, Christian, Vandiver, Amy R, Tanaka, Toshiko, Hernandez, Dena G, Pilling, Luke C, Singleton, Andrew B, Sacerdote, Carlotta, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Li, Yun, Zhang, Guosheng, Stewart, James D, Floyd, James S, Wiggins, Kerri L, Rotter, Jerome I, Multhaup, Michael, Bakulski, Kelly, Horvath, Steven, Tsao, Philip S, Absher, Devin M, Vokonas, Pantel, Hirschhorn, Joel, Fallin, M Daniele, Liu, Chunyu, Bandinelli, Stefania, Boerwinkle, Eric, Dehghan, Abbas, Schwartz, Joel D, Psaty, Bruce M, Feinberg, Andrew P, Hou, Lifang, Ferrucci, Luigi, Sotoodehnia, Nona, Matullo, Giuseppe, Peters, Annette, Fornage, Myriam, Assimes, Themistocles L, Whitsel, Eric A, Levy, Daniel, and Baccarelli, Andrea A
Subjects: Human Genome, Heart Disease, Clinical Research, Prevention, Heart Disease - Coronary Heart Disease, Atherosclerosis, Cardiovascular, Genetics, Adult, Aged, Cohort Studies, Coronary Disease, CpG Islands, DNA Methylation, Europe, Female, Genome-Wide Association Study, Humans, Incidence, Leukocytes, Male, Middle Aged, Myocardial Infarction, Population Groups, Prognosis, Prospective Studies, Risk, United States, coronary artery disease, coronary heart disease, epigenetics, genomics, gene expression regulation, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract: BackgroundDNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.MethodsNine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts.ResultsAmong 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate
Published: 2019

3. MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort

Author: Pellegrini, Cristina, Botta, Francesca, Massi, Daniela, Martorelli, Claudia, Facchetti, Fabio, Gandini, Sara, Maisonneuve, Patrick, Avril, Marie-Françoise, Demenais, Florence, Paillerets, Brigitte Bressac-de, Hoiom, Veronica, Cust, Anne E, Anton-Culver, Hoda, Gruber, Stephen B, Gallagher, Richard P, Marrett, Loraine, Zanetti, Roberto, Dwyer, Terence, Thomas, Nancy E, Begg, Colin B, Berwick, Marianne, Puig, Susana, Potrony, Miriam, Nagore, Eduardo, Ghiorzo, Paola, Menin, Chiara, Manganoni, Ausilia Maria, Rodolfo, Monica, Brugnara, Sonia, Passoni, Emanuela, Sekulovic, Lidija Kandolf, Baldini, Federica, Guida, Gabriella, Stratigos, Alexandros, Ozdemir, Fezal, Ayala, Fabrizio, Fernandez-de-Misa, Ricardo, Quaglino, Pietro, Ribas, Gloria, Romanini, Antonella, Migliano, Emilia, Stanganelli, Ignazio, Kanetsky, Peter A, Pizzichetta, Maria Antonietta, García-Borrón, Jose Carlos, Nan, Hongmei, Landi, Maria Teresa, Little, Julian, Newton-Bishop, Julia, Sera, Francesco, Fargnoli, Maria Concetta, Raimondi, Sara, Group, IMI Study, Alaibac, Mauro, Ferrari, Andrea, Valeri, Barbara, Sicher, Mariacristina, Mangiola, Daniela, Nazzaro, Gianluca, Tosti, Giulio, Mazzarol, Giovanni, Giudice, Giuseppe, Ribero, Simone, Astrua, Chiara, Mazzoni, Laura, Group, GEM Study, Orlow, Irene, Mujumdar, Urvi, Hummer, Amanda, Busam, Klaus, Roy, Pampa, Canchola, Rebecca, Clas, Brian, Cotignola, Javiar, Monroe, Yvette, Armstrong, Bruce, Kricker, Anne, Litchfield, Melisa, Tucker, Paul, Stephens, Nicola, Switzer, Teresa, Theis, Beth, From, Lynn, Chowdhury, Noori, Vanasse, Louise, Purdue, Mark, Northrup, David, Rosso, Stefano, Sacerdote, Carlotta, Leighton, Nancy, Gildea, Maureen, Bonner, Joe, Jeter, Joanne, Klotz, Judith, Wilcox, Homer, Weiss, Helen, Millikan, Robert, Mattingly, Dianne, and Player, Jon
Subjects: Clinical Research, Pediatric, Genetics, Prevention, Cancer, Adolescent, Adult, Aged, Biomarkers, Tumor, Case-Control Studies, Child, Female, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Logistic Models, Male, Melanoma, Middle Aged, Odds Ratio, Polymorphism, Genetic, Receptor, Melanocortin, Type 1, Retrospective Studies, Skin Neoplasms, IMI Study Group, GEM Study Group, M-SKIP Study Group
Abstract: BackgroundGermline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls.MethodsIn this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger.FindingsWe analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants.InterpretationOur pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies.FundingSPD-Pilot/Project-Award-2015; AIRC-MFAG-11831.
Published: 2019

4. Alcohol and lung cancer risk among never smokers: A pooled analysis from the international lung cancer consortium and the SYNERGY study

Author: Fehringer, Gordon, Brenner, Darren R, Zhang, Zuo‐Feng, Lee, Yuan‐Chin Amy, Matsuo, Keitaro, Ito, Hidemi, Lan, Qing, Vineis, Paolo, Johansson, Mattias, Overvad, Kim, Riboli, Elio, Trichopoulou, Antonia, Sacerdote, Carlotta, Stucker, Isabelle, Boffetta, Paolo, Brennan, Paul, Christiani, David C, Hong, Yun‐Chul, Landi, Maria Teresa, Morgenstern, Hal, Schwartz, Ann G, Wenzlaff, Angela S, Rennert, Gad, McLaughlin, John R, Harris, Curtis C, Olivo‐Marston, Susan, Orlow, Irene, Park, Bernard J, Zauderer, Marjorie, Dios, Juan M Barros, Raviña, Alberto Ruano, Siemiatycki, Jack, Koushik, Anita, Lazarus, Philip, Fernández‐Somoano, Ana, Tardon, Adonina, Le Marchand, Loic, Brenner, Hermann, Saum, Kai‐Uwe, Duell, Eric J, Andrew, Angeline S, Szeszenia‐Dabrowska, Neonila, Lissowska, Jolanta, Zaridze, David, Rudnai, Peter, Fabianova, Eleonora, Mates, Dana, Foretova, Lenka, Janout, Vladimir, Bencko, Vladimir, Holcatova, Ivana, Pesatori, Angela Cecilia, Consonni, Dario, Olsson, Ann, Straif, Kurt, and Hung, Rayjean J
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Lung, Cancer, Substance Misuse, Tobacco, Alcoholism, Alcohol Use and Health, Tobacco Smoke and Health, Prevention, Lung Cancer, Cardiovascular, Stroke, Respiratory, Good Health and Well Being, Aged, Alcohol Drinking, Alcoholic Beverages, Asia, Case-Control Studies, Cohort Studies, Europe, Female, Humans, Lung Neoplasms, Male, Middle Aged, North America, Risk Factors, Smoking, alcohol, lung cancer, wine, beer, liquor, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.
Published: 2017

5. Variants in autophagy‐related genes and clinical characteristics in melanoma: a population‐based study

Author: White, Kirsten AM, Luo, Li, Thompson, Todd A, Torres, Salina, Hu, Chien‐An Andy, Thomas, Nancy E, Lilyquist, Jenna, Anton‐Culver, Hoda, Gruber, Stephen B, From, Lynn, Busam, Klaus J, Orlow, Irene, Kanetsky, Peter A, Marrett, Loraine D, Gallagher, Richard P, Sacchetto, Lidia, Rosso, Stefano, Dwyer, Terence, Cust, Anne E, Begg, Colin B, Berwick, Marianne, Mujumdar, Urvi, Roy, Pampa, Armstrong, Bruce, Kricker, Anne, Litchfield, Melisa, Tucker, Paul, Venn, Alison, Stephens, Nicola, Switzer, Teresa, Marrett, Loraine, Theis, Elizabeth, Chowdhury, Noori, Vanasse, Louise, Zanetti, Roberto, Sacerdote, Carlotta, Leighton, Nancy, Jeter, Joanne, Klotz, Judith, Wilcox, Homer, Weiss, Helen, Mattingly, Dianne, Player, Jon, Rebbeck, Timothy, Walker, Amy, Panossian, Saarene, Taylor, Julia Lee, and Madronich, Sasha
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetics, Clinical Research, Aetiology, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, 2.1 Biological and endogenous factors, Adult, Aged, Alleles, Autophagy, Autophagy-Related Proteins, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Male, Melanoma, Middle Aged, Models, Biological, Neoplasm Staging, Odds Ratio, Polymorphism, Single Nucleotide, Population Surveillance, ATG16L1, autophagy, melanoma, polymorphism, SNP, GEM Study Group, ATG16L1, SNP, Biochemistry and Cell Biology, Oncology and carcinogenesis
Abstract: Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27-0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11-1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12-3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05-0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21-0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34-0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression.
Published: 2016

6. Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry

Author: Figueroa, Jonine D, Middlebrooks, Candace D, Banday, A Rouf, Ye, Yuanqing, Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Koutros, Stella, Kiemeney, Lambertus A, Rafnar, Thorunn, Bishop, Timothy, Furberg, Helena, Matullo, Giuseppe, Golka, Klaus, Gago-Dominguez, Manuela, Taylor, Jack A, Fletcher, Tony, Siddiq, Afshan, Cortessis, Victoria K, Kooperberg, Charles, Cussenot, Olivier, Benhamou, Simone, Prescott, Jennifer, Porru, Stefano, Dinney, Colin P, Malats, Núria, Baris, Dalsu, Purdue, Mark P, Jacobs, Eric J, Albanes, Demetrius, Wang, Zhaoming, Chung, Charles C, Vermeulen, Sita H, Aben, Katja K, Galesloot, Tessel E, Thorleifsson, Gudmar, Sulem, Patrick, Stefansson, Kari, Kiltie, Anne E, Harland, Mark, Teo, Mark, Offit, Kenneth, Vijai, Joseph, Bajorin, Dean, Kopp, Ryan, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Selinski, Silvia, Hengstler, Jan G, Gerullis, Holger, Ovsiannikov, Daniel, Blaszkewicz, Meinolf, Castelao, Jose Esteban, Calaza, Manuel, Martinez, Maria Elena, Cordeiro, Patricia, Xu, Zongli, Panduri, Vijayalakshmi, Kumar, Rajiv, Gurzau, Eugene, Koppova, Kvetoslava, Bueno-De-Mesquita, H Bas, Ljungberg, Börje, Clavel-Chapelon, Françoise, Weiderpass, Elisabete, Krogh, Vittorio, Dorronsoro, Miren, Travis, Ruth C, Tjønneland, Anne, Brennan, Paul, Chang-Claude, Jenny, Riboli, Elio, Conti, David, Stern, Marianna C, Pike, Malcolm C, Van Den Berg, David, Yuan, Jian-Min, Hohensee, Chancellor, Jeppson, Rebecca P, Cancel-Tassin, Geraldine, Roupret, Morgan, Comperat, Eva, Turman, Constance, De Vivo, Immaculata, Giovannucci, Edward, Hunter, David J, Kraft, Peter, Lindstrom, Sara, Carta, Angela, Pavanello, Sofia, Arici, Cecilia, Mastrangelo, Giuseppe, Kamat, Ashish M, Zhang, Liren, Gong, Yilei, Pu, Xia, Hutchinson, Amy, Burdett, Laurie, Wheeler, William A, and Karagas, Margaret R
Subjects: Cancer, Prevention, Human Genome, Genetics, Biotechnology, Urologic Diseases, Aetiology, 2.1 Biological and endogenous factors, Biomarkers, Tumor, Case-Control Studies, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 20, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Polymorphism, Single Nucleotide, Risk Factors, Urinary Bladder Neoplasms, White People, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract: Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.
Published: 2016

7. Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Author: Obón-Santacana, M, Kaaks, R, Slimani, N, Lujan-Barroso, L, Freisling, H, Ferrari, P, Dossus, L, Chabbert-Buffet, N, Baglietto, L, Fortner, RT, Boeing, H, Tjønneland, A, Olsen, A, Overvad, K, Menéndez, V, Molina-Montes, E, Larrañaga, N, Chirlaque, M-D, Ardanaz, E, Khaw, K-T, Wareham, N, Travis, RC, Lu, Y, Merritt, MA, Trichopoulou, A, Benetou, V, Trichopoulos, D, Saieva, C, Sieri, S, Tumino, R, Sacerdote, C, Galasso, R, Bueno-de-Mesquita, HB, Wirfält, E, Ericson, U, Idahl, A, Ohlson, N, Skeie, G, Gram, IT, Weiderpass, E, Onland-Moret, NC, Riboli, E, and Duell, EJ
Subjects: Biomedical and Clinical Sciences, Nutrition and Dietetics, Nutrition, Clinical Research, Prevention, Cancer, Aetiology, 2.2 Factors relating to the physical environment, Cardiovascular, Acrylamide, Cohort Studies, Diet, Eating, Endometrial Neoplasms, Female, Humans, Middle Aged, Nutritional Status, Prospective Studies, Risk, Risk Factors, Smoking, acrylamide, endometrial cancer, type-I endometrial cancer, cohort, nutrition, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: BackgroundThree prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk.MethodsCox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method.ResultsNo associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood ratio test (LRT) P-value: 0.01, n=203).ConclusionsDietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.
Published: 2014

8. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.

Author: Holmes, Michael V, Dale, Caroline E, Zuccolo, Luisa, Silverwood, Richard J, Guo, Yiran, Ye, Zheng, Prieto-Merino, David, Dehghan, Abbas, Trompet, Stella, Wong, Andrew, Cavadino, Alana, Drogan, Dagmar, Padmanabhan, Sandosh, Li, Shanshan, Yesupriya, Ajay, Leusink, Maarten, Sundstrom, Johan, Hubacek, Jaroslav A, Pikhart, Hynek, Swerdlow, Daniel I, Panayiotou, Andrie G, Borinskaya, Svetlana A, Finan, Chris, Shah, Sonia, Kuchenbaecker, Karoline B, Shah, Tina, Engmann, Jorgen, Folkersen, Lasse, Eriksson, Per, Ricceri, Fulvio, Melander, Olle, Sacerdote, Carlotta, Gamble, Dale M, Rayaprolu, Sruti, Ross, Owen A, McLachlan, Stela, Vikhireva, Olga, Sluijs, Ivonne, Scott, Robert A, Adamkova, Vera, Flicker, Leon, Bockxmeer, Frank M van, Power, Christine, Marques-Vidal, Pedro, Meade, Tom, Marmot, Michael G, Ferro, Jose M, Paulos-Pinheiro, Sofia, Humphries, Steve E, Talmud, Philippa J, Mateo Leach, Irene, Verweij, Niek, Linneberg, Allan, Skaaby, Tea, Doevendans, Pieter A, Cramer, Maarten J, van der Harst, Pim, Klungel, Olaf H, Dowling, Nicole F, Dominiczak, Anna F, Kumari, Meena, Nicolaides, Andrew N, Weikert, Cornelia, Boeing, Heiner, Ebrahim, Shah, Gaunt, Tom R, Price, Jackie F, Lannfelt, Lars, Peasey, Anne, Kubinova, Ruzena, Pajak, Andrzej, Malyutina, Sofia, Voevoda, Mikhail I, Tamosiunas, Abdonas, Maitland-van der Zee, Anke H, Norman, Paul E, Hankey, Graeme J, Bergmann, Manuela M, Hofman, Albert, Franco, Oscar H, Cooper, Jackie, Palmen, Jutta, Spiering, Wilko, de Jong, Pim A, Kuh, Diana, Hardy, Rebecca, Uitterlinden, Andre G, Ikram, M Arfan, Ford, Ian, Hyppönen, Elina, Almeida, Osvaldo P, Wareham, Nicholas J, Khaw, Kay-Tee, Hamsten, Anders, Husemoen, Lise Lotte N, Tjønneland, Anne, Tolstrup, Janne S, Rimm, Eric, Beulens, Joline WJ, and Verschuren, WM Monique
Subjects: InterAct Consortium, Humans, Coronary Disease, Alcohol Dehydrogenase, Genetic Markers, Models, Statistical, Alcohol Drinking, Genotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Female, Male, Stroke, Mendelian Randomization Analysis, Biomarkers, General & Internal Medicine, Clinical Sciences, Public Health and Health Services
Abstract: ObjectiveTo use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.DesignMendelian randomisation meta-analysis of 56 epidemiological studies.Participants261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers.Main outcome measuresOdds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.ResultsCarriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)).ConclusionsIndividuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.
Published: 2014

9. Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis

Author: Chadeau-Hyam, M, Vermeulen, RCH, Hebels, DGAJ, Castagné, R, Campanella, G, Portengen, L, Kelly, RS, Bergdahl, IA, Melin, B, Hallmans, G, Palli, D, Krogh, V, Tumino, R, Sacerdote, C, Panico, S, de Kok, TMCM, Smith, MT, Kleinjans, JCS, Vineis, P, Kyrtopoulos, SA, consortium, on behalf of the EnviroGenoMarkers project, Georgiadis, P, Botsivali, M, Papadopoulou, C, Chatziioannou, A, Valavanis, I, Gottschalk, R, van Leeuwen, D, Timmermans, L, Keun, HC, Athersuch, TJ, Lenner, P, Bendinelli, B, Stephanou, EG, Myridakis, A, Kogevinas, M, Saberi-Hosnijeh, F, Fazzo, L, de Santis, M, Comba, P, Kiviranta, H, Rantakokko, P, Airaksinen, R, Ruokojarvi, P, Gilthorpe, MS, Fleming, S, Fleming, T, Tu, Y-K, Jonsson, B, Lundh, T, Chien, K-L, Chen, WJ, Lee, W-C, Hsiao, CK, Kuo, P-H, Hung, H, and Liao, S-F
Subjects: Genetic Testing, Lymphoma, Orphan Drug, Genetics, Hematology, Cancer, Rare Diseases, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Biomarkers, Tumor, Case-Control Studies, Female, Genome, Human, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Models, Genetic, Principal Component Analysis, Prospective Studies, Transcriptome, epidemiology, lymphoma, chronic lymphocytic leukemia, mRNA analyses, prospective cohort, EnviroGenoMarkers project consortium, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract: BackgroundB-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms.MethodsWe investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts.ResultsOur analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection.ConclusionsThis is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.
Published: 2014

10. Baseline and lifetime alcohol consumption and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort ( <scp>EPIC</scp> )

Author: Yahya Mahamat‐Saleh, Marie Al‐Rahmoun, Gianluca Severi, Reza Ghiasvand, Marit B. Veierod, Saverio Caini, Domenico Palli, Edoardo Botteri, Carlotta Sacerdote, Fulvio Ricceri, Marko Lukic, Maria J. Sánchez, Valeria Pala, Rosario Tumino, Paolo Chiodini, Pilar Amiano, Sandra Colorado‐Yohar, María‐Dolores Chirlaque, Eva Ardanaz, Catalina Bonet, Verena Katzke, Rudolf Kaaks, Matthias B. Schulze, Kim Overvad, Christina C. Dahm, Christian S. Antoniussen, Anne Tjønneland, Cecilie Kyrø, Bas Bueno‐de‐Mesquita, Jonas Manjer, Malin Jansson, Anders Esberg, Nagisa Mori, Pietro Ferrari, Elisabete Weiderpass, Marie‐Christine Boutron‐Ruault, Marina Kvaskoff, Mahamat-Saleh, Yahya, Al-Rahmoun, Marie, Severi, Gianluca, Ghiasvand, Reza, Veierod, Marit B, Caini, Saverio, Palli, Domenico, Botteri, Edoardo, Sacerdote, Carlotta, Ricceri, Fulvio, Lukic, Marko, Sánchez, Maria J, Pala, Valeria, Tumino, Rosario, Chiodini, Paolo, Amiano, Pilar, Colorado-Yohar, Sandra, Chirlaque, María-Dolore, Ardanaz, Eva, Bonet, Catalina, Katzke, Verena, Kaaks, Rudolf, Schulze, Matthias B, Overvad, Kim, Dahm, Christina C, Antoniussen, Christian S, Tjønneland, Anne, Kyrø, Cecilie, Bueno-de-Mesquita, Ba, Manjer, Jona, Jansson, Malin, Esberg, Ander, Mori, Nagisa, Ferrari, Pietro, Weiderpass, Elisabete, Boutron-Ruault, Marie-Christine, and Kvaskoff, Marina
Subjects: Male, Cancer och onkologi, Cancer Research, Skin Neoplasms, Alcohol Drinking, alcohol, keratinocyte cancers, Public Health, Global Health, Social Medicine and Epidemiology, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, cutaneous melanoma, cohort studies, Oncology, Carcinoma, Basal Cell, Risk Factors, Cancer and Oncology, Carcinoma, Squamous Cell, epidemiology, Humans, Female, Prospective Studies, Melanoma, cohort studie
Abstract: Experimental evidence suggests that alcohol induces cutaneous carcinogenesis, yet epidemiological studies on the link between alcohol intake and skin cancer have been inconsistent. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort initiated in 1992 in 10 European countries. Alcohol intake at baseline and average lifetime alcohol intake were assessed using validated country-specific dietary and lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in Cox models. A total of 14 037 skin cancer cases (melanoma: n = 2457; basal-cell carcinoma (BCC): n = 8711; squamous-cell carcinoma (SCC): n = 1928; unknown: n = 941) were identified among 450 112 participants (average follow-up: 15 years). Baseline alcohol intake was positively associated with SCC (>15 vs 0.1-4.9 g/day: HR = 1.44, 95% CI = 1.17-1.77; Ptrend = .001), BCC (HR = 1.12, 95% CI = 1.01-1.23; Ptrend = .04), and melanoma risks in men (HR = 1.17, 95% CI = 0.95-1.44; Ptrend = .17), while associations were more modest in women (SCC: HR = 1.09, 95% CI = 0.90-1.30; Ptrend = .13; BCC: HR = 1.08, 95% CI = 1.00-1.17,Ptrend = .03; melanoma: HR = 0.93, 95% CI = 0.80-1.08, Ptrend = .13). Associations were similar for lifetime alcohol intake, with an attenuated linear trend. Lifetime liquor/spirit intake was positively associated with melanoma (fourth vs first quartile: HR = 1.47, 95% CI = 1.08-1.99; Ptrend = .0009) and BCC risks in men (HR = 1.17, 95% CI = 1.04-1.31;Ptrend = .14). Baseline and lifetime intakes of wine were associated with BCC risk (HR = 1.25 in men; HR = 1.11-1.12; in women). No statistically significant associations were found between beverage types and SCC risk. Intake of beer was not associated with skin cancer risk. Our study suggests positive relationships between alcohol intake and skin cancer risk, which may have important implications for the primary prevention of skin cancer. What's new? Drinking alcohol can make the skin more sensitive to sunlight and vulnerable to skin cancer. Here, the authors conducted a large prospective cohort study to evaluate whether alcohol consumption correlates with skin cancer risk. Among the 450 112 participants, there were 2457 cases of melanoma, 8711 of basal cell carcinoma, and 1928 of squamous cell carcinoma. There was a positive association between alcohol and all three cancer types, stronger in men than in women. The association varied somewhat by beverage type.
Published: 2022
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11. A body shape index (ABSI) is associated inversely with post-menopausal progesterone-receptor-negative breast cancer risk in a large European cohort

Author: Christakoudi, S, Tsilidis, KK, Dossus, L, Rinaldi, S, Weiderpass, E, Antoniussen, CS, Dahm, CC, Tjønneland, A, Mellemkjær, L, Katzke, V, Kaaks, R, Schulze, MB, Masala, G, Grioni, S, Panico, S, Tumino, R, Sacerdote, C, May, AM, Monninkhof, EM, Quirós, JR, Bonet, C, Sánchez, M-J, Amiano, P, Chirlaque, M-D, Guevara, M, Rosendahl, AH, Stocks, T, Perez-Cornago, A, Tin Tin, S, Heath, AK, Aglago, EK, Peruchet-Noray, L, Freisling, H, and Riboli, E
Subjects: Breast Neoplasms/complications, Somatotypes, Hip Size, Triple Negative Breast Neoplasms/complications, Waist Size, Middle Aged, Body Mass Index, Postmenopause, ABSI, Body shape, Breast cancer, Risk Factors, Humans, Female, Prospective Studies, Obesity, Progesterone
Abstract: BACKGROUND: Associations of body shape with breast cancer risk, independent of body size, are unclear because waist and hip circumferences are correlated strongly positively with body mass index (BMI).METHODS: We evaluated body shape with the allometric "a body shape index" (ABSI) and hip index (HI), which compare waist and hip circumferences, correspondingly, among individuals with the same weight and height. We examined associations of ABSI, HI, and BMI (per one standard deviation increment) with breast cancer overall, and according to menopausal status at baseline, age at diagnosis, and oestrogen and progesterone receptor status (ER+/-PR+/-) in multivariable Cox proportional hazards models using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.RESULTS: During a mean follow-up of 14.0 years, 9011 incident breast cancers were diagnosed among 218,276 women. Although there was little evidence for association of ABSI with breast cancer overall (hazard ratio HR = 0.984; 95% confidence interval: 0.961-1.007), we found borderline inverse associations for post-menopausal women (HR = 0.971; 0.942-1.000; n = 5268 cases) and breast cancers diagnosed at age ≥ 55 years (HR = 0.976; 0.951-1.002; n = 7043) and clear inverse associations for ER + PR- subtypes (HR = 0.894; 0.822-0.971; n = 726) and ER-PR- subtypes (HR = 0.906; 0.835-0.983 n = 759). There were no material associations with HI. BMI was associated strongly positively with breast cancer overall (HR = 1.074; 1.049-1.098), for post-menopausal women (HR = 1.117; 1.085-1.150), for cancers diagnosed at age ≥ 55 years (HR = 1.104; 1.076-1.132), and for ER + PR + subtypes (HR = 1.122; 1.080-1.165; n = 3101), but not for PR- subtypes.CONCLUSIONS: In the EPIC cohort, abdominal obesity evaluated with ABSI was not associated with breast cancer risk overall but was associated inversely with the risk of post-menopausal PR- breast cancer. Our findings require validation in other cohorts and with a larger number of PR- breast cancer cases.
Published: 2023
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12. Association between classes and subclasses of polyphenol intake and 5‐year body weight changes in the EPIC‐PANACEA study

Author: Jazmin Castañeda, Mercedes Gil‐Lespinard, Enrique Almanza‐Aguilera, Fjorida Llaha, Jesús‐Humberto Gómez, Nicola Bondonno, Anne Tjønneland, Kim Overvad, Verena Katzke, Matthias B. Schulze, Giovanna Masala, Claudia Agnoli, Maria Santucci de Magistris, Rosario Tumino, Carlotta Sacerdote, Guri Skeie, Magritt Brustad, Cristina Lasheras, Esther Molina‐Montes, María‐Dolores Chirlaque, Aurelio Barricarte, Emily Sonestedt, Marisa da Silva, Ingegerd Johansson, Johan Hultdin, Anne M. May, Nita G. Forouhi, Alicia K. Heath, Heinz Freisling, Elisabete Weiderpass, Augustin Scalbert, Raul Zamora‐Ros, Castañeda, Jazmin [0000-0002-8521-9946], Gil-Lespinard, Mercedes [0000-0002-7387-2139], Almanza-Aguilera, Enrique [0000-0002-4805-0774], Llaha, Fjorida [0000-0003-0534-6484], Gómez, Jesús-Humberto [0000-0001-8442-8327], Bondonno, Nicola [0000-0001-5905-444X], Tjønneland, Anne [0000-0003-4385-2097], Overvad, Kim [0000-0001-6429-7921], Katzke, Verena [0000-0002-6509-6555], Schulze, Matthias B [0000-0002-0830-5277], Masala, Giovanna [0000-0002-5758-9069], Agnoli, Claudia [0000-0003-4472-1179], Tumino, Rosario [0000-0003-2666-414X], Sacerdote, Carlotta [0000-0002-8008-5096], Skeie, Guri [0000-0003-2476-4251], Brustad, Magritt [0000-0003-0114-5271], Lasheras, Cristina [0000-0003-0482-4229], Molina-Montes, Esther [0000-0002-0428-2426], Chirlaque, María-Dolores [0000-0001-9242-3040], Barricarte, Aurelio [0000-0001-6750-1270], Sonestedt, Emily [0000-0002-0747-4562], da Silva, Marisa [0000-0003-1215-8625], Johansson, Ingegerd [0000-0002-9227-8434], Hultdin, Johan [0000-0002-9599-0961], Forouhi, Nita G [0000-0002-5041-248X], Heath, Alicia K [0000-0001-6517-1300], Freisling, Heinz [0000-0001-8648-4998], Weiderpass, Elisabete [0000-0003-2237-0128], Scalbert, Augustin [0000-0001-6651-6710], Zamora-Ros, Raul [0000-0002-6236-6804], and Apollo - University of Cambridge Repository
Subjects: Male, Flavonoids, Nutrition and Dietetics, Coumaric Acids, Endocrinology, Diabetes and Metabolism, Body Weight, Medicine (miscellaneous), Polyphenols, Weight Gain, Coffee, Diet, Näringslära, Endocrinology, Neoplasms, Humans, Female, Prospective Studies
Abstract: Objective: The aim of this study was to evaluate the associations among the intake of total polyphenols, polyphenol classes, and polyphenol subclasses and body weight change over 5years. Methods: A total of 349,165 men and women aged 25 to 70years were recruited in the Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (PANACEA) project of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries. Body weight was measured at baseline and at follow-up after a median time of 5years. Polyphenol intake, including four main polyphenol classes and eighteen subclasses, was estimated using validated dietary questionnaires and Phenol-Explorer. Multilevel mixed linear regression models were used to estimate the associations. Results: Participants gained, on average, 2.6 kg (5.0 kg) over 5years. Total flavonoids intake was inversely associated with body weight change (-0.195kg/5 years, 95% CI: -0.262 to -0.128). However, the intake of total polyphenols (0.205kg/5 years, 95% CI: 0.138 to 0.272) and intake of hydroxycinnamic acids (0.324kg/5 years, 95% CI: 0.267 to 0.381) were positively associated with body weight gain. In analyses stratified by coffee consumption, hydroxycinnamic acid intake was positively associated with body weight gain in coffee consumers (0.379kg/5 years, 95% CI: 0.319 to 0.440), but not in coffee nonconsumers (-0.179kg/5 years, 95% CI: -0.490 to 0.133). Conclusions: Higher intakes of flavonoids and their subclasses are inversely associated with a modest body weight change. Results regarding hydroxycinnamic acids in coffee consumers require further investigation., Consejo Nacional de Ciencia y Tecnologia (CONACyT) 693636, Instituto de Salud Carlos III CD20/ 00071 CPII20/00009 FI19/00185 PI18/ 00191
Published: 2022
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13. Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals, a prospective longitudinal cohort study

Author: Shirley Shapiro Ben David, Barak Mizrahi, Daniella Rahamim-Cohen, Lia Supino-Rosin, Arnon Shahar, Sharon Hermoni-Alon, Ariela Fremder Sacerdote, Angela Irony, Rachel Lazar, Nir Kalkstein, Yaniv Lustig, Victoria Indenbaum, Daniel Landsberger, Miri Mizrahi-Reuveni, and Shirley Shapira
Subjects: Male, Vaccines, General Veterinary, General Immunology and Microbiology, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, Middle Aged, Antibodies, Viral, Infectious Diseases, Immunoglobulin G, Antibody Formation, Humans, Molecular Medicine, Female, Longitudinal Studies, Prospective Studies, BNT162 Vaccine
Abstract: As protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.A prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.Among 110 participants,56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25-11.67) folds and 2.40 (95 %CI 1.90-3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5-79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1-34.7) fold in and immunocompetent group, was observed.A third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.
Published: 2022
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14. Male breast cancer after childhood cancer

Author: Yuehan Wang, Raoul C. Reulen, Leontien C.M. Kremer, Florent de Vathaire, Riccardo Haupt, Lorna Zadravec Zaletel, Francesca Bagnasco, Charlotte Demoor-Goldschmidt, Willem J. van Dorp, Nadia Haddy, Lars Hjorth, Zsuzsanna Jakab, Claudia E. Kuehni, Päivi M. Lähteenmäki, Helena J.H. van der Pal, Carlotta Sacerdote, Roderick Skinner, Monica Terenziani, Finn Wesenberg, Jeanette F. Winther, Flora E. van Leeuwen, Mike M. Hawkins, Jop C. Teepen, Elvira C. van Dalen, Cécile M. Ronckers, Paediatric Oncology, CCA - Cancer Treatment and Quality of Life, and ARD - Amsterdam Reproduction and Development
Subjects: Adult, Male, Cancer Research, Data analyses, Incidence, Late effects, Breast Neoplasms, Male, Childhood cancer survivors, Male breast cancer, Cohort Studies, Oncology, Cancer Survivors, Risk Factors, Second cancer, Neoplasms, Systematic review, Humans, Female, Registries, 610 Medicine & health, Child, Cohort study, 360 Social problems & social services
Abstract: BACKGROUND Breast cancer is a well-recognised late adverse effect in female childhood cancer survivors (CCSs), especially after chest radiotherapy; information on subsequent male breast cancer (SMBC) is limited. We summarised the existing evidence on SMBC after childhood cancer in a systematic review��and investigated the risk of SMBC among males in a Pan-European cohort. METHODS We searched Medline/PubMed for cohort studies and case reports/series that assessed SMBC after childhood cancer (��21 years). Furthermore, we analysed data on SMBC in the PanCareSurFup cohort, reporting standardised incidence ratios (SIRs), absolute excess risks (AERs), and 5- and 10-year survival rates. RESULTS The systematic review included 38 of 7080 potentially eligible articles. Cohort-specific SMBC frequencies were 0-0.40% (31 studies). SMBC occurred after a follow-up ranging from 24.0 to 42.0 years. Nine case reports/series described 11 SMBC cases, occurring 11.0-42.5 years after primary childhood cancer. In the PanCareSurFup cohort (16 SMBC/37,738 males; 0.04%), we observed a 22.3-fold increased risk of SMBC relative to the general male population (95% CI 12.7-36.2; absolute excess risk/100,000 person-years: 2.3, 95% CI 1.3-3.7). The five- and ten-year survival rates after SMBC diagnosis were 60.3% (95% CI 35.6%-85.0%) and 43.0% (95% CI 16.1%-69.9%), respectively. Clear evidence of risk factors did not emerge from these comprehensive efforts. CONCLUSIONS Compared to the general population, male CCSs have an elevated risk of developing subsequent breast cancer, although the absolute risk is low. Health care providers should be aware of this rare yet serious late effect; male CCSs with symptoms potentially related to SMBC warrant careful examination.
Published: 2022
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15. Cigarette Smoking and Endometrial Cancer Risk:Observational and Mendelian Randomization Analyses

Author: Dimou, N, Omiyale, W, Biessy, C, Viallon, V, Kaaks, R, O'Mara, TA, Aglago, EK, Ardanaz, E, Bergmann, MM, Bondonno, NP, Braaten, T, Colorado-Yohar, SM, Crous-Bou, M, Dahm, CC, Fortner, RT, Gram, IT, Harlid, S, Heath, AK, Idahl, A, Kvaskoff, M, Nøst, TH, Overvad, K, Palli, D, Perez-Cornago, A, Sacerdote, C, Sánchez, M-J, Schulze, MB, Severi, G, Simeon, V, Tagliabue, G, Tjønneland, A, Truong, T, Tumino, R, Johansson, M, Weiderpass, E, Murphy, N, Gunter, MJ, Lacey, B, Allen, NE, Dossus, L, Dimou, N., Omiyale, W., Biessy, C., Viallon, V., Kaaks, R., O'Mara, T. A., Aglago, E. K., Ardanaz, E., Bergmann, M. M., Bondonno, N. P., Braaten, T., Colorado-Yohar, S. M., Crous-Bou, M., Dahm, C. C., Fortner, R. T., Gram, I. T., Harlid, S., Heath, A. K., Idahl, A., Kvaskoff, M., Nost, T. H., Overvad, K., Palli, D., Perez-Cornago, A., Sacerdote, C., Sanchez, M. -J., Schulze, M. B., Severi, G., Simeon, V., Tagliabue, G., Tjonneland, A., Truong, T., Tumino, R., Johansson, M., Weiderpass, E., Murphy, N., Gunter, M. J., Lacey, B., Allen, N. E., and Dossus, L.
Subjects: Epidemiology, ESTROGENS, Polymorphism, Single Nucleotide, BREAST, Article, Cigarette Smoking, Risk Factors, GENETIC-VARIANTS, REGRESSION, Humans, Genetic Predisposition to Disease, Prospective Studies, 11 Medical and Health Sciences, INDEX, Cancer och onkologi, IDENTIFICATION, WOMEN, Public Health, Global Health, Social Medicine and Epidemiology, Mendelian Randomization Analysis, Endometrial Neoplasms, OVERLAP, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Oncology, Cancer and Oncology, OBESITY, Female, SEX-HORMONES, Genome-Wide Association Study
Abstract: Background: Current epidemiologic evidence indicates that smoking is associated with a lower endometrial cancer risk. However, it is unknown if this association is causal or confounded. To further elucidate the role of smoking in endometrial cancer risk, we conducted complementary observational and Mendelian randomization (MR) analyses. Methods: The observational analyses included 286,415 participants enrolled in the European Prospective Investigation into Cancer and Nutrition and 179,271 participants in the UK Biobank, and multivariable Cox proportional hazards models were used. In twosampleMR analyses, genetic variants robustly associated with lifetime amount of smoking (n ¼ 126 variants) and ever having smoked regularly (n ¼ 112 variants) were selected and their association with endometrial cancer risk (12,906 cancer/108,979 controls from the Endometrial Cancer Association Consortium) was examined. Results: In the observational analysis, lifetime amount of smoking and ever having smoked regularly were associated with a lower endometrial cancer risk. In the MR analysis accounting for body mass index, a genetic predisposition to a higher lifetime amount of smoking was not associated with endometrial cancer risk (OR per 1-SD increment: 1.15; 95% confidence interval: 0.91–1.44). Genetic predisposition to ever having smoked regularly was not associated with risk of endometrial cancer. Conclusions: Smoking was inversely associated with endometrial cancer in the observational analyses, although unsupported by the MR. Additional studies are required to better understand the possible confounders and mechanisms underlying the observed associations between smoking and endometrial cancer. Impact: The results from this analysis indicate that smoking is unlikely to be causally linked with endometrial cancer risk., World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, NIHR Imperial Biomedical Research Centre (BRC), Danish Cancer Society, Ligue Contre le Cancer (France) Institut Gustave Roussy (France) MutuelleGenerale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe German Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany) Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR), Netherlands Government Netherlands Government, World Cancer Research Fund International (WCRF), Netherlands Government, Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain), Junta de Andalucia, Principality of Asturias Regional Government of Basque Country (Spain) Regional Government of Murcia (Spain) Regional Government of Navarra (Spain) Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society Swedish Research Council County Council of Skane (Sweden) County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) 1000143 MR/M012190/1 MR/N003284/1 MC-UU_12015/1 MC_UU_00006/ 1, Cancer Research UK C864/A14136 C18281/A29019
Published: 2022
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16. Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition

Author: Yammine, S G, Huybrechts, I, Biessy, C, Dossus, L, Panico, S, Sánchez, M J, Benetou, V, Turzanski-Fortner, R, Katzke, V, Idahl, A, Skeie, G, Olsen, K Standahl, Tjønneland, A, Halkjaer, J, Colorado-Yohar, S, Heath, A K, Sonestedt, E, Sartor, H, Schulze, M B, Palli, D, Crous-Bou, M, Dorronsoro, A, Overvad, K, Gurrea, A Barricarte, Severi, G, Vermeulen, R C H, Sandanger, T M, Travis, R C, Key, T, Amiano, P, Van Guelpen, B, Johansson, M, Sund, M, Tumino, R, Wareham, N, Sacerdote, C, Krogh, V, Brennan, P, Riboli, E, Weiderpass, E, Gunter, M J, Chajès, V, IRAS OH Epidemiology Chemical Agents, Apollo - University of Cambridge Repository, Wareham, Nicholas [0000-0003-1422-2993], IRAS OH Epidemiology Chemical Agents, Schulze, M B [0000-0002-0830-5277], and Overvad, K [0000-0001-6429-7921]
Subjects: Cancer Research, Epidemiology, DATABASE, OMEGA-3, Endometrial cancer, MARKERS, Àcids grassos en la nutrició, Risk Factors, Genetics, Humans, Animals, Prospective Studies, gamma-Linolenic Acid, Fatty acids, Epidemiologia, Cancer och onkologi, Fatty acids in human nutrition, Endometrial Neoplasms, Diet, Oncology, Càncer d'endometri, Cancer and Oncology, OBESITY, Female, FISH CONSUMPTION, HEALTH
Abstract: We would like to thank ‘the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands’ for their contribution and ongoing support to the EPIC Study., This work was undertaken during the tenure of a doctoral Fellowship supported by INCa (INCa 2016 − 184), by Fondation ARC pour la recherche sur le cancer (ARC 2019-DOC4) and by IARC. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (C864/A 14136 to EPIC- Norfolk (DOI https://doi.org/10.22025/2019.10.105.00004); C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/N003284/1 and MC_UU_00006/1 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). (United Kingdom)., Data Availability For information on how to submit an application for gaining access to EPIC data and/or biospecimens, please follow the instructions at http://epic.iarc.fr/access/index.php., Background: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. Results: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5-Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. Conclusion: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer., Institut National du Cancer (INCA) France C864/A 14136, Fondation ARC pour la Recherche sur le Cancer ARC 2019-DOC4, IARC, World Health Organization. International Agency for Research on Cancer (IARC), Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, NIHR Imperial Biomedical Research Centre (BRC), Danish Cancer Society, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe. German Cancer Aid, Helmholtz Association, German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund International (WCRF), Netherlands Government, Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vaesterbotten (Sweden), Cancer Research UK C8221/A29017 MR/N003284/1, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MC_UU_00006/1 MR/M012190/1 2016 - 184
Published: 2023
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17. Dietary patterns related to biological mechanisms and survival after breast cancer diagnosis : results from a cohort study

Author: Carlota Castro-Espin, Catalina Bonet, Marta Crous-Bou, Verena Katzke, Charlotte Le Cornet, Franziska Jannasch, Matthias B. Schulze, Anja Olsen, Anne Tjønneland, Christina C. Dahm, Christian S. Antoniussen, Maria Jose Sánchez, Pilar Amiano, María Dolores Chirlaque, Marcela Guevara, Claudia Agnoli, Rosario Tumino, Carlotta Sacerdote, Maria Santucci De Magistris, Malin Sund, Stina Bodén, Torill Enget Jensen, Karina Standahl Olsen, Guri Skeie, Marc J. Gunter, Sabina Rinaldi, Esther M. Gonzalez-Gil, Elisabete Weiderpass, Sofia Christakoudi, Alicia K. Heath, Laure Dossus, and Antonio Agudo
Subjects: Cancer Research, Cancer och onkologi, Nutrition and Dietetics, Breast Neoplasms/diagnosis, Estrogens, Diet, Cohort Studies, Näringslära, Oncology, Risk Factors, Cancer and Oncology, Humans, Female, Prospective Studies
Abstract: BACKGROUND: Inflammatory, insulin and oestrogenic pathways have been linked to breast cancer (BC). We aimed to examine the relationship between pre-diagnostic dietary patterns related to these mechanisms and BC survival. METHODS: The diabetes risk reduction diet (DRRD), inflammatory score of diet (ISD) and oestrogen-related dietary pattern (ERDP) were calculated using dietary data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to assess associations between dietary patterns and overall mortality and competing risk models for associations with BC-specific mortality. RESULTS: We included 13,270 BC cases with a mean follow-up after diagnosis of 8.6 years, representing 2340 total deaths, including 1475 BC deaths. Higher adherence to the DRRD score was associated with lower overall mortality (HR1–SD 0.92; 95%CI 0.87–0.96). Greater adherence to pro-inflammatory diets was borderline associated with 6% higher mortality HR1–SD 1.06; 95%CI 1.00–1.12. No significant association with the oestrogen-related dietary pattern was observed. None of the dietary patterns were associated with BC-specific mortality. CONCLUSIONS: Greater adherence to an anti-diabetic and anti-inflammatory diet prior to diagnosis is associated with lower overall mortality among BC survivors. Long-term adherence to these dietary patterns could be a means to improve the prognosis of BC survivors., Instituto de Salud Carlos III FI19/00197, European Social Fund (ESF), AECC Scientific Foundation PRYES211366AGUD, World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue nationale contre le cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe Helmholtz Association German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR), Dutch Ministry of Public Health, Welfare and Sports (VWS) Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds Netherlands Organization for Scientific Research (NWO), World Cancer Research Fund International (WCRF), Netherlands Government, Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra Navarra, Catalan Institute of Oncology-ICO (Spain), Swedish Cancer Society Swedish Research Council, County Councils of Skkne, Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) 1000143 MR/M012190/1
Published: 2023
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18. Pregnancy outcomes and risk of endometrial cancer

Author: Lauren A. Wise, Jennifer A. Doherty, Harvey A. Risch, Sara H. Olson, Louise A. Brinton, Lynne R. Wilkens, Mengmeng Du, Piet A. van den Brandt, Herbert Yu, Diego Serraino, Carlotta Sacerdote, Malcolm C. Pike, Kirsten B. Moysich, Kristin E. Anderson, Fulvio Ricceri, Timothy R. Rebbeck, Stacey Petruzella, Leo J. Schouten, Elisabete Weiderpass, Amanda B. Spurdle, Renhua Na, Rachael Z. Stolzenberg-Solomon, Fabio Levi, Susan J. Jordan, Christine M. Friedenreich, Fabio Parazzini, Anna E. Prizment, Xiao-Ou Shu, Chu Chen, Lingeng Lu, Todd R. Sponholtz, Thomas E. Rohan, Veronica Wendy Setiawan, Anthony B. Miller, Peggy Reynolds, Penelope M. Webb, Britton Trabert, Vittorio Krogh, Julie R. Palmer, Eva Negri, Wanghong Xu, Gretchen L. Gierach, Marc T. Goodman, Susan E. McCann, Immaculata De Vivo, Hans-Olov Adami, Carlo La Vecchia, Anne Zeleniuch-Jacquotte, Nicolas Wentzensen, Linda S. Cook, J. S. Jordan, R. Na, E. Weiderpa, H. O. Adami, K. E. Anderson, P. A. van den Brandt, L. A. Brinton, C. Chen, L. S. Cook, J. A. Doherty, M. Du, C. M. Friedenreich, G. L. Gierach, M. T. Goodman, V. Krogh, F. Levi, L. Lu, A. B. Miller, S. E. McCann, B. K. Moysich, E. Negri, S. H. Olson, S. Petruzella, J. R. Palmer, F. Parazzini, M. C. Pike, A. E. Prizment, T. R. Rebbeck, P. Reynold, F. Ricceri, H. A. Risch, T. E. Rohan, C. Sacerdote, L. J. Schouten, D. Serraino, V. W. Setiawan, X. -O. Shu, T. R. Sponholtz, A. B. Spurdle, R. Z. Stolzenberg-Solomon, B. Trabert, N. Wentzensen, L. R. Wilken, L. A. Wise, H. Yu, C. La Vecchia, I. De Vivo, W. Xu, A. Zeleniuch-Jacquotte, P. M. Webb, Epidemiologie, and RS: GROW - R1 - Prevention
Subjects: Cancer Research, medicine.medical_specialty, miscarriage, induced abortion, Article, Miscarriage, 03 medical and health sciences, 0302 clinical medicine, AGE, Pregnancy, Risk Factors, Epidemiology, medicine, Humans, HORMONE-BINDING GLOBULIN, REPRODUCTIVE FACTORS, sex of offspring, business.industry, Obstetrics, Endometrial cancer, Pregnancy Outcome, endometrial cancer, parity, WOMEN, Odds ratio, PROGESTERONE, medicine.disease, Confidence interval, Endometrial Neoplasms, 3. Good health, ESTROGEN, Pooled analysis, Oncology, Case-Control Studies, 030220 oncology & carcinogenesis, Cohort, Female, SEX, business
Abstract: A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further similar to 15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.
Published: 2021

19. Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score

Author: Amanda J. Cross, Kristin Benjaminsen Borch, Anne Kirstine Eriksen, Elio Riboli, José María Huerta, H. Bas Bueno-de-Mesquita, Giovanna Masala, Núria Sala, Anne Tjønneland, Anika Hüsing, Rudolf Kaaks, Sara Grioni, Anne M. May, Fanny Artaud, Antonia Trichopoulou, Pilar Amiano, Eleni Peppa, Marc J. Gunter, Timothy J. Key, Aurelio Barricarte Gurrea, Jonna Berntsson, Anna Karakatsani, Mazda Jenab, Elisabete Weiderpass, Isabel Drake, Christina C. Dahm, Torkjel M. Sandanger, Bethany Van Guelpen, Robin Reichmann, María José Sánchez, Guri Skeie, Konstantinos K. Tsilidis, Gianluca Severi, Carlotta Sacerdote, Sjoerd G. Elias, José Ramón Quirós, Marie-Christine Boutron-Ruault, Salvatore Panico, Krasimira Aleksandrova, Rosario Tumino, Sophia Harlid, Elom K. Aglago, [Aleksandrova,K, Reichmann,R] Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Aleksandrova,K, Reichmann,R] Institute of Nutritional Science, University of Potsdam, Potsdam, Germany. [Aleksandrova,K] Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany. [Kaaks,R, Hüsing,A] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Jenab,M, Weiderpass,E, Aglago,EK, Gunter,MJ] International Agency for Research on Cancer, World Health Organization, Lyon, France. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Cross,AJ, Tsilidis,KK, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Dahm,CC] Department of Public Health, Aarhus University, Aarhus, Denmark. [Eriksen,AK, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Artaud,F, Boutron-Ruault,MC, Severi,G] CESP, Faculté de Medicine, Université Paris-Saclay, Villejuif, France. [Artaud,F, Severi,G] Institut Gustave Roussy, Villejuif, France. [Severi,G] Dipartimento di Statistica, Informatica e Applicazioni 'G. Parenti' (DISIA), University of Florence, Florence, Italy. [Trichopoulou,A, Karakatsani,A, Peppa,E] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, 'ATTIKON' University Hospital, Haidari, Greece. [Panico,S] EPIC Centre of Naples, Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Naples, Italy. [Masala,G] 1Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy. [Grioni,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy. [Tumino,R] Cancer Registry and Histopathology Department, Provincial Health Authority (ASP), Ragusa, Italy. [Elias,SG, May,AM] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. [Borch,KB, Sandanger,TM, Skeie,G] Department of Community Medicine, Health Faculty, UiT-the Arctic university of Norway, Tromsø, Norway. [Sánchez,MJ] Escuela Andaluza de Salud Pública (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Sánchez,MJ, Huerta,JM, Gurrea,AB, Amiano,P] Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Sánchez,MJ] Universidad de Granada, Granada, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Sala,N] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Translational Research Laboratory, Catalan Institute of Oncology (ICO), Barcelona, Spain. [Sala,N] Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. [Gurrea,AB] Navarra Public Health Institute, Pamplona, Spain. [Gurrea,AB] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Amiano,P] Ministry of Health of the Basque Government, Public Health Division of Gipuzkoa, Biodonostia Health Research Institute, Donostia-San Sebastian, Spain. [Berntsson,J] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. [Drake,I] Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden. [van Guelpen,B, Harlid,S] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Key,T] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., This work was supported by the German Research Foundation (DFG) (grant AL 1784/3-1), which funded the research position of Dr. Aleksandrova for organizing study conduct and analysis. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) and Federal Ministry of Education and Research (BMBF) (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS), Instituto de salud Carlos III PI13/00061 to Granada, PI13/ 01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra and Catalonia (Catalan Institute of Oncology – ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (C864/A14136 to EPIC-Norfolk and C8221/A19170 to EPICOxford), Medical Research Council (MR/N003284/1 and MC-UU_12015/1 to EPIC-Norfolk and MR/M012190/1 to EPIC-Oxford) (United Kingdom). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Open Access funding enabled and organized by Projekt DEAL.
Subjects: Male, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk::Risk Assessment [Medical Subject Headings], lcsh:Medicine, Cancer prevention, Cohort Studies, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Calibration [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Neoplasias colorrectales, Medicine, 030212 general & internal medicine, Prospective Studies, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings], 10. No inequality, Prospective cohort study, 11 Medical and Health Sciences, Framingham Risk Score, Risk screening, Lifestyle behaviour, Risk prediction, Colorectal cancer, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030220 oncology & carcinogenesis, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies [Medical Subject Headings], Female, Risk assessment, Colorectal Neoplasms, Research Article, Cohort study, Estils de vida, Waist, Lifestyles, Nutritional Status, Check Tags::Male [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Estil de vida, Risk Assessment, Riesgo, Estilo de vida, 03 medical and health sciences, Càncer colorectal, General & Internal Medicine, Humans, Life Style, business.industry, lcsh:R, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk [Medical Subject Headings], Technology and Food and Beverages::Food and Beverages::Food::Vegetables [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], Nomogram, Lifestyle, Diet, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Check Tags::Female [Medical Subject Headings], Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::Exercise [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], business, Prevención de Enfermedades, Demography
Abstract: Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level., German Research Foundation (DFG) AL 1784/3-1, European Commission European Commission Joint Research Centre, International Agency for Research on Cancer, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) (Germany), Federal Ministry of Education & Research (BMBF), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro (AIRC), Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Instituto de Salud Carlos III PI13/00061 PI13/01162, Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain) 6236, Regional Government of Navarra (Spain), Regional Government of Catalonia (Catalan Institute of Oncology -ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK C864/A14136 C8221/A19170, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/N003284/1 MC-UU_12015/1 MR/M012190/1, Projekt DEAL
Published: 2021
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20. Are Circulating Immune Cells a Determinant of Pancreatic Cancer Risk? A Prospective Study Using Epigenetic Cell Count Measures

Author: Matthias B. Schulze, Anne Tjønneland, Laure Dossus, Sofia Christakoudi, Kim Overvad, Verena Katzke, Roel Vermeulen, Giovanna Masala, Pilar Amiano, Elisabete Weiderpass, José María Huerta, Anja Olsen, Federico Canzian, Valeria Pala, Theron Johnson, Oskar Franklin, Charlotte Le Cornet, Marie-Christine Boutron-Ruault, Salvatore Panico, Eva Ardanaz, Rosario Tumino, Esther Molina-Montes, Bas Bueno-de-Mesquita, Marta Crous-Bou, Sven Olek, Rayaan Mahfouz, Rudolf Kaaks, Aurora Perez-Cornago, Bianca Brauer, Gianluca Severi, Carlotta Sacerdote, Vinciane Rebours, and Malin Sund
Subjects: Adult, Male, Neutrophils, Epidemiology, Lymphocyte, pancreatic cancer, T-Lymphocytes, Regulatory, Epigenesis, Genetic, Immune system, neutrophils, Pancreatic cancer, Biomarkers, Tumor, Humans, T-lymphocyte subsets, Cytotoxic T cell, Medicine, Lymphocyte Count, Prospective Studies, Prospective cohort study, Aged, Aged, 80 and over, business.industry, FOXP3, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Causality, Pancreatic Neoplasms, EPIC study, immune system, medicine.anatomical_structure, Oncology, Case-Control Studies, Immunology, Female, business, CD8
Abstract: Background: Evidence is accumulating that immune cells play a prominent role in pancreatic cancer etiology but prospective investigations are missing. Methods: We conducted a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study with 502 pairs of incident pancreatic cancer cases and matched controls. Relative counts of circulating immune cells (neutrophils and lymphocyte sublineages: total CD3+, CD8+, CD4+, and FOXP3+ regulatory T cells (Tregs) relative to nucleated cells, (white blood cells) were measured by qRT-PCR. ORs with 95% confidence intervals were estimated using logistic regressions, modeling relative counts of immune cells on a continuous scale. Results: Neither relative counts of immune cell types taken individually, nor mutually adjusted for each other were associated with pancreatic cancer risks. However, in subgroup analyses by strata of lag-time, higher relative counts of Tregs and lower relative counts of CD8+ were significantly associated with an increased pancreatic cancer risks in participants diagnosed within the first 5 years of follow-up. Conclusions: These results might reflect reverse causation, due to higher relative counts of Tregs and lower counts of CD8+ cells among individuals with more advanced stages of latent pancreatic cancer, who are closer to the point of developing clinical manifest disease. Impact: We have shown, for the first time, that increased relative counts of regulatory T cells and lower relative counts of CD8+, cytotoxic T cells may be associated with pancreatic cancer risk or relatively late-stage tumor development. See related commentary by Michaud and Kelsey, p. 2176
Published: 2021
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21. Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer

Author: Trasias Mukama, Renée Turzanski Fortner, Verena Katzke, Lucas Cory Hynes, Agnese Petrera, Stefanie M. Hauck, Theron Johnson, Matthias Schulze, Catarina Schiborn, Agnetha Linn Rostgaard-Hansen, Anne Tjønneland, Kim Overvad, María José Sánchez Pérez, Marta Crous-Bou, María-Dolores Chirlaque, Pilar Amiano, Eva Ardanaz, Eleanor L. Watts, Ruth C. Travis, Carlotta Sacerdote, Sara Grioni, Giovanna Masala, Simona Signoriello, Rosario Tumino, Inger T. Gram, Torkjel M. Sandanger, Hanna Sartor, Eva Lundin, Annika Idahl, Alicia K. Heath, Laure Dossus, Elisabete Weiderpass, Rudolf Kaaks, Mukama, T., Fortner, R. T., Katzke, V., Hynes, L. C., Petrera, A., Hauck, S. M., Johnson, T., Schulze, M., Schiborn, C., Rostgaard-Hansen, A. L., Tjonneland, A., Overvad, K., Perez, M. J. S., Crous-Bou, M., Chirlaque, M. -D., Amiano, P., Ardanaz, E., Watts, E. L., Travis, R. C., Sacerdote, C., Grioni, S., Masala, G., Signoriello, S., Tumino, R., Gram, I. T., Sandanger, T. M., Sartor, H., Lundin, E., Idahl, A., Heath, A. K., Dossus, L., Weiderpass, E., and Kaaks, R.
Subjects: Ovarian Neoplasms, Cancer Research, Cancer och onkologi, Science & Technology, endocrine system diseases, Membrane Proteins, Blood Proteins, Carcinoma, Ovarian Epithelial, female genital diseases and pregnancy complications, 1117 Public Health and Health Services, ADAM Proteins, Oncology, ROC Curve, CA-125 Antigen, Case-Control Studies, Cancer and Oncology, Biomarkers, Tumor, Humans, TRIAL, Female, Folate Receptor 1, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Life Sciences & Biomedicine, Early Detection of Cancer
Abstract: The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London-, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra,-and the Catalan Institute of OncologyICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (C864/A14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/N003284/1, MC-UU 12015/1 and MC UU_00006/1to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). (United Kingdom). Open Access funding enabled and organized by Projekt DEAL., BACKGROUND: CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer. METHODS: In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer. RESULTS: Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancerfree. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9–18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone. CONCLUSION: Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0–9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125., World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, German Cancer Research Center (DKFZ) (Germany), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII) (Spain), Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), Catalan Institute of OncologyICO (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK C864/A14136 C8221/A29017, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) MR/N003284/1 MC-UU 12015/1 MC UU_00006/1 MR/M012190/1, Projekt DEAL
Published: 2022
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22. Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies

Author: Pierre-Antoine Dugué, Clara Bodelon, Felicia F. Chung, Hannah R. Brewer, Srikant Ambatipudi, Joshua N. Sampson, Cyrille Cuenin, Veronique Chajès, Isabelle Romieu, Giovanni Fiorito, Carlotta Sacerdote, Vittorio Krogh, Salvatore Panico, Rosario Tumino, Paolo Vineis, Silvia Polidoro, Laura Baglietto, Dallas English, Gianluca Severi, Graham G. Giles, Roger L. Milne, Zdenko Herceg, Montserrat Garcia-Closas, James M. Flanagan, Melissa C. Southey, Monash University [Clayton], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, National Institutes of Health, NIH, National Cancer Institute, NCI, Breast Cancer Now, BCN, Division of Cancer Epidemiology and Genetics, National Cancer Institute, DCEG, European Commission, EC, National Health and Medical Research Council, NHMRC: 1011618, 1164455, Fondation ARC pour la Recherche sur le Cancer, ARC, Ligue Contre le Cancer, Seventh Framework Programme, FP7, Institut National Du Cancer, INCa, Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization., This research was partially supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. The work performed by the Epigenomics and Mechanisms Branch at IARC was supported by grants from the Institut National du Cancer (INCa, France), the European Commission (EC) Seventh Framework Programme (FP7) Translational Cancer Research (TRANSCAN) Framework, the Fondation ARC pour la Recherche sur le Cancer (France), and la Ligue Nationale (Française) Contre le Cancer to ZH. The MCCS methylation work was supported by the National Health and Medical Research Council (grant numbers 1011618 and 1164455) and the Victorian Breast Cancer Research Consortium. The work performed at Imperial College London was funded by Breast Cancer Now and supported by the Cancer Research UK Imperial Centre, the National Institute for Health Research Imperial Biomedical Research Centre and the Ovarian Cancer Action Research Centre. MCS is a National Health and Medical Research Council Senior Research Fellow (GNT1155163)., and HAL UVSQ, Équipe
Subjects: Aging, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, DNA Methylation, Lifestyle, Epigenesis, Genetic, Epigenetic aging, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Prospective study DNA methylation Epigenetic aging Lifestyle Breast cancer risk, Humans, Female, Prospective Studies, Prospective study, Breast cancer risk, Life Style
Abstract: Background DNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including cancer. Here we aimed to study epigenetic measures of aging and lifestyle-related factors in association with risk of breast cancer. Methods Using data from four prospective case–control studies nested in three cohorts of European ancestry participants, including a total of 1,655 breast cancer cases, we calculated three methylation-based measures of lifestyle factors (body mass index [BMI], tobacco smoking and alcohol consumption) and seven measures of epigenetic aging (Horvath-based, Hannum-based, PhenoAge and GrimAge). All measures were regression-adjusted for their respective risk factors and expressed per standard deviation (SD). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional or unconditional logistic regression and pooled using fixed-effects meta-analysis. Subgroup analyses were conducted by age at blood draw, time from blood sample to diagnosis, oestrogen receptor-positivity status and tumour stage. Results None of the measures of epigenetic aging were associated with risk of breast cancer in the pooled analysis: Horvath ‘age acceleration’ (AA): OR per SD = 1.02, 95%CI: 0.95–1.10; AA-Hannum: OR = 1.03, 95%CI:0.95–1.12; PhenoAge: OR = 1.01, 95%CI: 0.94–1.09 and GrimAge: OR = 1.03, 95%CI: 0.94–1.12, in models adjusting for white blood cell proportions, body mass index, smoking and alcohol consumption. The BMI-adjusted predictor of BMI was associated with breast cancer risk, OR per SD = 1.09, 95%CI: 1.01–1.17. The results for the alcohol and smoking methylation-based predictors were consistent with a null association. Risk did not appear to substantially vary by age at blood draw, time to diagnosis or tumour characteristics. Conclusion We found no evidence that methylation-based measures of aging, smoking or alcohol consumption were associated with risk of breast cancer. A methylation-based marker of BMI was associated with risk and may provide insights into the underlying associations between BMI and breast cancer.
Published: 2022
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23. Association of Pre-diagnostic Antibody Responses to Escherichia coli and Bacteroides fragilis Toxin Proteins with Colorectal Cancer in a European Cohort

Author: Christina C. Dahm, Inger T. Gram, Elom K. Aglago, Eva Ardanaz, Bas Bueno-de-Mesquita, Krasimira Aleksandrova, David J. Hughes, Joseph A. Rothwell, Anja Olsen, Renée Turzanski-Fortner, Elisabete Weiderpass, Mazda Jenab, Valeria Pala, R. Tumino, Marie-Christine Boutron-Ruault, Thyra Löwenmark, Semi Zouiouich, María Dolores Chirlaque, Rudolf Kaaks, Gianluca Severi, Carlotta Sacerdote, Jill Werner, Carla H. van Gils, Marko Lukic, Salvatore Panico, Richard Palmquist, Heinz Freisling, Ruth C. Travis, Matthias B. Schulze, Núria Sala, Tim Waterboer, María José Pérez, Amanda J. Cross, Alicia K Heath, Julia Butt, Veronika Fedirko, Domenico Palli, and Anne Tjønneland
Subjects: 0301 basic medicine, Male, Colorectal cancer, serology, RC799-869, medicine.disease_cause, Serology, Bacteroides fragilis, 0302 clinical medicine, Odds Ratio, Prospective Studies, Escherichia coli Infections, Gastroenterology, food and beverages, Metalloendopeptidases, Diseases of the digestive system. Gastroenterology, Middle Aged, Bacteroides Infections, Antibodies, Bacterial, Europe, Prospective, Infectious Diseases, bacteroides fragilis, Cohort, 030211 gastroenterology & hepatology, Female, Colorectal Neoplasms, 0605 Microbiology, Research Article, Research Paper, Microbiology (medical), Adult, Colon, Bacterial Toxins, Gastroenterology and Hepatology, Biology, Microbiology, 03 medical and health sciences, Càncer colorectal, medicine, Gastroenterologi, Escherichia coli, Biomarkers, Tumor, Humans, VDP::Medisinske Fag: 700, Bacteroides fragilis toxin, Aged, Antigens, Bacterial, Bacils, prospective, medicine.disease, biology.organism_classification, VDP::Medical disciplines: 700, Bacillus (Bacteria), 030104 developmental biology, Antibody response, Escheríchia coli
Abstract: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); the Sicilian Government, AIRE ONLUS Ragusa, AVIS Ragusa, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands); Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barcelona), Spain; Swedish Cancer Society, Swedish Scientific Council, and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (C864/A14136 to EPIC-Norfolk; C8221/A19170, C570/A16491 and C8221/ A290170 to EPIC-Oxford), Medical Research Council (MR/ N003284/1 and MC-UU_12015/1 to EPIC-Norfolk, MR/ M012190/1 to EPIC-Oxford (UK). The funding sources had no influence on the design of the study; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the paper for publication.Support for this study was also provided by the COST Action CA17118 supported by COST (European Cooperation in Science and Technology, www.cost.eu) to DJH., Experimental evidence has implicated genotoxic Escherichia coli (E. coli) and enterotoxigenic Bacteroides fragilis (ETBF) in the development of colorectal cancer (CRC). However, evidence from epidemiological studies is sparse. We therefore assessed the association of serological markers of E. coli and ETBF exposure with odds of developing CRC in the European Prospective Investigation into Nutrition and Cancer (EPIC) study. Serum samples of incident CRC cases and matched controls (n = 442 pairs) were analyzed for immunoglobulin (Ig) A and G antibody responses to seven E. coli proteins and two isoforms of the ETBF toxin via multiplex serology. Multivariable-adjusted conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of sero-positivity to E. coli and ETBF with CRC. The IgA-positivity of any of the tested E. coli antigens was associated with higher odds of developing CRC (OR: 1.42; 95% CI: 1.05–1.91). Dual-positivity for both IgA and IgG to E. coli and ETBF was associated with >1.7-fold higher odds of developing CRC, with a significant association only for IgG (OR: 1.75; 95% CI: 1.04, 2.94). This association was more pronounced when restricted to the proximal colon cancers (OR: 2.62; 95% CI: 1.09, 6.29) compared to those of the distal colon (OR: 1.24; 95% CI: 0.51, 3.00) (pheterogeneity = 0.095). Sero-positivity to E. coli and ETBF was associated with CRC development, suggesting that co-infection of these bacterial species may contribute to colorectal carcinogenesis. These findings warrant further exploration in larger prospective studies and within different population groups., European Commission (DG-SANCO), International Agency for Research on Cancer, Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Sicilian Government, AIRE ONLUS Ragusa, AVIS Ragusa, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barcelona), Spain, Swedish Cancer Society, Swedish Scientific Council, and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (C864/A14136 to EPIC-Norfolk; C8221/A19170, C570/A16491 and C8221/ A290170 to EPIC-Oxford), Medical Research Council (MR/ N003284/1 and MC-UU_12015/1 to EPIC-Norfolk, MR/ M012190/1 to EPIC-Oxford (UK), COST Action CA17118 supported by COST (European Cooperation in Science and Technology)
Published: 2021
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24. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe

Author: Hageman, S., Pennells, L., Ojeda, F., Kaptoge, S., Kuulasmaa, K., Vries, T. de, Xu, Z., Kee, F., Chung, R., Wood, A., McEvoy, J.W., Veronesi, G., Bolton, T., Dendale, P., Ference, B.A., Halle, M., Timmis, A., Vardas, P., Danesh, J., Graham, I., Salomaa, V., Visseren, F., Bacquer, D. de, Blankenberg, S., Dorresteijn, J., Angelantonio, E. di, Achenbach, S., Aleksandrova, K., Amiano, P., Amouyel, P., Andersson, J., Bakker, S.J.L., Costa, R.B.D., Beulens, J.W.J., Blaha, M., Bobak, M., Boer, J.M.A., Bonet, C., Bonnet, F., Boutron-Ruault, M.C., Braaten, T., Brenner, H., Brunner, F., Brunner, E.J., Brunstrom, M., Buring, J., Butterworth, A.S., Capkova, N., Cesana, G., Chrysohoou, C., Colorado-Yohar, S., Cook, N.R., Cooper, C., Dahm, C.C., Davidson, K., Dennison, E., Castelnuovo, A. di, Donfrancesco, C., Dorr, M., Dorynska, A., Eliasson, M., Engstrom, G., Ferrari, P., Ferrario, M., Ford, I., Fu, M., Gansevoort, R.T., Giampaoli, S., Gillum, R.F., Camara, A.G. de la, Grassi, G., Hansson, P.O., Huculeci, R., Hveem, K., Iacoviello, L., Ikram, M.K., Jorgensen, T., Joseph, B., Jousilahti, P., Jukema, J.W., Kaaks, R., Katzke, V., Kavousi, M., Kiechl, S., Klotsche, J., Konig, W., Kronmal, R.A., Kubinova, R., Kucharska-Newton, A., Lall, K., Lehmann, N., Leistner, D., Linneberg, A., Pablos, D.L., Lorenz, T., Lu, W.T., Luksiene, D., Lyngbakken, M., Magnussen, C., Malyutina, S., Ibanez, A.M., Masala, G., Mathiesen, E.B., Matsushita, K., Meade, T.W., Melander, O., Meyer, H.E., Moons, K.G.M., Moreno-Iribas, C., Muller, D., Munzel, T., Nikitin, Y., Nordestgaard, B.G., Omland, T., Onland, C., Overvad, K., Packard, C., Pajak, A., Palmieri, L., Panagiotakos, D., Panico, S., Perez-Cornago, A., Peters, A., Pietila, A., Pikhart, H., Psaty, B.M., Quarti-Trevano, F., Garcia, J.R.Q., Riboli, E., Ridker, P.M., Rodriguez, B., Rodriguez-Barranco, M., Rosengren, A., Roussel, R., Sacerdote, C., Sans, S., Sattar, N., Schiborn, C., Schmidt, B., Schottker, B., Schulze, M., Schwartz, J.E., Selmer, R.M., Shea, S., Shipley, M.J., Sieri, S., Soderberg, S., Sofat, R., Tamosiunas, A., Thorand, B., Tillmann, T., Tjonneland, A., Tong, T.Y.N., Trichopoulou, A., Tumino, R., Tunstall-Pedoe, H., Tybjaerg-Hansen, A., Tzoulaki, J., Heijden, A. van der, Schouw, Y.T. van der, Verschuren, W.M.M., Volzke, H., Waldeyer, C., Wareham, N.J., Weiderpass, E., Weidinger, F., Wild, P., Willeit, J., Willeit, P., Wilsgaard, T., Woodward, M., Zeller, T., Zhang, D.D., Zhou, B., SCORE2 Working Grp, ESC Cardiovasc Risk Collaboration, collaboration, SCORE2 working group and ESC Cardiovascular risk, Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Epidemiology, Neurology, Achenbach, S, Aleksandrova, K, Amiano, P, San Sebastian, D, Amouyel, P, Andersson, J, Bakker, S, Da Providencia Costa, R, Beulens, J, Blaha, M, Bobak, M, Boer, J, Bonet, C, Bonnet, F, Boutron-Ruault, M, Braaten, T, Brenner, H, Brunner, F, Brunner, E, Brunström, M, Buring, J, Butterworth, A, Capkova, N, Cesana, G, Chrysohoou, C, Colorado-Yohar, S, Cook, N, Cooper, C, Dahm, C, Davidson, K, Dennison, E, Di Castelnuovo, A, Donfrancesco, C, Dörr, M, Doryńska, A, Eliasson, M, Engström, G, Ferrari, P, Ferrario, M, Ford, I, Fu, M, Gansevoort, R, Giampaoli, S, Gillum, R, Gómez de la Cámara, A, Grassi, G, Hansson, P, Huculeci, R, Hveem, K, Iacoviello, L, Ikram, M, Jørgensen, T, Joseph, B, Jousilahti, P, Wouter Jukema, J, Kaaks, R, Katzke, V, Kavousi, M, Kiechl, S, Klotsche, J, König, W, Kronmal, R, Kubinova, R, Kucharska-Newton, A, Läll, K, Lehmann, N, Leistner, D, Linneberg, A, Pablos, D, Lorenz, T, Lu, W, Luksiene, D, Lyngbakken, M, Magnussen, C, Malyutina, S, Ibañez, A, Masala, G, Mathiesen, E, Matsushita, K, Meade, T, Melander, O, Meyer, H, Moons, K, Moreno-Iribas, C, Muller, D, Münzel, T, Nikitin, Y, Nordestgaard, B, Omland, T, Onland, C, Overvad, K, Packard, C, Pająk, A, Palmieri, L, Panagiotakos, D, Panico, S, Perez-Cornago, A, Peters, A, Pietilä, A, Pikhart, H, Psaty, B, Quarti-Trevano, F, Garcia, J, Riboli, E, Ridker, P, Rodriguez, B, Rodriguez-Barranco, M, Rosengren, A, Roussel, R, Sacerdote, C, S, S, Sattar, N, Schiborn, C, Schmidt, B, Schöttker, B, Schulze, M, Schwartz, J, Selmer, R, Shea, S, Shipley, M, Sieri, S, Söderberg, S, Sofat, R, Tamosiunas, A, Thorand, B, Tillmann, T, Tjønneland, A, Tong, T, Trichopoulou, A, Tumino, R, Tunstall-Pedoe, H, Tybjaerg-Hansen, A, Tzoulaki, J, van der Heijden, A, van der Schouw, Y, Verschuren, W, Völzke, H, Waldeyer, C, Wareham, N, Weiderpass, E, Weidinger, F, Wild, P, Willeit, J, Willeit, P, Wilsgaard, T, Woodward, M, Zeller, T, Zhang, D, Zhou, B, and Apollo - University of Cambridge Repository
Subjects: Male, Cardiology, RATIONALE, Blood Pressure, Disease, 030204 cardiovascular system & hematology, PROFILE, ACUTE CORONARY EVENTS, VALIDATION, Europe/epidemiology, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, DESIGN, Clinical Research, Risk Factors, Diabetes mellitus, medicine, PARTICIPANTS, Humans, 030212 general & internal medicine, Risk factor, Aged, Primary prevention, business.industry, 10-year CVD risk, Incidence (epidemiology), Cardiovascular Diseases/epidemiology, Risk Prediction, Cardiovascular Disease, Primary Prevention, 10-year Cvd Risk, External validation, PRIMARY-CARE, Middle Aged, medicine.disease, Cardiovascular disease, Risk prediction, 3. Good health, Europe, Prediction algorithms, Blood pressure, Cardiovascular Diseases, Smoking status, Female, Cardiology and Cardiovascular Medicine, business, Algorithms, Demography
Abstract: Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe.Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries.Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe. Acknowledgements We thank investigators and participants of the several studies that contributed data to the Emerging Risk Factors Collaboration (ERFC). This research has been conducted using the UK Biobank Resource under Application Number 26865. Data from the Clinical Practice Research Datalink (CPRD) were obtained under licence from the UK Medicines and Healthcare products Regulatory Agency (protocol 162RMn2). CPRD uses data provided by patients and collected by the NHS as part of their care and support. We thank all EPIC participants and staff for their contribution to the study, the laboratory teams at the Medical Research Council Epidemiology Unit for sample management and Cambridge Genomic Services for genotyping, Sarah Spackman for data management and the team at the EPIC-CVD Coordinating Centre for study co-ordination and administration. Funding The ERFC co-ordinating centre was underpinned by programme grants from the British Heart Foundation (SP/09/002; RG/13/13/30194; RG/18/13/33946), BHF Centre of Research Excellence (RE/18/1/34212), the UK Medical Research Council (MR/L003120/1), and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC1215-20014), with project-specific support received from the UK NIHR [*], British United Provident Association UK Foundation and an unrestricted educational grant from GlaxoSmithKline. A variety of funding sources have supported recruitment, follow-up, and laboratory measurements in the studies contributing data to the ERFC, which are listed on the ERFC website (www.phpc.cam.ac.uk/ceu/erfc/list-of-studies). *The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome. The MORGAM Project has received funding from EU projects MORGAM (Biomed BMH4-CT98-3183), GenomEUtwin (FP5, QLG2-CT-2002-01254), ENGAGE (FP7, HEALTH-F4-2007-201413),CHANCES (FP7, HEALTH-F3-2010-242244), BiomarCaRE (FP7,HEALTH-F2-2011-278913), euCanSHare (Horizon 2020, No. 825903) and AFFECT-EU (Horizon 2020, No. 847770); and Medical Research Council, London (G0601463, No. 80983: Biomarkers in the MORGAM Populations). This has supported central coordination, workshops and part of the activities of the MORGAM Data Centre, the MORGAM Laboratories and the MORGAM Participating Centres EPIC-CVD was funded by the European Research Council (268834), and the European Commission Framework Programme 7 (HEALTH-F2-2012-279233). This work was supported by the Estonian Research Council grant PUTs (PRG687, PUT1660, PUT1665, PRG184), by European Union through the European Regional Development Fund project no. MOBERA5 (Norface Network project no 462.16.107), by the Green ICT programme under Norway Grants 2014 – 2021 (grant number EU53928), by the European Union through Horizon 2020 grant no. 810645 and through the European Regional Development Fund (Project No. 2014-2020.4.01.16-0125) and by the PRECISE4Q consortium. PRECISE4Q project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant agreement 777107. This work was partly funded through the CoMorMent project. CoMorMent has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant agreement 847776. The KORA study was initiated and financed by the Helmholtz Zentrum Mu¨nchen—German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. The KORA study was supported by a research grant from the Virtual Institute of Diabetes Research (Helmholtz Zentrum Mu¨nchen), the Clinical Cooperation Group Diabetes between Ludwig-Maximilians-Universita¨t Mu¨nchen and Helmholtz Zentrum Mu¨nchen, and by the German Diabetes Center (DDZ). The HAPIEE project, Institute, was supported by grants from the Wellcome Trust (064947/Z/01/Z; WT081081) and US National Institute on Aging (1R01 and AG23522). The co-ordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Ge´ne´rale de l’Education Nationale, Institut National de la Sante´ et de la Recherche Me´dicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch 2448 SCORE2 working group and ESC Cardiovascular Risk Collaboration Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucı´a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology—ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Ska˚ne and Va¨sterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom)
Published: 2021
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25. Health status assessment of a population of asylum seekers in Northern Italy

Author: Luca Manfredi, Veronica Sciannameo, Cinzia Destefanis, Marta Prisecaru, Giorgia Cossu, Roberto Gnavi, Alessandra Macciotta, Alberto Catalano, Roberto Raffaele Pepe, Carlotta Sacerdote, and Fulvio Ricceri
Subjects: Adult, Male, Refugees, Adolescent, Asylum seekers, Health Status, Health Policy, Public Health, Environmental and Occupational Health, Migrants diseases, Migrants health, Migration, Migration in Italy, Africa South of the Sahara, Cross-Sectional Studies, Female, Humans, Italy, Retrospective Studies, Young Adult
Abstract: Background Since 2011 Italy has faced an extraordinary increase in migrants arrivals, mainly from the Mediterranean route, one of the world’s most dangerous journeys. The purpose of the present article is to provide a comprehensive picture of the migrants' health status in the "T. Fenoglio" centre, Settimo Torinese (Turin, Italy). Methods A retrospective cross-sectional study was conducted using data collected from June 2016 to May 2018 on adult migrants (over 18 years old) from Africa, Middle East and South East Asia (Bangladesh, Cambodia, India, Nepal). Data was collected through the migrants' medical records. Descriptive statistics were performed on socio-demographic variables. The diagnosed diseases were anonymously registered and classified according to the International Classification of Primary Care (ICPC-2). Conditional Inference Trees were used to perform a descriptive analysis of the sample and to detect the covariates with the strongest association with the variables Disease on arrival, Disease after arrival, ICPC on arrival and ICPC after arrival. Results Analyzed observations were 9 857. 81.8% were men, median age was 23 (Interquartile range: 20.0–27.4). 70.3% of the sample came from Sub-Saharan Africa. 2 365 individuals (24%) arrived at the centre with at least one disease. On arrival, skin (27.71%), respiratory (14.46%), digestive (14.73%) and generic diseases (20.88%) were the most frequent. During the stay respiratory diseases were the most common (25.70%). The highest probability of arriving with a disease occurred in 2018 and during the period September–November 2016, in particular for people from the Horn of Africa. During this period and also in the first half of 2017, skin diseases were the most reported. In seasons with lower prevalence of diseases on arrival the most common disease code was generic for both men and women (usually fever or trauma). Conclusions This study provides information on the diverse diseases that affect the asylum seekers population. In our sample, the Horn of Africa was the most troubled area of arrival, with severe conditions frequently reported regarding skin diseases, in particular scabies. 2018 was the most critical year, especially for migrants from the Horn of Africa and Sub-Saharan Africa. During the stay at the camp, the prevalence of respiratory diseases increased. However, skin diseases remained the main issue for people from the Horn of Africa. Overall, the most reported diseases in the sample were dermatological, respiratory, digestive and generic diseases, both on arrival and during the stay. A better understanding of the health status of asylum seekers is an important factor to determine a more efficient reception and integration process and a better allocation of economic resources in the context of migrants' health care.
Published: 2022
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26. Dietary intakes of dioxins and polychlorobiphenyls (PCBs) and breast cancer risk in 9 European countries

Author: Thibault Fiolet, Corinne Casagrande, Geneviève Nicolas, Zsuzsanna Horvath, Pauline Frenoy, Elisabete Weiderpass, Verena Katzke, Rudolf Kaaks, Miguel Rodriguez-Barranco, Salvatore Panico, Carlotta Sacerdote, Jonas Manjer, Emily Sonestedt, Sara Grioni, Antonio Agudo, Charlotta Rylander, Therese Haugdahl Nøst, Guri Skeie, Anne Tjønneland, Ole Raaschou-Nielsen, Eva Ardanaz, Pilar Amiano, María Dolores Chirlaque López, Matthias B. Schulze, Maria Wennberg, Sophia Harlid, Manon Cairat, Marina Kvaskoff, Inge Huybrechts, and Francesca Romana Mancini
Subjects: Adult, Male, Breast Neoplasms/epidemiology, Breast Neoplasms, Food Contamination, Occupational Health and Environmental Health, Middle Aged, Dioxins, Polychlorinated Biphenyls, Càncer de mama, Diet, Alimentació, Persistent pollutants, Eating, Arbetsmedicin och miljömedicin, Polychlorobiphenyls, Dioxins/adverse effects, Breast cancer, Polychlorinated Biphenyls/adverse effects, Food Contamination/analysis, Humans, Female, Prospective Studies, PCBs, General Environmental Science
Abstract: Background: Dioxins and polychlorobiphenyls (PCBs) are persistent organic pollutants that have demonstrated endocrine disrupting properties. Several of these chemicals are carcinogenic and positive associations have been suggested with breast cancer risk. In general population, diet represents the main source of exposure. Methods: Associations between dietary intake of 17 dioxins and 35 PCBs and breast cancer were evaluated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries using multivariable Cox regressions. The present study included 318,607 women (mean ± SD age: 50.7 ± 9.7) with 13,241 incident invasive breast cancers and a median follow-up of 14.9 years (IQR = 13.5–16.4). Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with food contamination data provided by the European Food Safety Authority. Results: Exposure to dioxins, dioxins + Dioxin-Like-PCBs, Dioxin-Like-PCBs (DL-PCBs), and Non-Dioxin-LikePCBs (NDL-PCBs) estimated from reported dietary intakes were not associated with breast cancer incidence, with the following hazard ratios (HRs) and 95% confidence intervals for an increment of 1 SD: HRdioxins = 1.00 (0.98 to 1.02), HRdioxins+DL-PCB = 1.01 (0.98 to 1.03), HRL-PCB = 1.01 (0.98 to 1.03), and HRNDL-PCB = 1.01 (0.99 to 1.03). Results remained unchanged when analyzing intakes as quintile groups, as well as when analyses were run separately per country, or separating breast cancer cases based on estrogen receptor status or after further adjustments on main contributing food groups to PCBs and dioxins intake and nutritional factors. Conclusions: This large European prospective study does not support the hypothesis of an association between dietary intake of dioxins and PCBs and breast cancer risk.
Published: 2022
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27. Reducing socio-economic inequalities in all-cause mortality: a counterfactual mediation approach

Author: Marcel Goldberg, Graham G. Giles, Jessica E. Laine, Cyrille Delpierre, Salvatore Panico, Henrique Barros, Martina Gandini, Pierre Antoine Dugué, Gianluca Severi, Marie Zins, Paolo Vineis, Roger L. Milne, Silvia Stringhini, Allison M. Hodge, Carlotta Sacerdote, Valéria Troncoso Baltar, Marc Chadeau-Hyam, Rosario Tumino, Mika Kivimäki, Vittorio Krogh, Vittorio Perduca, LIFEPATH Consortium, Alenius, H., Avendano, M., Baltar, V., Bartley, M., Barros, H., Bochud, M., Carmeli, C., Carra, L., Castagné, R., Chadeau-Hyam, M., Clavel-Chapelon, F.O., Costa, G., Courtin, E., Delpierre, C., Donkin, A., D'Errico, A., Dugué, P.A., Elliott, P., Fiorito, G., Fraga, S., Garès, V., Gandini, M., Giles, G., Goldberg, M., Greco, D., Hodge, A., Karimi, M., Kelly-Irving, M., Karisola, P., Kivimaki, M., Krogh, V., Laine, J., Lang, T., Layte, R., Lepage, B., Mackenbach, J., Marmot, M., de Mestral, C., McCrory, C., Milne, R., Muennig, P., Nusselder, W., Panico, S., Petrovic, D., Polidoro, S., Preisig, M., Raitakari, O., Ribeiro, A.I., Ricceri, F., Reinhard, E., Robinson, O., Valverde, J.R., Sacerdote, C., Satolli, R., Severi, G., Shipley, M.J., Stringhini, S., Tumino, R., Tieulent, J., Vaccarella, S., Vergnaud, A.C., Vineis, P., Vollenweider, P., Zins, M., Medical Research Council (MRC), and Commission of the European Communities
Subjects: LIFEPATH Consortium, Adult, Male, Mediation (statistics), medicine.medical_specialty, Socio-economic inequalities, Social Determinants of Health, Epidemiology, 030209 endocrinology & metabolism, 1117 Public Health and Health Services, health behaviours, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Cause of Death, all-cause mortality, causal inference, intervention, mediation, multiple mediators, Humans, Medicine, 030212 general & internal medicine, Mortality, ddc:613, Cause of death, business.industry, 0104 Statistics, Hazard ratio, Health Status Disparities, General Medicine, Middle Aged, Mortality/trends, Confidence interval, Editorial Commentary, Socioeconomic Factors, Female, Observational study, business, Body mass index, Demography, Cohort study
Abstract: Background Socio-economic inequalities in mortality are well established, yet the contribution of intermediate risk factors that may underlie these relationships remains unclear. We evaluated the role of multiple modifiable intermediate risk factors underlying socio-economic-associated mortality and quantified the potential impact of reducing early all-cause mortality by hypothetically altering socio-economic risk factors. Methods Data were from seven cohort studies participating in the LIFEPATH Consortium (total n = 179 090). Using both socio-economic position (SEP) (based on occupation) and education, we estimated the natural direct effect on all-cause mortality and the natural indirect effect via the joint mediating role of smoking, alcohol intake, dietary patterns, physical activity, body mass index, hypertension, diabetes and coronary artery disease. Hazard ratios (HRs) were estimated, using counterfactual natural effect models under different hypothetical actions of either lower or higher SEP or education. Results Lower SEP and education were associated with an increase in all-cause mortality within an average follow-up time of 17.5 years. Mortality was reduced via modelled hypothetical actions of increasing SEP or education. Through higher education, the HR was 0.85 [95% confidence interval (CI) 0.84, 0.86] for women and 0.71 (95% CI 0.70, 0.74) for men, compared with lower education. In addition, 34% and 38% of the effect was jointly mediated for women and men, respectively. The benefits from altering SEP were slightly more modest. Conclusions These observational findings support policies to reduce mortality both through improving socio-economic circumstances and increasing education, and by altering intermediaries, such as lifestyle behaviours and morbidities.
Published: 2019
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28. Anti-rod and ring antibodies in patients with chronic hepatitis C using direct-acting antivirals

Author: Norma Arteiro Filgueira, Edmundo Pessoa de Almeida Lopes, Silvana de Barros Barreto, Ana Beatriz da Silva Sacerdote, and Andrea Dória Batista
Subjects: Male, Simeprevir, medicine.medical_specialty, Pyrrolidines, Daclatasvir, Sustained Virologic Response, Sofosbuvir, Hepatitis C virus, Immunology, Hepacivirus, medicine.disease_cause, Antiviral Agents, Gastroenterology, chemistry.chemical_compound, Interferon, Internal medicine, Ribavirin, medicine, Humans, Fluorescent Antibody Technique, Indirect, Aged, biology, business.industry, Imidazoles, Autoantibody, Interferon-alpha, virus diseases, Valine, Hepatitis C, Chronic, Middle Aged, digestive system diseases, chemistry, Antibodies, Antinuclear, biology.protein, Drug Therapy, Combination, Female, Carbamates, Antibody, business, medicine.drug
Abstract: Anti-rods and rings (anti-RR) antibody induction is related to the combination of interferon and ribavirin in the treatment of hepatitis C virus (HCV) infection. If the main factor leading to this autoimmune reaction is the combination of these drugs, is not well known, but in vitro studies shows that ribavirin alone can induce rods and rings structures. New direct-acting antivirals (DAAs) permit HCV treatment without needing interferon but may be associated with ribavirin in the most difficult-to-treat patients. The aim of this study is to evaluate the occurrence of anti-RR in patients with chronic HCV infection, before and after 12 weeks of treatment with DAAs, with and without ribavirin. From Jun 2016 to Oct 2017, 52 HCV-infected patients were screened for anti-RR before and after DAA therapy, including sofosbuvir, daclatasvir, simeprevir, and ribavirin. Serum samples were analyzed using indirect immunofluorescence. The anti-RR was present in 11 (21%) of the 52 patients (51.9% male and mean age of 59.1 years) before using DAAs. All of them had been previously treated and previous exposed to interferon/ribavirin, with exposure time to ribavirin associated with the presence of anti-RR. After 12 weeks of DAA treatment, 3 patients (5.7%) developed the antibody in low titers, and two of them (66%) were interferon/ribavirin experienced. Only one of the 29 naïve patients (3.44%) developed anti-RR during the current treatment. Anti-RR was present in patients previously treated with interferon/ribavirin and can emerge after DAA treatment probably at a lower frequency than after interferon/ribavirin treatment.
Published: 2020
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29. Mediating role of lifestyle behaviors in the association between education and cancer: results from the European Prospective Investigation into Cancer and Nutrition

Author: Alessandra Macciotta, Alberto Catalano, Maria Teresa Giraudo, Elisabete Weiderpass, Pietro Ferrari, Heinz Freisling, Sandra M. Colorado-Yohar, Carmen Santiuste, Pilar Amiano, Alicia K. Heath, Heather A. Ward, Sofia Christakoudi, Paolo Vineis, Deependra Singh, Salvatore Vaccarella, Matthias B. Schulze, Anouk E. Hiensch, Evelyn M. Monninkhof, Verena Katzke, Rudolf Kaaks, Rosario Tumino, Fulvio Lazzarato, Lorenzo Milani, Antonio Agudo, Christina C. Dahm, Laura Baglietto, Vittorio Perduca, Gianluca Severi, Sara Grioni, Salvatore Panico, Eva Ardanaz, Kristin B. Borch, Faith O. Benebo, Tonje Braaten, Maria-Jose Sánchez, Claudia Giachino, Carlotta Sacerdote, and Fulvio Ricceri
Subjects: Male, Cohort Studies, Oncology, Epidemiology, Risk Factors, Incidence, Humans, Educational Status, Female, Breast Neoplasms, Prospective Studies, Life Style, Europe/epidemiology
Abstract: Background: Many studies have shown that socioeconomic position (SEP) is associated with the incidence of malignant tumors at different sites. This study aims to estimate the association between educational level (as proxy for SEP) and cancer incidence and to understand whether the observed associations might be partially explained by lifestyle behaviors. Methods: The analyses were performed on data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, globally and by sex. We used Cox proportional hazards models together with mediation analysis to disentangle the total effect (TE) of educational level [measured through the Relative Index of Inequality (RII)] on cancer incidence into pure direct (PDE) and total indirect (TIE) effect, unexplained and explained by mediators, respectively. PDE and TIE were then combined to compute the proportions mediated (PM). Results: After an average of 14 years of follow-up, 52,422 malignant tumors were ascertained. Low educated participants showed higher risk of developing stomach, lung, kidney (in women), and bladder (in men) cancers, and, conversely, lower risk of melanoma and breast cancer (in post-menopausal women), when compared with more educated participants. Mediation analyses showed that portions of the TE of RII on cancer could be explained by site-specific related lifestyle behaviors for stomach, lung, and breast (in women). Conclusions: Cancer incidence in Europe is determined at least in part by a socioeconomically stratified distribution of risk factors. Impact: These observational findings support policies to reduce cancer occurrence by altering mediators, such as lifestyle behaviors, particularly focusing on underprivileged strata of the population.
Published: 2022
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30. Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer

Author: Timothy H.T. Cheng, V. Wendy Setiawan, Jolanta Lissowska, Kamila Czene, Zhaoming Wang, Linda S. Cook, Shirley Hodgson, Mitul Shah, Matthias W. Beckmann, Douglas F. Easton, Annika Lindblom, Daniel D. Buchanan, Wei Zheng, Constance Turman, Gloria E. Sarto, Susan E. Hankinson, Chu Chen, Joe Dennis, Christine M. Friedenreich, Dylan M. Glubb, Peter Hillemanns, Tracy A. O'Mara, Camilla Krakstad, Yong-Bing Xiang, Arif B. Ekici, Maxine M. Chen, Marta Crous-Bous, Montserrat Garcia-Closas, David Van Den Berg, Amanda Black, Immaculata De Vivo, Roger L. Milne, Geoffrey Otton, Frédéric Amant, Timothy R. Rebbeck, Carlotta Sacerdote, Erling A. Hoivik, Xiao-Ou Shu, Melissa C. Southey, Paul L. Auer, Brooke L. Fridley, Thilo Dörk, Elizabeth G. Holliday, Fredrick R. Schumacher, Loreall Pooler, Daniela Annibali, Mia M. Gaudet, Maggie Gorman, Peter A. Fasching, Matthias Rübner, Hannah P. Yang, Graham G. Giles, Stefan P. Renner, Jirong Long, Ellen L. Goode, Katie A. Ashton, Claire Palles, Emma Tham, Diether Lambrechts, Xin Sheng, Rodney J. Scott, Angela M. Jones, Alexander Hein, Amanda B. Spurdle, Nicolas Wentzensen, David J. Hunter, Rami Nassir, Peter Kraft, Lynn Martin, Christopher A. Haiman, Alison M. Dunning, Stephen J. Chanock, Jone Trovik, Loic Le Marchand, Harvey A. Risch, Tony Proietto, Matthias Dürst, Sean C. Dowdy, Lucy Xia, Miriam Mints, Anthony M. Magliocco, Pik Fang Kho, Herbert Yu, Lingeng Lu, Mark McEvoy, Xiaolin Liang, Louise A. Brinton, Per Hall, Jonathan Tyrer, Ingo B. Runnebaum, Penelope M. Webb, John Attia, Ian Tomlinson, Deborah J. Thompson, Buchanan, Daniel D [0000-0003-2225-6675], Chen, Chu [0000-0003-2267-8050], De Vivo, Immaculata [0000-0002-7185-7402], Dörk, Thilo [0000-0002-9458-0282], Fasching, Peter A [0000-0003-4885-8471], Friedenreich, Christine M [0000-0002-4783-1966], Gaudet, Mia M [0000-0002-6429-4007], Goode, Ellen L [0000-0002-9094-8326], Lu, Lingeng [0000-0001-9871-0809], Sacerdote, Carlotta [0000-0002-8008-5096], Shu, Xiao-Ou [0000-0002-0711-8314], Wang, Zhaoming [0000-0001-7556-3869], Wentzensen, Nicolas [0000-0003-1251-0836], Xiang, Yong-Bing [0000-0002-3840-9915], Yu, Herbert [0000-0003-3950-4815], Spurdle, Amanda B [0000-0003-1337-7897], O'Mara, Tracy A [0000-0002-5436-3232], Apollo - University of Cambridge Repository, ARD - Amsterdam Reproduction and Development, Obstetrics and Gynaecology, and CCA - Imaging and biomarkers
Subjects: Oncology, Cancer Research, Colorectal cancer, Blood lipids, chemistry.chemical_compound, 0302 clinical medicine, HDL cholesterol, Medicine, triglycerides, METABOLIC SYNDROME, 2. Zero hunger, Mendelian Randomization Analysis, ASSOCIATION, 3. Good health, 030220 oncology & carcinogenesis, LDL cholesterol, SERUM-LIPIDS, Female, lipids (amino acids, peptides, and proteins), Life Sciences & Biomedicine, Risk, medicine.medical_specialty, endometrial cancer risk, Article, 03 medical and health sciences, INFLAMMATION, Internal medicine, Mendelian randomization, CAUSAL, Humans, Science & Technology, Cholesterol, business.industry, Endometrial cancer, Cholesterol, HDL, Case-control study, Cholesterol, LDL, medicine.disease, Endometrial Neoplasms, BODY-MASS INDEX, LIPOPROTEIN, chemistry, Case-Control Studies, RISK-FACTORS, Metabolic syndrome, business, Genome-Wide Association Study
Abstract: Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P
Published: 2021
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31. Dietary methyl-group donor intake and breast cancer risk in the european prospective investigation into cancer and nutrition (EPIC)

Author: Marc J. Gunter, Julie A. Schmidt, David C. Muller, Rosario Tumino, Inge Huybrechts, Matthias B. Schulze, Verena Katzke, Corinne Casagrande, Nikos Papadimitriou, Pietro Ferrari, María José Sánchez, Lode Godderis, Paolo Chiodini, Antonio Agudo, Anne Tjønneland, María Dolores López, Elisabete Weiderpass, Carine Biessy, Heleen Van Puyvelde, Valeria Pala, Alicia K Heath, Geneviève Nicolas, Kim Overvad, Eva Ardanaz, Giovanna Masala, Koen Van Herck, Therese Karlsson, Dirk De Bacquer, Björn Gylling, Carlotta Sacerdote, Ulrika Ericson, Renée T. Fortner, Marije F. Bakker, Joanna L Clasen, Jytte Halkjær, Jonas Manjer, Van Puyvelde, H., Papadimitriou, N., Clasen, J., Muller, D., Biessy, C., Ferrari, P., Halkjaer, J., Overvad, K., Tjonneland, A., Fortner, R. T., Katzke, V., Schulze, M. B., Chiodini, P., Masala, G., Pala, V., Sacerdote, C., Tumino, R., Bakker, M. F., Agudo, A., Ardanaz, E., Lopez, M. D. C., Sanchez, M. -J., Ericson, U., Gylling, B., Karlsson, T., Manjer, J., Schmidt, J. A., Nicolas, G., Casagrande, C., Weiderpass, E., Heath, A. K., Godderis, L., Van Herck, K., De Bacquer, D., Gunter, M. J., and Huybrechts, I.
Subjects: 0301 basic medicine, Folate, Physiology, ALCOHOL, EPIC, BETAINE, Choline, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Methionine, Risk Factors, Medicine and Health Sciences, Medicine, TX341-641, Prospective Studies, ONE-CARBON METABOLISM, DNA METHYLATION, Nutrition and Dietetics, ASSOCIATION, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Näringslära, Europe, Hormone receptor, FOLATE INTAKE, 030220 oncology & carcinogenesis, Cohort, Alcohol intake, Female, Life Sciences & Biomedicine, Breast Neoplasm, Human, Adult, DATABASE, Breast Neoplasms, folate, Methylation, Article, 03 medical and health sciences, breast cancer, Folic Acid, choline, Humans, Aged, methionine, Postmenopausal women, Science & Technology, Nutrition & Dietetics, business.industry, Nutrition. Foods and food supply, medicine.disease, Diet, Betaine, Prospective Studie, 030104 developmental biology, Nutrition Assessment, chemistry, B-VITAMINS, 1111 Nutrition and Dietetics, business, 0908 Food Sciences, Food Science
Abstract: We thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution to, and ongoing support of, the EPIC Study. We thank Aude De Bruycker for her graphical support., (1) Background: Methyl-group donors (MGDs), including folate, choline, betaine, and methionine, may influence breast cancer (BC) risk through their role in one-carbon metabolism; (2) Methods: We studied the relationship between dietary intakes of MGDs and BC risk, adopting data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort; (3) Results: 318,686 pre- and postmenopausal women were followed between enrolment in 1992–2000 and December 2013–December 2015. Dietary MGD intakes were estimated at baseline through foodfrequency questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary intake of MGDs, measured both as a calculated score based on their sum and individually, and BC risk. Subgroup analyses were performed by hormone receptor status, menopausal status, and level of alcohol intake. During a mean follow-up time of 14.1 years, 13,320 women with malignant BC were identified. No associations were found between dietary intakes of the MGD score or individual MGDs and BC risk. However, a potential U-shaped relationship was observed between dietary folate intake and overall BC risk, suggesting an inverse association for intakes up to 350 µg/day compared to a reference intake of 205 µg/day. No statistically significant differences in the associations were observed by hormone receptor status, menopausal status, or level of alcohol intake; (4) Conclusions: There was no strong evidence for an association between MGDs involved in one-carbon metabolism and BC risk. However, a potential U-shaped trend was suggested for dietary folate intake and BC risk. Further research is needed to clarify this association., Research Foundation Flanders (FWO, 189019N), Research Foundation Flanders (FWO, V427019N), International Agency for Research on Cancer (IARC), Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, NIHR Imperial Biomedical Research Center (BRC), Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology—ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford), (United Kingdom)
Published: 2021
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32. Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Amanda J. Cross, Kristin Benjaminsen Borch, Renée T. Fortner, Vittorio Simeon, Paul Brennan, Guri Skeie, Elio Riboli, Rosario Tumino, Elisabete Weiderpass, Gianluca Severi, Carlotta Sacerdote, Kim Overvad, Manuela M. Bergmann, Isabel Drake, Sara Grioni, Panagiota Pagoni, Giovanna Masala, Pietro Ferrari, Heinz Freisling, Matthias B. Schulze, Maria Dolores Chirlaque, Pilar Amiano, Mattias Johansson, Ioanna Tzoulaki, Konstantinos K. Tsilidis, Timothy J. Key, J. Ramón Quirós, Eva Ardanaz, Antonio Agudo, Neil Murphy, Marie-Christine Boutron-Ruault, Christel Häggström, Sofia Christakoudi, Rudolf Kaaks, Merete Ellingjord-Dale, Sophia Harlid, Charlotta Rylander, Tanja Stocks, Anne Tjønneland, Fanny Artaud, Laure Dossus, Jytte Halkjær, Miguel Rodríguez-Barranco, Aurora Perez-Cornago, David C. Muller, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC National Research Council, NRC Medical Research Council, MRC: MC_UU_00011/6, MR/M012190/1 Cancer Research UK, CRUK: C570/A16491, C8221/A19170 World Cancer Research Fund, WCRF European Commission, EC Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Vetenskapsrådet, VR Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Rijksinstituut voor Volksgezondheid en Milieu, RIVM Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN NIHR Imperial Biomedical Research Centre, BRC Fondation Gustave Roussy, The authors thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC study. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Kr?ftens Bek?mpelse) (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid (Deutsche Krebshilfe), German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Federal Ministry of Education and Research (Bundesministerium f?r Bildung und Forschung, BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS-ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barcelona) (Spain), Swedish Cancer Society (Cancerfonden), Swedish Research Council (Vetenskapsr?det), County Councils of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (MR/M012190/1 to EPIC-Oxford) (United Kingdom). Panagiota Pagoni is funded by Medical Research Council (grant reference MC_UU_00011/6). Infrastructure support for the Department of Epidemiology and Biostatistics at Imperial College London (UK) was provided by the NIHR Imperial Biomedical Research Centre (BRC). The funders had no role in the design and conduct of the study, the collection, analysis and interpretation of the data, or the preparation, review and approval of the manuscript, or in the decision to submit the manuscript for publication., The authors thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC study. The coordination of EPIC is financially supported by the European Commission (DG‐SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Kræftens Bekæmpelse) (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid (Deutsche Krebshilfe), German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy and National Research Council (Italy), Health Research Fund (FIS‐ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barcelona) (Spain), Swedish Cancer Society (Cancerfonden), Swedish Research Council (Vetenskapsrådet), County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/M012190/1 to EPIC‐Oxford) (United Kingdom). Panagiota Pagoni is funded by Medical Research Council (grant reference MC_UU_00011/6). Infrastructure support for the Department of Epidemiology and Biostatistics at Imperial College London (UK) was provided by the NIHR Imperial Biomedical Research Centre (BRC). The funders had no role in the design and conduct of the study, the collection, analysis and interpretation of the data, or the preparation, review and approval of the manuscript, or in the decision to submit the manuscript for publication., Associazione Italiana per la Ricerca sul Cancro, Bundesministerium für Bildung und Forschung, Cancer Research UK, Grant/Award Numbers: C570/A16491, C8221/A19170, Cancerfonden, Catalan Institute of Oncology Barcelona, Centre International de Recherche sur le Cancer, County Council of Skåne Sweden, County Council of Västerbotten Sweden, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, Directorate‐General for Health and Consumers, Dutch Ministry of Public Health, Welfare and Sports (VWS), Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), Health Research Fund (FIS‐ISCIII) Spain, Institut Gustave‐Roussy, Institut National de la Santé et de la Recherche Médicale, Kræftens Bekæmpelse, Ligue Contre le Cancer, LK Research Funds, Medical Research Council, Grant/Award Numbers: MC_UU_00011/6, MR/M012190/1, Mutuelle Générale de l'Education Nationale, National Research Council Italy, Netherlands Cancer Registry, Regional Government of Andalucía, Regional Government of Asturias, Regional Government of Basque Country, Regional Government of Murcia, Regional Government of Navarra, Statistics Netherlands, Vetenskapsrådet, World Cancer Research Fund (WCRF), Institut Gustave Roussy, International Agency for Research on Cancer, European Commission (DG‐SANCO) Funding information, Christakoudi, S., Pagoni, P., Ferrari, P., Cross, A. J., Tzoulaki, I., Muller, D. C., Weiderpass, E., Freisling, H., Murphy, N., Dossus, L., Turzanski Fortner, R., Agudo, A., Overvad, K., Perez-Cornago, A., Key, T. J., Brennan, P., Johansson, M., Tjonneland, A., Halkjaer, J., Boutron-Ruault, M. -C., Artaud, F., Severi, G., Kaaks, R., Schulze, M. B., Bergmann, M. M., Masala, G., Grioni, S., Simeon, V., Tumino, R., Sacerdote, C., Skeie, G., Rylander, C., Borch, K. B., Quiros, J. R., Rodriguez-Barranco, M., Chirlaque, M. -D., Ardanaz, E., Amiano, P., Drake, I., Stocks, T., Haggstrom, C., Harlid, S., Ellingjord-Dale, M., Riboli, E., Tsilidis, K. K., and Cancer Research UK
Subjects: Male, Cancer Research, middle adulthood, Overweight, Body Mass Index, Cohort Studies, 0302 clinical medicine, Weight loss, Risk Factors, Neoplasms, Prospective Studies, Correlation of Data, 2. Zero hunger, Ovarian Neoplasms, Obstetrics, Hazard ratio, PROLIFERATION, WOMEN, weight gain, Middle Aged, Kidney Neoplasms, 3. Good health, European Prospective Investigation into Cancer and Nutrition, BMI change, Europe, Oncology, 030220 oncology & carcinogenesis, ddc:540, Female, SQUAMOUS-CELL CARCINOMA, medicine.symptom, Life Sciences & Biomedicine, EXPRESSION, medicine.medical_specialty, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, LEPTIN, FATNESS, medicine, Humans, cancer, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Obesity, Risk factor, Proportional Hazards Models, Cancer och onkologi, Science & Technology, business.industry, Weight change, Endometrial Neoplasms, BODY-MASS INDEX, ESTROGEN-RECEPTORS, Pancreatic Neoplasms, Nutrition Assessment, Cancer and Oncology, Institut für Ernährungswissenschaft, GAIN, weight loss, business, Weight gain, Body mass index
Abstract: International audience; Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.
Published: 2021
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33. Pre-diagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma

Author: Heinz Freisling, Susana Merino, Aurelio Barricarte, Augustin Scalbert, Domenico Palli, Eleni Peppa, Hanna Nyström, Klas Sjöberg, Magdalena Stepien, Antonia Trichopoulou, Aurora Perez-Cornago, Marina Lopez-Nogueroles, Gianluca Severi, Carlotta Sacerdote, Dragos Ciocan, Tilman Kühn, Elisabete Weiderpass, Cosmin Sebastian Voican, Manuela M. Bergmann, Gabriel Perlemuter, Eugene Jansen, Rudolf Kaaks, Michael F. Leitzmann, Julie A. Schmidt, Catherine Dong, Anna Karakatsani, María José Sánchez, Rosario Tumino, Bodil Ohlsson, H. Bas Bueno-de-Mesquita, Marc J. Gunter, Raul Zamora Ros, Guri Skeie, José Mª Huerta, Heiner Boeing, Agustín Lahoz, Vittorio Krogh, Pilar Amiano, Francesca Mancini, Anne Tjønneland, Marie-Christine Boutron-Ruault, Salvatore Panico, Mazda Jenab, Sofia Christakoudi, Vivian Viallon, Renée T. Fortner, Mårten Werner, Faculté de Médecine Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: 1000143, MR/M012190/1, Cancer Research UK, CRUK: 14136, C8221/A29017, World Cancer Research Fund, WCRF, University of Cambridge, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Deutsche Krebshilfe, Institut National Du Cancer, INCa: 2009‐139, 2014‐1‐RT‐02‐CIRC‐1, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, This work was supported in part by the French National Cancer Institute (L'Institut National du Cancer, INCa, grant numbers 2009‐139 and 2014‐1‐RT‐02‐CIRC‐1, PI: M. Jenab) and by internal funds of the IARC. The coordination of EPIC is financially supported by the International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam‐Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra and the Catalan Institute of Oncology—ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC‐Norfolk, C8221/A29017 to EPIC‐Oxford), Medical Research Council (1000143 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford) (United Kingdom). The funding sources had no influence on the design of the study, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the article for publication. Funding information, and We would like to acknowledge Dr Krasimira Aleksandrova for input on the present manuscript, along with the National Institute for Public Health and the Environment (Bilthoven, The Netherlands), the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands, Department of Public Health Aarhus University (Aarhus, Denmark), University of Cambridge (Cambridge, United Kingdom), for their contributions and ongoing support to the EPIC Study.
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, obesity, Carcinoma, Hepatocellular, medicine.drug_class, education, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, Bile Acids and Salts, Cohort Studies, chemistry.chemical_compound, Internal medicine, medicine, Biomarkers, Tumor, Choline, Humans, Prospective cohort study, Carcinogen, Aged, Cancer prevention, Bile acid, cancer prevention, business.industry, Confounding, Liver Neoplasms, bile acid metabolism, biomarkers, hepatocellular carcinoma, Middle Aged, medicine.disease, Obesity, Oncology, chemistry, Hepatocellular carcinoma, Case-Control Studies, Female, business
Abstract: This is the peer reviewed version of the following article: Stepien et.al (2021). Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma. International Journal of Cancer, which has been published in final form at https://doi.org/10.1002/ijc.33885. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. Bile acids (BAs) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/unconjugated) in prediagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling = 2.30, 95% confidence intervals [CI]: 1.76-3.00), and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increase in BA concentration is accompanied by a shift in BA profile toward higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction.
Published: 2021
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34. The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Author: Nita G. Forouhi, Kim Overvad, Ivonne Sluijs, Tammy Y.N. Tong, Christina C. Dahm, Kay-Tee Khaw, Thomas E. Gundersen, José María Huerta, Peter M. Nilsson, Miguel Rodríguez-Barranco, Nasser Laouali, Adam S. Butterworth, Giovanna Masala, Sara Grioni, Rosario Tumino, Anja Olsen, Stephen J. Sharp, Salvatore Panico, J. Ramón Quirós, Yvonne T. van der Schouw, Eleanor Wheeler, Rudolf Kaaks, Alicia K Heath, Eva Ardanaz, Felix R. Day, Eleni Sofianopoulou, Konstantinos K. Tsilidis, Luca A. Lotta, Nicholas J. Wareham, Douae El-Fatouhi, Claudia Langenberg, Heiner Boeing, Guy Fagherazzi, Paula Jakszyn, Olov Rolandsson, Rupal L. Shah, Mazda Jenab, Miren Dorronsoro, Ju-Sheng Zheng, Fumiaki Imamura, Isobel D. Stewart, Elio Riboli, Paul W. Franks, Louise Hansen, John Danesh, Carlotta Sacerdote, Jian'an Luan, Niki Dimou, Annemieke M.W. Spijkerman, Tilman Kühn, Zheng, Ju-Sheng [0000-0001-6560-4890], Sharp, Stephen J [0000-0003-2375-1440], Day, Felix R [0000-0003-3789-7651], Sluijs, Ivonne [0000-0001-7758-4911], Shah, Rupal L [0000-0001-8789-8869], van der Schouw, Yvonne T [0000-0002-4605-435X], Dahm, Christina C [0000-0003-0481-2893], Dimou, Niki [0000-0003-1678-9328], Franks, Paul W [0000-0002-0520-7604], Fagherazzi, Guy [0000-0001-5033-5966], Huerta, José María [0000-0002-9637-3869], Heath, Alicia K [0000-0001-6517-1300], Hansen, Louise [0000-0002-7109-8864], Jenab, Mazda [0000-0002-0573-1852], Kühn, Tilman [0000-0001-7702-317X], Laouali, Nasser [0000-0002-8532-456X], Masala, Giovanna [0000-0002-5758-9069], Olsen, Anja [0000-0003-4788-503X], Rodríguez-Barranco, Miguel [0000-0002-9972-9779], Sacerdote, Carlotta [0000-0002-8008-5096], Tong, Tammy YN [0000-0002-0284-8959], Tumino, Rosario [0000-0003-2666-414X], Tsilidis, Konstantinos K [0000-0002-8452-8472], Riboli, Elio [0000-0001-6795-6080], Langenberg, Claudia [0000-0002-5017-7344], Forouhi, Nita G [0000-0002-5041-248X], Wareham, Nicholas J [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Sharp, Stephen J. [0000-0003-2375-1440], Day, Felix R. [0000-0003-3789-7651], Shah, Rupal L. [0000-0001-8789-8869], van der Schouw, Yvonne T. [0000-0002-4605-435X], Dahm, Christina C. [0000-0003-0481-2893], Franks, Paul W. [0000-0002-0520-7604], Heath, Alicia K. [0000-0001-6517-1300], Tong, Tammy Y. N. [0000-0002-0284-8959], Tsilidis, Konstantinos K. [0000-0002-8452-8472], Forouhi, Nita G. [0000-0002-5041-248X], and Wareham, Nicholas J. [0000-0003-1422-2993]
Subjects: Male, Single Nucleotide Polymorphisms, Organic chemistry, Genome-wide association study, Type 2 diabetes, VARIANTS, 030204 cardiovascular system & hematology, Biochemistry, Endocrinology, Medical Conditions, Mathematical and Statistical Techniques, 0302 clinical medicine, DESIGN, Risk Factors, Medicine and Health Sciences, Metabolites, VITAMIN-D SUPPLEMENTATION, 030212 general & internal medicine, Prospective Studies, Vitamin D, 11 Medical and Health Sciences, RISK, Diabetis, Statistics, Diabetes, Genomics, Vitamins, General Medicine, Metaanalysis, Middle Aged, Type 2 Diabetes, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Physical sciences, Chemistry, OBESITY, Endokrinologi och diabetes, Medicine, LIFE-STYLE, Female, Life Sciences & Biomedicine, Research Article, Adult, medicine.medical_specialty, Endocrine Disorders, DATABASE, Vitamina D, European Continental Ancestry Group, Single-nucleotide polymorphism, Endocrinology and Diabetes, Research and Analysis Methods, Lower risk, White People, Chemical compounds, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, Internal medicine, Organic compounds, Diabetes Mellitus, Genome-Wide Association Studies, medicine, Vitamin D and neurology, Genetics, Humans, Statistical Methods, Science & Technology, business.industry, Biology and Life Sciences, Computational Biology, Human Genetics, Odds ratio, Mendelian Randomization Analysis, Genome Analysis, medicine.disease, Metabolism, Diabetes Mellitus, Type 2, Genetic Loci, Metabolic Disorders, Relative risk, Dietary Supplements, GENETIC-DETERMINANTS, business, Mathematics, Genètica, Genome-Wide Association Study
Abstract: Background Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. Methods and findings We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]–InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1–standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. Conclusions Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D., Using both observational and genetic analyses, Ju-Sheng Zheng and colleagues investigate the relationship between vitamin D metabolites and type 2 diabetes among European individuals., Author summary Why was this study done? There is ongoing uncertainty on whether the body’s vitamin D status indicated by blood 25-hydroxyvitamin D (25(OH)D) is relevant to the prevention of type 2 diabetes. There are conflicting findings from observational studies and a limited number of randomised controlled trials. Prior research did not distinguish between different metabolites of total 25(OH)D, including 25(OH)D3 and C3-epi-25(OH)D3, an isomer of 25(OH)D3. It is not clear whether the associations of 25(OH)D metabolites with type 2 diabetes are causal, with conflicting findings from prior Mendelian randomisation studies of total 25(OH)D and no previous Mendelian randomisation studies appraising 25(OH)D metabolites. What did the researchers do and find? The current research compared observational estimates of the association between 25(OH)D metabolites and incident type 2 diabetes with Mendelian randomisation estimates based on genetic instruments. Using multiple data sources, we performed genome-wide association studies among 120,618 individuals for total 25(OH)D, and among 40,562 individuals for the other vitamin D metabolites. Among participants of European descent, 10 genetic loci were identified for total 25(OH)D, 7 loci for 25(OH)D3 and 3 loci for C3-epi-25(OH)D3. In meta-analysis of observational studies, we found that each 1–standard deviation higher level of total 25(OH)D was associated with 20% lower risk of type 2 diabetes. The result was similar for 25(OH)D3, but for C3-epi-25(OH)D3, a positive association with type 2 diabetes was found. With up to 80,983 type 2 diabetes cases and 842,909 controls, we assessed the association of genetically predicted differences in total 25(OH)D and its metabolites with type 2 diabetes. Neither genetically predicted higher total 25(OH)D level nor genetically predicted higher levels of 25(OH)D metabolites were significantly associated with type 2 diabetes. What do these findings mean? There were conflicting findings for a link with type 2 diabetes for the observational analysis of biochemically measured 25(OH)D metabolites versus the genetically predicted levels of these metabolites. The null findings based on Mendelian randomisation analysis indicate that blood levels of 25(OH)D or its metabolites are not likely to be causal factors for the development of type 2 diabetes. The current findings together with other evidence from randomised controlled trials do not support the use of vitamin D supplementation for the prevention of type 2 diabetes.
Published: 2020
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35. Replacement of Red and Processed Meat With Other Food Sources of Protein and the Risk of Type 2 Diabetes in European Populations: The EPIC-InterAct Study

Author: Anja Olsen, Stina Ramne, Inge Huybrechts, Keren Papier, Elio Riboli, Guy Fagherazzi, Marcela Guevara, Bernard Srour, Matthias B. Schulze, Vittorio Simeon, Paul W. Franks, Antonio Agudo, Daniel B Ibsen, Alicia K Heath, Heinz Freisling, Tammy Y.N. Tong, Sara Grioni, Nita G. Forouhi, Kim Overvad, Pilar Amiano, Verena A. Katze, Elisabete Weiderpass, Giovanna Masala, Dagfinn Aune, Benedetta Bendinelli, Carmen Santiuste, Yvonne T. van der Schouw, Marinka Steur, Rosario Tumino, Nicholas J. Wareham, Aurelio Barricarte, Clemens Wittenbecher, Fumiaki Imamura, José Ramón Quirós, Stephen J. Sharp, Francesca Mancini, Annemieke M.W. Spijkerman, Anne Tjønneland, Nasser Laouali, Olov Rolandsson, María José Sánchez, Carlotta Sacerdote, Ulrika Ericson, Ibsen, Daniel B [0000-0002-7038-4770], Schulze, Matthias B [0000-0002-0830-5277], Franks, Paul W [0000-0002-0520-7604], Rolandsson, Olov [0000-0002-1341-6828], Forouhi, Nita G [0000-0002-5041-248X], Apollo - University of Cambridge Repository, Ibsen, D. B., Steur, M., Imamura, F., Overvad, K., Schulze, M. B., Bendinelli, B., Guevara, M., Agudo, A., Amiano, P., Aune, D., Barricarte, A., Ericson, U., Fagherazzi, G., Franks, P. W., Freisling, H., Quiros, J. R., Grioni, S., Heath, A. K., Huybrechts, I., Katze, V., Laouali, N., Mancini, F., Masala, G., Olsen, A., Papier, K., Ramne, S., Rolandsson, O., Sacerdote, C., Sanchez, M. -J., Santiuste, C., Simeon, V., Spijkerman, A. M. W., Srour, B., Tjonneland, A., Tong, T. Y. N., Tumino, R., van der Schouw, Y. T., Weiderpass, E., Wittenbecher, C., Sharp, S. J., Riboli, E., Forouhi, N. G., Wareham, N. J., World Cancer Research Fund International, and Commission of the European Communities
Subjects: Male, Endocrinology, Diabetes and Metabolism, Population impact, Type 2 diabetes, EPIC, MELLITUS, 0302 clinical medicine, Risk Factors, Processed meat, 030212 general & internal medicine, Food science, Prospective Studies, 11 Medical and Health Sciences, IRON, Hazard ratio, food and beverages, MEN, ASSOCIATION, Middle Aged, Yogurt, CANCER, Europe, Milk, %22">Fish , Female, FERRITIN, Life Sciences & Biomedicine, COUNTRIES, 030209 endocrinology & metabolism, Endocrinology & Metabolism, 03 medical and health sciences, Diabetes mellitus, Internal Medicine, medicine, Animals, Humans, VALIDITY, Epidemiology/Health Services Research, METAANALYSIS, Aged, Proportional Hazards Models, Advanced and Specialized Nursing, Science & Technology, business.industry, CONSUMPTION, medicine.disease, Diet, Red Meat, Diabetes Mellitus, Type 2, Seafood, Causal association, Self Report, business, Follow-Up Studies
Abstract: OBJECTIVE There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact. RESEARCH DESIGN AND METHODS The European Prospective Investigation into Cancer (EPIC)-InterAct case cohort included 11,741 individuals with type 2 diabetes and a subcohort of 15,450 participants in eight countries. We modeled the replacement of self-reported red and processed meat with poultry, fish, eggs, legumes, cheese, cereals, yogurt, milk, and nuts. Country-specific hazard ratios (HRs) for incident type 2 diabetes were estimated by Prentice-weighted Cox regression and pooled using random-effects meta-analysis. RESULTS There was a lower hazard for type 2 diabetes for the modeled replacement of red and processed meat (50 g/day) with cheese (HR 0.90, 95% CI 0.83–0.97) (30 g/day), yogurt (0.90, 0.86–0.95) (70 g/day), nuts (0.90, 0.84–0.96) (10 g/day), or cereals (0.92, 0.88–0.96) (30 g/day) but not for replacements with poultry, fish, eggs, legumes, or milk. If a causal association is assumed, replacing red and processed meat with cheese, yogurt, or nuts could prevent 8.8%, 8.3%, or 7.5%, respectively, of new cases of type 2 diabetes. CONCLUSIONS Replacement of red and processed meat with cheese, yogurt, nuts, or cereals was associated with a lower rate of type 2 diabetes. Substituting red and processed meat by other protein sources may contribute to the prevention of incident type 2 diabetes in European populations.
Published: 2020
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36. Characterization of Synovial Cytokine Patterns in Bucket-Handle and Posterior Horn Meniscal Tears

Author: Marta Gandolla, Massimo Gorla, Antonio Torsello, Alessandra Pedrocchi, Davide Maggioni, Silvia Franchi, Marco Turati, Marco Bigoni, Giovanni Zatti, Robert J. Omeljaniuk, Paola Sacerdote, Nicolò Zanchi, Laura Rizzi, Turati, M, Maggioni, D, Zanchi, N, Gandolla, M, Gorla, M, Sacerdote, P, Franchi, S, Rizzi, L, Pedrocchi, A, Omeljaniuk, R, Zatti, G, Torsello, A, and Bigoni, M
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Article Subject, medicine.medical_treatment, Immunology, Meniscal tears, Osteoarthritis, Knee Injuries, Positive correlation, Proinflammatory cytokine, Lesion, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Synovial Fluid, Pathology, medicine, RB1-214, Synovial fluid, Humans, Aged, 030222 orthopedics, business.industry, Tumor Necrosis Factor-alpha, Cartilage, Interleukin-8, 030229 sport sciences, Cell Biology, Middle Aged, medicine.disease, Interleukin-10, Tibial Meniscus Injuries, medicine.anatomical_structure, Cytokine, Endocrinology, Female, medicine.symptom, business, cytokine, sinovial fluid, Research Article
Abstract: The specific etiology of meniscal tears, including the mechanism of lesion, location, and orientation, is considered for its contribution to subsequent joint cytokine responsiveness, healing outcomes, and by extension, appropriate lesion-specific surgical remediation. Meniscal repair is desirable to reduce the probability of development of posttraumatic osteoarthritis (PTOA) which is strongly influenced by the coordinate generation of pro- and anti-inflammatory cytokines by the injured cartilage. We now present biochemical data on variation in cytokine levels arising from two particular meniscal tears: bucket-handle (BH) and posterior horn (PH) isolated meniscal tears. We selected these two groups due to the different clinical presentations. We measured the concentrations of TNF-α, IL-1β, IL-6, IL-8, and IL-10 in knee synovial fluid of 45 patients with isolated meniscal lesions (BH tear, n = 12 ; PH tear, n = 33 ). TNF-α levels were significantly ( p < 0.05 ) greater in the BH group compared with the PH group, whereas IL-1β levels were significantly greater ( p < 0.05 ) in the PH group compared with the BH group. Both BH and PH groups were consistent in presenting a positive correlation between concentrations of IL-6 and IL-1β. A fundamental difference in IL-10 responsiveness between the two groups was noted; specifically, levels of IL-10 were positively correlated with IL-6 in the BH group, whereas in the PH group, levels of IL-10 were positively correlated with IL-1β. Collectively, our data suggest a possible influence of the meniscal tear pattern to the articular cytokine responsiveness. This differential expression of inflammatory cytokines may influence the risk of developing PTOA in the long term.
Published: 2020
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37. Covid-19 and clinical-epidemiological research in Italy: proposal of a research agenda on priority topics by the Italian association of epidemiology

Author: Giovannino, Ciccone, Silvia, Deandrea, Antonio, Clavenna, Ursula, Kirchmayer, Vittorio, Simeon, Anna, Acampora, Nerina, Agabiti, Laura, Angelici, Roita, Banzi, Ennio, Cadum, Anna, Castiglione, Paolo, Chiodini, Cinzia, Colombo, Eliana, Ferroni, Enrica, Migliore, Lorenza, Nisticò, Eva, Pagano, Anna Maria, Sabelli, Carlotta, Sacerdote, Caterina, Silvestri, Salvatore, Soldati, Saverio, Stranges, Marcello, Tirani, Marina, Davoli, Claudia, Galassi, Francesco, Forastiere, Ciccone, G., Deandrea, S., Clavenna, A., Kirchmayer, U., Simeon, V., Acampora, A., Agabiti, N., Angelici, L., Banzi, R., Cadum, E., Castiglione, A., Chiodini, P., Colombo, C., Ferroni, E., Migliore, E., Nistico, L., Pagano, E., Sabelli, A. M., Sacerdote, C., Silvestri, C., Soldati, S., Stranges, S., Tirani, M., Davoli, M., Galassi, C., and Forastiere, F.
Subjects: Adult, Male, Societies, Scientific, Epidemiology, Prognosi, epidemiologic methods, Coronavirus infections, pandemics, epidemiologic method, Pregnancy, Coronavirus infection, Humans, prevention and control, Pregnancy Complications, Infectious, Child, Pandemics, Aged, health services research evidence-based emergency medicine, Pandemic, SARS-CoV-2, Research, COVID-19, Middle Aged, Prognosis, COVID-19 Drug Treatment, Italy, Epidemiologic Research Design, Therapeutic Equipoise, Pregnancy Complications, Infectiou, Female, Human
Abstract: BACKGROUND: the Covid-19 pandemic has provoked a huge of clinical and epidemiological research initiatives, especially in the most involved countries. However, this very large effort was characterized by several methodological weaknesses, both in the field of discovering effective treatments (with too many small and uncontrolled trials) and in the field of identifying preventable risks and prognostic factors (with too few large, representative and well-designed cohorts orcase-control studies). OBJECTIVES: in response to the fragmented and uncoordinatedresearch production on Covid-19, the italian Association of Epidemiology (AIE) stimulated the formation of a working group (WG) with the aims of identifying the most important gaps in knowledge and to propose a structured research agenda of clinical and epidemiological studies considered at high priority on Covid-19, including recommendations on the preferable methodology. METHODS: the WG was composed by 25 subjects, mainly epidemiologists, statisticians, and other experts in specific fields, who have voluntarily agreed to the proposal. The agreement on a list of main research questions and on the structure of the specific documents to be produced were defined through few meetings and cycles of document exchanges. RESULTS: twelve main research questions on Covid-19 were identified, covering aetiology, prognosis,interventions, follow-up and impact on general and specific populations (children, pregnant women). For each of them, a two-page form was developed, structured in: background, main topics, methods (with recommendations on preferred study design and warnings for bias prevention) and an essential bibliography. CONCLUSIONS: this research agenda represents an initial contribution to direct clinical and epidemiological research efforts on high priority topics with a focus on methodological aspects. Further development and refinements of this agenda by Public Health Authorities are encouraged.
Published: 2020

38. Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: a Prospective Study and Meta-Analysis

Author: Matthias B. Schulze, Ruth C. Travis, Rosario Tumino, Rudolf Kaaks, Agnès Fournier, Niki Dimou, Pekka Keski-Rahkonen, Amanda J. Cross, Salvatore Panico, Marina Kvaskoff, Renée T. Fortner, María José Sánchez, Gianluca Severi, Dagfinn Aune, Carlotta Sacerdote, Marc J. Gunter, Konstantinos K. Tsilidis, Bas Bueno-de-Mesquita, Inger T. Gram, Eva Ardanaz, Sandra Colorado-Yohar, Marit Waaseth, Audrey Gicquiau, Vittorio Krogh, Paula Jakszyn, Sabina Rinaldi, Nagisa Mori, Justin Harbs, Neil Murphy, Sophia Harlid, Giovanna Masala, Eleanor L. Watts, and Bethany Van Guelpen
Subjects: Cancer Research, Colorectal cancer, Physiology, chemistry.chemical_compound, Sex hormone-binding globulin, Sex Hormone-Binding Globulin, Odds Ratio, Testosterone, Prospective Studies, Prospective cohort study, Gonadal Steroid Hormones, Progesterone, biology, Estradiol, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Dehydroepiandrosterone Sulfate, Middle Aged, Europe, Postmenopause, Oncology, Colonic Neoplasms, Female, Menopause, AcademicSubjects/MED00010, Menopausa, Estrone, Dehydroepiandrosterone, Article, Càncer colorectal, medicine, Confidence Intervals, Humans, Androstenedione, Cancer och onkologi, business.industry, Rectal Neoplasms, Estrogens, Odds ratio, medicine.disease, Logistic Models, chemistry, Cancer and Oncology, Case-Control Studies, biology.protein, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract: This work was supported by the French National Cancer Institute (INCa SHSESP17, grant No. 2017-127 to N. Murphy). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Ska degrees ne and V_asterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom)., Background: Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results. Methods: We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone–binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided. Results: In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment¼1.17 [95% confidence interval¼1.00 to 1.38]; odds ratioquartile4-quartile1¼1.33 [95% confidence interval¼0.89 to 1.97], Ptrend¼.20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the doseresponse meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk. Conclusion: Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women., French National Cancer Institute (INCa SHSESP17) 2017-127, World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe German Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition Potsdam Rehbruecke (DIfE) (Germany), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain) Junta de Andalucia Regional Government of Asturias (Spain) Regional Government of Basque Country (Spain) Regional Government of Murcia (Spain) Regional Government of Navarra (Spain) Catalan Institute of Oncology-ICO (Spain), Swedish Cancer Society Swedish Research Council County Council of Skane (Sweden) County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017 UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/M012190/1
Published: 2021

39. Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

Author: Angela M Wood, Stephen Kaptoge, Adam S Butterworth, Peter Willeit, Samantha Warnakula, Thomas Bolton, Ellie Paige, Dirk S Paul, Michael Sweeting, Stephen Burgess, Steven Bell, William Astle, David Stevens, Albert Koulman, Randi M Selmer, W M Monique Verschuren, Shinichi Sato, Inger Njølstad, Mark Woodward, Veikko Salomaa, Børge G Nordestgaard, Bu B Yeap, Astrid Fletcher, Olle Melander, Lewis H Kuller, Beverley Balkau, Michael Marmot, Wolfgang Koenig, Edoardo Casiglia, Cyrus Cooper, Volker Arndt, Oscar H Franco, Patrik Wennberg, John Gallacher, Agustín Gómez de la Cámara, Henry Völzke, Christina C Dahm, Caroline E Dale, Manuela M Bergmann, Carlos J Crespo, Yvonne T van der Schouw, Rudolf Kaaks, Leon A Simons, Pagona Lagiou, Josje D Schoufour, Jolanda M A Boer, Timothy J Key, Beatriz Rodriguez, Conchi Moreno-Iribas, Karina W Davidson, James O Taylor, Carlotta Sacerdote, Robert B Wallace, J Ramon Quiros, Rosario Tumino, Dan G Blazer, Allan Linneberg, Makoto Daimon, Salvatore Panico, Barbara Howard, Guri Skeie, Timo Strandberg, Elisabete Weiderpass, Paul J Nietert, Bruce M Psaty, Daan Kromhout, Elena Salamanca-Fernandez, Stefan Kiechl, Harlan M Krumholz, Sara Grioni, Domenico Palli, José M Huerta, Jackie Price, Johan Sundström, Larraitz Arriola, Hisatomi Arima, Ruth C Travis, Demosthenes B Panagiotakos, Anna Karakatsani, Antonia Trichopoulou, Tilman Kühn, Diederick E Grobbee, Elizabeth Barrett-Connor, Natasja van Schoor, Heiner Boeing, Kim Overvad, Jussi Kauhanen, Nick Wareham, Claudia Langenberg, Nita Forouhi, Maria Wennberg, Jean-Pierre Després, Mary Cushman, Jackie A Cooper, Carlos J Rodriguez, Masaru Sakurai, Jonathan E Shaw, Matthew Knuiman, Trudy Voortman, Christa Meisinger, Anne Tjønneland, Hermann Brenner, Luigi Palmieri, Jean Dallongeville, Eric J Brunner, Gerd Assmann, Maurizio Trevisan, Richard F Gillum, Ian Ford, Naveed Sattar, Mariana Lazo, Simon G Thompson, Pietro Ferrari, David A Leon, George Davey Smith, Richard Peto, Rod Jackson, Emily Banks, Emanuele Di Angelantonio, John Danesh, Adam Butterworth, Monique Verschuren, Salomaa Veikko, Astrid Flecther, Manuela Bergmann, Carlos Crespo, Jolanda M.A Boer, J. Ramon Quiros, Eric B Rimm, Dan G Blazer III, Jean-Pierre Dallongeville, Richard F Gillumn, Ian Ford Ford, Simon Thompson, Epidemiology, Wood, Angela M, Kaptoge, Stephen, Butterworth, Adam S, Willeit, Peter, Warnakula, Samantha, Bolton, Thoma, Paige, Ellie, Paul, Dirk S, Sweeting, Michael, Burgess, Stephen, Bell, Steven, Astle, William, Stevens, David, Koulman, Albert, Selmer, Randi M, Verschuren, W M Monique, Sato, Shinichi, Njølstad, Inger, Woodward, Mark, Salomaa, Veikko, Nordestgaard, Børge G, Yeap, Bu B, Fletcher, Astrid, Melander, Olle, Kuller, Lewis H, Balkau, Beverley, Marmot, Michael, Koenig, Wolfgang, Casiglia, Edoardo, Cooper, Cyru, Arndt, Volker, Franco, Oscar H, Wennberg, Patrik, Gallacher, John, de la Cámara, Agustín Gómez, Völzke, Henry, Dahm, Christina C, Dale, Caroline E, Bergmann, Manuela M, Crespo, Carlos J, van der Schouw, Yvonne T, Kaaks, Rudolf, Simons, Leon A, Lagiou, Pagona, Schoufour, Josje D, Boer, Jolanda M A, Key, Timothy J, Rodriguez, Beatriz, Moreno-Iribas, Conchi, Davidson, Karina W, Taylor, James O, Sacerdote, Carlotta, Wallace, Robert B, Quiros, J Ramon, Tumino, Rosario, Blazer, Dan G, Linneberg, Allan, Daimon, Makoto, Panico, Salvatore, Howard, Barbara, Skeie, Guri, Strandberg, Timo, Weiderpass, Elisabete, Nietert, Paul J, Psaty, Bruce M, Kromhout, Daan, Salamanca-Fernandez, Elena, Kiechl, Stefan, Krumholz, Harlan M, Grioni, Sara, Palli, Domenico, Huerta, José M, Price, Jackie, Sundström, Johan, Arriola, Larraitz, Arima, Hisatomi, Travis, Ruth C, Panagiotakos, Demosthenes B, Karakatsani, Anna, Trichopoulou, Antonia, Kühn, Tilman, Grobbee, Diederick E, Barrett-Connor, Elizabeth, van Schoor, Natasja, Boeing, Heiner, Overvad, Kim, Kauhanen, Jussi, Wareham, Nick, Langenberg, Claudia, Forouhi, Nita, Wennberg, Maria, Després, Jean-Pierre, Cushman, Mary, Cooper, Jackie A, Rodriguez, Carlos J, Sakurai, Masaru, Shaw, Jonathan E, Knuiman, Matthew, Voortman, Trudy, Meisinger, Christa, Tjønneland, Anne, Brenner, Hermann, Palmieri, Luigi, Dallongeville, Jean, Brunner, Eric J, Assmann, Gerd, Trevisan, Maurizio, Gillum, Richard F, Ford, Ian, Sattar, Naveed, Lazo, Mariana, Thompson, Simon G, Ferrari, Pietro, Leon, David A, Smith, George Davey, Peto, Richard, Jackson, Rod, Banks, Emily, Di Angelantonio, Emanuele, Danesh, John, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, HUS Internal Medicine and Rehabilitation, APH - Personalized Medicine, APH - Aging & Later Life, and Epidemiology and Data Science
Subjects: Male, FLOATING ABSOLUTE RISK, Alcohol abuse, BLOOD-PRESSURE, 030204 cardiovascular system & hematology, Alcohol Drinking/adverse effects, 0302 clinical medicine, Cardiovascular Disease, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, Prospective cohort study, Human Nutrition & Health, media_common, Medicine(all), VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Research Support, Non-U.S. Gov't, Humane Voeding & Gezondheid, Hazard ratio, Substance Abuse, Public Health, Global Health, Social Medicine and Epidemiology, ASSOCIATION, General Medicine, Middle Aged, ddc, 3. Good health, Substance abuse, Cardiovascular Diseases, CARDIOVASCULAR-DISEASE, MENDELIAN RANDOMIZATION, Female, Risk assessment, STROKE, Human, Alcohol Drinking, Lower risk, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Research Support, N.I.H., Extramural, US ADULTS, medicine, Journal Article, Life Science, Humans, media_common.cataloged_instance, CORONARY-HEART-DISEASE, ddc:610, Cardiovascular Diseases/etiology, European union, Beroendelära, METAANALYSIS, business.industry, MORTALITY, medicine.disease, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, 3121 General medicine, internal medicine and other clinical medicine, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Demography
Abstract: BACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.METHODS: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies.FINDINGS: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10–1·17), coronary disease excluding myocardial infarction (1·06, 1·00–1·11), heart failure (1·09, 1·03–1·15), fatal hypertensive disease (1·24, 1·15–1·33); and fatal aortic aneurysm (1·15, 1·03–1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91–0·97). In comparison to those who reported drinking >0–≤100 g per week, those who reported drinking >100–≤200 g per week, >200–≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1–2 years, or 4–5 years, respectively.INTERPRETATION: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.FUNDING: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.
Published: 2018
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40. Factors associated with serum ferritin levels and iron excess: results from the EPIC-EurGast study

Author: Lucía Rizzolo, Victoria Arija, Carlotta Sacerdote, Tilman Kühn, Antonio Agudo, Pilar Amiano, Nasser Laouali, Domenico Palli, Daniel A. Quintana Pacheco, Ramón Quirós, Carmen Santiuste, Emily Sonestedt, Isabel Drake, Elisabete Weiderpass, Lucía Iglesias-Vázquez, Rosario Tumino, Núria Aranda, P Jakszyn, Matthias B. Schulze, Amanda J. Cross, Elom K. Aglago, Eva Ardanaz, Maria Santucci de Magistris, and Daniel Redondo-Sánchez
Subjects: Male, Multivariate analysis, Iron Overload, ALCOHOL-CONSUMPTION, Iron, Medicine (miscellaneous), Physiology, Type 2 diabetes, Overweight, Systemic inflammation, Serum ferritin, DIETARY, medicine, Humans, HFE C282Y, BODY IRON, Hemochromatosis Protein, RISK, Science & Technology, Nutrition and Dietetics, Nutrition & Dietetics, DANISH MEN, business.industry, Iron status, Histocompatibility Antigens Class I, OVERLOAD, Cancer, Middle Aged, medicine.disease, CANCER, Obesity, PHYSICAL-ACTIVITY, Diabetes Mellitus, Type 2, Case-Control Studies, Ferritins, Red meat, 1111 Nutrition and Dietetics, Excess iron, Female, Hemochromatosis, medicine.symptom, business, EPIC, Life Sciences & Biomedicine
Abstract: Purpose Excess iron is involved in the development of non-communicable diseases such as cancer, type 2 diabetes and cardiovascular conditions. We aimed to describe the prevalence of excess iron and its determinants in healthy European adults. Methods Sociodemographic, lifestyle, iron status, dietary information, and HFE genotyping were obtained from controls from the nested case–control study EPIC-EurGast study. High sensitivity C-reactive protein (hsCRP) was measured to address possible systemic inflammation. Descriptive and multivariate analyses were used to assess iron status and its determinants. Results Out of the 828 participants (median age: 58.7 years), 43% were females. Median serum ferritin and prevalence of excess iron were 143.7 µg/L and 35.2% in males, respectively, and 77 µg/L and 20% in females, both increasing with latitude across Europe. Prevalence of HFE C282Y mutation was significantly higher in Northern and Central Europe (~ 11%) than in the South (5%). Overweight/obesity, age, and daily alcohol and heme iron intake were independent determinants for iron status, with sex differences even after excluding participants with hsCRP > 5 mg/L. Obese males showed a greater consumption of alcohol, total and red meat, and heme iron, compared with those normal weight. Conclusion Obesity, higher alcohol and heme iron consumption were the main risk factors for excess iron in males while only age was associated with iron overload in females. Weight control and promoting healthy lifestyle may help prevent iron overload, especially in obese people. Further research is needed to clarify determinants of excess iron in the healthy adult population, helping to reduce the associated comorbidities.
Published: 2021

41. Autoimmunity plays a role in the onset of diabetes after 40 years of age

Author: Vittorio Krogh, Rudolf Kaaks, Yvonne T. van der Schouw, Gianluca Severi, Eva Ardanaz, Marc J. Gunter, Tilman Kühn, Nicholas J. Wareham, Timothy J. Key, Francesca Mancini, Carlotta Sacerdote, María José Sánchez, Heiner Boeing, Annemieke M.W. Spijkerman, Peter M. Nilsson, Guy Fagherazzi, Miren Dorronsoro, María Dolores Chirlaque, Kay-Tee Khaw, Olov Rolandsson, Stephen J. Sharp, Salvatore Panico, Domenico Palli, Nita G. Forouhi, Christiane S. Hampe, Claudia Langenberg, Kim Overvad, Rosario Tumino, Elio Riboli, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), LSHM_CT_2006_037197 N∫ 6236 National Institutes of Health, NIH: DK26190 Compagnia di San Paolo Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Medical Research Council, MRC: MC_UU_12015/1, MC_UU_12015/5, MR/N003284/1 Cancer Research UK, CRUK World Cancer Research Fund, WCRF Bundesministerium für Bildung und Forschung, BMBF Västerbotten Läns Landsting Ministerie van Volksgezondheid, Welzijn en Sport, VWS Agentschap NL: IGE05012 Vetenskapsrådet, VR Umeå Universitet Bundesministerium für Forschung und Technologie, BMFT Deutsche Krebshilfe Bundesministerium fÃ¼r Bildung und Frauen, BMBF Stichting Diabetes Onderzoek Nederland NIHR Imperial Biomedical Research Centre, BRC NIHR Cambridge Biomedical Research Centre: IS-BRC-1215-20014, O. Rolandsson: The Västerboten County Council, M. Dorronsoro: We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as to the team of trained nurses who participated in the recruitment, R. Kaaks: German Cancer Aid, German Ministry of Research (BMBF), K. T. Khaw: Medical Research Council UK, Cancer Research UK, T. Kühn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), S. Panico: Compagnia di San Paolo, A. M. W. Spijkerman: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Statistics Netherlands (the Netherlands), EPIC Ragusa acknowledges for their participation blood donors of AVIS-Ragusa (local blood donors association), Y. T. van der Schouw: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Dutch ZON (Zorg Onderzoek Nederland), WCRF, Statistics Netherland, E. Riboli: Imperial College Biomedical Research Centre., Open access funding provided by Umea University. Funding for the InterAct project was provided by the EU FP6 Programme (grant number LSHM_CT_2006_037197). The autoantibody measurement was funded by Västerbotten County Council and Umeå University, Sweden (OR), the National Institutes of Health (DK26190) (CSH) and the Medical Research Council (MC_UU_12015/1) (NJW). OR: the Västerbotten County Council, Umeå University, MDC: Health Research Fund (FIS) of the Spanish Ministry of Health, Murcia Regional Government (N∫ 6236), EA: the Health Research Fund (FIS) of the Spanish Ministry of Health and Navarre Regional Government, RK: German Cancer Aid, the German Ministry of Research (BMBF), TJK: Cancer Research UK, KTK: the Medical Research Council UK, Cancer Research UK, PMN: the Swedish Research Council, KO: the Danish Cancer Society, SP: Compagnia di San Paolo, AMWS: the Dutch Ministry of Public Health, Welfare and Sports (VWS), the Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government, AMWS: LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), YTvdS: verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht, LK Research Funds, Dutch Prevention Funds, NGF: MRC core support (MC_UU_12015/5), NIHR Cambridge Biomedical Research Centre (IS-BRC-1215-20014). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Acknowledgements, We thank all EPIC participants and staff for their contribution to this study. We thank N. Kerrison (MRC Epidemiology Unit, Cambridge, UK) for managing the data and the laboratory team at the MRC Epidemiology Unit, Cambridge for managing the blood samples for the EPIC-InterAct project. We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as the team of trained nurses who participated in the recruitment. O. Rolandsson: The V?sterboten County Council, T. K?hn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), E. Riboli: Imperial College Biomedical Research Centre. Some of the data were presented as an abstract at the 54th EASD Annual Meeting in 2018., Rolandsson, Olov [0000-0002-1341-6828], and Apollo - University of Cambridge Repository
Subjects: Male, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Autoimmunity, Type 2 diabetes, medicine.disease_cause, LADA, Endocrinology, Autoantibody, 0302 clinical medicine, POPULATION, RISK, 0303 health sciences, Glutamate Decarboxylase, ANTIBODY POSITIVITY, GAD, Middle Aged, Phenotype, Genetic risk score, Pathophysiology, 3. Good health, Diabetes and Metabolism, Type 1 diabetes, Endokrinologi och diabetes, Female, Life Sciences & Biomedicine, Adult, 030209 endocrinology & metabolism, Endocrinology and Diabetes, Antibodies, Article, 1117 Public Health and Health Services, Endocrinology & Metabolism, 03 medical and health sciences, GLUTAMIC-ACID DECARBOXYLASE, Insulin resistance, Diabetes mellitus, Internal Medicine, medicine, Humans, TYPE-1, Aged, 030304 developmental biology, Science & Technology, business.industry, RECOGNITION, 1103 Clinical Sciences, ADULTS, medicine.disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Incident diabetes, Case-Control Studies, Immunology, 1114 Paediatrics and Reproductive Medicine, AUTOANTIBODIES, indident diabetes, business
Abstract: Aims/hypothesis Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. Methods GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. Results GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. Conclusions/interpretation Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.
Published: 2019
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42. Healthy lifestyle and the risk of pancreatic cancer in the EPIC study

Author: Paul Brennan, Salvatore Panico, Rosario Tumino, Isabel Drake, Kristin Benjaminsen Borch, Giovana Masala, Christina C. Dahm, Manuela M. Bergmann, Kim Overvad, Elisabete Weiderpass, Rudolf Kaaks, María José Sánchez, Sara Regnér, Anja Olsen, Elio Riboli, H. Bas Bueno-de-Mesquita, María Dolores López, Carlotta Sacerdote, Vinciane Rebours, Francesca Mancini, Marc J. Gunter, Eva Ardanaz, Antonia Trichopoulou, Vivian Viallon, Eric J. Duell, Anne M. May, Ruth C. Travis, Flavie Perrier, Anne Tjønneland, Heinz Freisling, José Ramón Quirós, Pilar Amiano Exezarreta, Verena Katzke, Valeria Pala, Eleni Peppa, Anna Karakatsani, Dagfinn Aune, Carla H. van Gils, Mazda Jenab, Fiona McKenzie, Heiner Boeing, Marie-Christine Boutron-Ruault, Sabine Naudin, Malin Sund, Dana Hashim, Nicholas J. Wareham, Charlotta Rylander, Pietro Ferrari, Naudin, Sabine [0000-0003-1049-6225], and Apollo - University of Cambridge Repository
Subjects: Male, Epidemiology, 030204 cardiovascular system & hematology, EPIC, Cohort Studies, 0302 clinical medicine, Risk Factors, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Pancreas cancer, Incidence, Incidence (epidemiology), Smoking, Obesity, Abdominal, Female, Epic study, Cohort study, Estils de vida, medicine.medical_specialty, Alcohol Drinking, Lifestyles, Nutritional Status, Estil de vida, Article, 1117 Public Health and Health Services, 03 medical and health sciences, Population attributable fraction, Pancreatic cancer, Humans, Healthy Lifestyle, Obesity, Prospective study, Nutrició, Exercise, Càncer de pàncrees, Nutrition, Proportional Hazards Models, Waist-Hip Ratio, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, business.industry, Healthy Lifestyle Index, Public health, Lifestyle, medicine.disease, Pancreatic Neoplasms, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Family medicine, business
Abstract: This is a post-peer-review, pre-copyedit version of an article published in the European Journal of Epidemiology. The final authenticated version is available online at: https://doi.org/10.1007/s10654-019-00559-6. Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants’ shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e−09) and 0.77 (0.72, 0.82; ptrend = 1.7e−15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e−04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.
Published: 2019
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43. Multi-cohort study identifies social determinants of systemic inflammation over the life course

Author: Berger, Eloïse, Castagné, Raphaële, Chadeau-Hyam, Marc, Bochud, Murielle, d’Errico, Angelo, Gandini, Martina, Karimi, Maryam, Kivimäki, Mika, Krogh, Vittorio, Marmot, Michael, Panico, Salvatore, Preisig, Martin, Ricceri, Fulvio, Sacerdote, Carlotta, Steptoe, Andrew, Stringhini, Silvia, Tumino, Rosario, Vineis, Paolo, Delpierre, Cyrille, Kelly-Irving, Michelle, Commission of the European Communities, Department of Public Health, Clinicum, and Faculty of Medicine
Subjects: Male, Genetics and Molecular Biology (all), Science, Health Behavior, Body Mass Index, C-Reactive Protein/metabolism, Female, Humans, Inflammation/immunology, Inflammation/metabolism, Regression Analysis, Risk Factors, Socioeconomic Factors, Biochemistry, Article, Physics and Astronomy (all), MARKERS, ADULT RISK-FACTORS, MD Multidisciplinary, CORONARY-HEART-DISEASE, MIDLIFE FINDINGS, lcsh:Science, WEAR-AND-TEAR, ddc:613, ADVERSE CHILDHOOD EXPERIENCES, Inflammation, Chemistry (all), EDUCATION, C-Reactive Protein, Biochemistry, Genetics and Molecular Biology (all), OBESITY, COURSE SOCIOECONOMIC POSITION, lcsh:Q, 3111 Biomedicine, Inflammation/immunology/metabolism
Abstract: Chronic inflammation has been proposed as having a prominent role in the construction of social inequalities in health. Disentangling the effects of early life and adulthood social disadvantage on inflammation is key in elucidating biological mechanisms underlying socioeconomic disparities. Here we explore the relationship between socioeconomic position (SEP) across the life course and inflammation (as measured by CRP levels) in up to 23,008 participants from six European cohort studies from three countries conducted between 1958 and 2013. We find a consistent inverse association between SEP and CRP across cohorts, where participants with a less advantaged SEP have higher levels of inflammation. Educational attainment is most strongly related to inflammation, after adjusting for health behaviours, body mass index and later-in-life SEP. These findings suggest socioeconomic disadvantage in young adulthood is independently associated with later life inflammation calling for further studies of the pathways operating through educational processes., Here, the authors explore the relationship between socioeconomic position (SEP) across the life course and inflammation in a multi-cohort study and show that educational attainment is most strongly related to inflammation, suggesting that socioeconomic disadvantage in young adulthood is independently associated with later life inflammation.
Published: 2019
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44. No association between polymorphisms in CYP2E1, GSTM1, NAT1, NAT2 and the risk of gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition

Author: Salvatore Panico, Nadia García, H. B. Bueno-De-Mesquita, Kim Overvad, Hendriek C. Boshuizen, Timothy J. Key, M. E. Numans, Antonio Berenguer, Rosario Tumino, Khaw K-T., Gabriele Nagel, Carmen Navarro, Boutron-Ruault M-C., Domenico Palli, Elio Riboli, J. Linseisen, Anne Tjønneland, Aurelio Barricarte, A. Olsen, Eiliv Lund, Françoise Clavel-Chapelon, Calogero Saieva, Teresa Norat, G. Del Giudice, Sheila Bingham, Guillem Pera, Henrik Simán, Antonia Trichopoulou, Mazda Jenab, Carlos A. González, Hendrik Bläker, J. R. Quirós, Carlos Martinez, Antonio Agudo, Roger Stenling, P. H. M. Peeters, Carlotta Sacerdote, Pilar Amiano, Pamela Ferrari, Naomi E. Allen, Göran Berglund, Fátima Carneiro, Gabriel Capellá, Franco Berrino, Heiner Boeing, Núria Sala, and Göran Hallmans
Subjects: Male, Oncology, medicine.medical_specialty, Pathology, Genotype, Arylamine N-Acetyltransferase, Epidemiology, Adenocarcinoma, Biology, Glutathione transferase, Gastric adenocarcinoma, Stomach Neoplasms, Internal medicine, medicine, Humans, Stomach cancer, neoplasms, Glutathione Transferase, Polymorphism, Genetic, integumentary system, Cytochrome P-450 CYP2E1, Middle Aged, medicine.disease, digestive system diseases, European Prospective Investigation into Cancer and Nutrition, Europe, Logistic Models, Case-Control Studies, Female, Stomach Adenocarcinoma
Abstract: No association between polymorphisms in CYP2E1, GSTM1, NAT1, NAT2 and the risk of gastric adenocarcinoma in the European prospective investigation into cancer and nutrition.
Published: 2021

45. Dietary intake of trans fatty acids and breast cancer risk in 9 European countries

Author: Sahar Yammine, Agnès Fournier, Ann H. Rosendahl, Carlotta Sacerdote, Renée T. Fortner, Marco Lukic, Elisabete Weiderpass, Karina Standahl Olsen, Dagfinn Aune, Sandra Colorado-Yohar, J. Ramón Quirós, Valeria Pala, Eva Ardanaz, María José Sánchez, Christina C. Dahm, Antonio Agudo, Anne Tjønneland, Franziska Jannasch, Giovanna Masala, Laure Dossus, Veronique Chajes, Alicia K Heath, Anja Olsen, Signe Borgquist, Maria Wennberg, Carine Biessy, Marc J. Gunter, Salvatore Panico, Inger T. Gram, Neil Murphy, Pilar Amiano, Julie A. Schmidt, Rosario Tumino, Michèle Matta, Corinne Casagrande, Matthias B. Schulze, Inge Huybrechts, Bernard Srour, Centre international de Recherche sur le Cancer (CIRC), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), The Arctic University of Norway [Tromsø, Norway] (UiT), Instituto de Investigación Sanitaria de Navarra [Pamplona, Spain] (IdiSNA), CIBER de Epidemiología y Salud Pública (CIBERESP), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), ibs.GRANADA Instituto de Investigación Biosanitaria [Granada, Spain], Universidad de Granada = University of Granada (UGR), Escuela Andaluza de Salud Pública [Granada, Spain] (EASP), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), German Institute of Human Nutrition Potsdam-Rehbruecke [Nuthetal, Germany] (GIHNP-R), Biodonostia Health Research Institute [Donostia-San Sebastian, Spain] (IIS Biodonostia), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), IMIB-Arrixaca [Murcia, Spain], Universidad de Murcia, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Public Health Directorate [Asturias, Spain] (PHD), Provincial Health Authority (ASP 7) [Ragusa, Italy], Université de Naples, Istituto per lo Studio, la Prevenzione e la rete Oncologica [Florence, Italy] (ISPRO), IRCCS Istituto Nazionale dei Tumori [Milano], City of Health and Science University Hospital [Turin, Italy], Danish Cancer Society Research Center [Copenhagen, Denmark] (DCSRC), University of Copenhagen = Københavns Universitet (UCPH), Aarhus University [Aarhus], Skane University Hospital [Lund], Umeå University, Imperial College London, Bjørknes University College [Oslo, Norvège], Oslo University Hospital [Oslo], University of Oxford, Malbec, Odile, The Arctic University of Norway (UiT), University of Granada [Granada], University of Copenhagen = Københavns Universitet (KU), and University of Oxford [Oxford]
Subjects: Industrial trans fatty acids, Conjugated linoleic acid, [SDV]Life Sciences [q-bio], Àcids grassos, Physiology, lcsh:Medicine, chemistry.chemical_compound, Eating, 0302 clinical medicine, Breast cancer, Risk Factors, Medicine, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, 2. Zero hunger, Nutrition and Dietetics, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Hazard ratio, General Medicine, Trans Fatty Acids, Elaidic acid, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Näringslära, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Dieta, Female, Research Article, Risk, Ruminant trans fatty acids, Breast Neoplasms, Càncer de mama, 03 medical and health sciences, General & Internal Medicine, Humans, Fatty acids, Proportional Hazards Models, Cancer och onkologi, business.industry, Proportional hazards model, lcsh:R, medicine.disease, Diet, chemistry, Cancer and Oncology, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Body mass index
Abstract: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada; PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPICNorfolk, MR/M012190/1 to EPIC-Oxford) (UK). We thank the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, and the National Institute for Public Health and the Environment (RIVM)-Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study., For information on how to submit an application for gaining access to EPIC data and/or biospecimens, please follow the instructions at http://epic.iarc.fr/ access/index.php., Informed consent was given by all study participants, and ethical approval for the entire EPIC cohort was obtained from the Institutional Review Board of the International Agency for Research on Cancer in Lyon, France, under protocol numbers SC/24/4 and SC/24/6, as well as from local ethics committees in the participating countries., The authors thank the EPIC participants and staff for their valuable contribution to this research and Bertrand Hemon (International Agency for Research on Cancer) for managing the data for the EPIC project., Background Trans fatty acids (TFAs) have been hypothesised to influence breast cancer risk. However, relatively few prospective studies have examined this relationship, and well-powered analyses according to hormone receptor-defined molecular subtypes, menopausal status, and body size have rarely been conducted. Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between dietary intakes of TFAs (industrial trans fatty acids [ITFAs] and ruminant trans fatty acids [RTFAs]) and breast cancer risk among 318,607 women. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for other breast cancer risk factors. Results After a median follow-up of 8.1 years, 13,241 breast cancer cases occurred. In the multivariable-adjusted model, higher total ITFA intake was associated with elevated breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). A similar positive association was found between intake of elaidic acid, the predominant ITFA, and breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). Intake of total RTFAs was also associated with higher breast cancer risk (HR for highest vs lowest quintile, 1.09, 95% CI 1.01-1.17; P trend = 0.015). For individual RTFAs, we found positive associations with breast cancer risk for dietary intakes of two strongly correlated fatty acids (Spearman correlation r = 0.77), conjugated linoleic acid (HR for highest vs lowest quintile, 1.11, 95% CI 1.03-1.20; P trend = 0.001) and palmitelaidic acid (HR for highest vs lowest quintile, 1.08, 95% CI 1.01-1.16; P trend = 0.028). Similar associations were found for total ITFAs and RTFAs with breast cancer risk according to menopausal status, body mass index, and breast cancer subtypes. Conclusions These results support the hypothesis that higher dietary intakes of ITFAs, in particular elaidic acid, are associated with elevated breast cancer risk. Due to the high correlation between conjugated linoleic acid and palmitelaidic acid, we were unable to disentangle the positive associations found for these fatty acids with breast cancer risk. Further mechanistic studies are needed to identify biological pathways that may underlie these associations., European Commission European Commission Joint Research Centre, International Agency for Research on Cancer, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, German Cancer Research Center (DKFZ) (Germany), Federal Ministry of Education & Research (BMBF), Deutsches Krebsforschungszentrum (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro (AIRC), Consiglio Nazionale delle Ricerche (CNR), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Netherlands Organization for Scientific Research (NWO), World Cancer Research Fund International (WCRF), Instituto de Salud Carlos III PI13/00061 PI13/01162, Junta de Andalucia, Catalan Institute of Oncology (Spain), Swedish Cancer Society Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C570/A16491 C8221/A19170, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/M012190/1, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, National Institute for Public Health and the Environment (RIVM)-Bilthoven, the Netherlands, Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), ERC-2009-AdG 232997
Published: 2021
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46. 'Journey of hope': a study on sexual gender-based violence reported by asylum-seeking women during their journey to Europe

Author: Bronsino, Martina, Castagneri, Chiara, Spinazzola, Matteo, Pepe, Roberto Raffaele, Sacerdote, Carlotta, and Ricceri, Fulvio
Subjects: asylum seeker, Europe, sexual gender-based violence, migrant women, regional hub, Refugees, Cross-Sectional Studies, Italy, Pregnancy, Humans, Female, Gender-Based Violence
Abstract: to describe sexual gender-based violence (SGBV) reported by asylum-seeking women during their journey from their country of origin to Italy, using data obtained from medical record of asylum seekers hosted between June 2016 and December 2017 at the "T. Fenoglio" Red Cross Reception Centre, one of the largest Italian regional hubs; to evaluate if, based on these data, it is possible to hypothesize an underreporting of SGBV from these women.cross-sectional study.2,484 asylum-seeking females hosted in the centre for initial-reception of Piedmont and Valle d'Aosta regions (Northern Italy) between June 2016 and December 2017.prevalence of SGBV.among the women arrived at the centre, 46 reported being victim of SGBV during their journey to Italy (prevalence: 1.85%; 95%CI 1.39-2.46), 37 of which with reliable and verified data supported by health certification documentation (prevalence: 1.49%; 95%CI 1.08-2.05). Women who suffered SGBV have a higher prevalence of diseases than their counterpart (more blood, digestive, neurological, psychological, genital diseases, and AIDS), are more frequently pregnant, and asked more frequently for a voluntary interruption of pregnancy.the low prevalence of SGBV identified suggests that underreporting and under-recognition of the phenomenon are possible. This highlights the need to offer a psychological support to all migrant women at their arrival in the Italian hubs, also when they do not report violence.
Published: 2021

47. Clinical characteristics and management of COVID-19 patients accessing the emergency department in a hospital in Northern Italy in March and April 2020

Author: Caramello, Valeria, Macciotta, Alessandra, De Salve, Alessandro Vincenzo, Gobbi, Valentina, Ruffino, Tommaso Maria, Mazzetti, Giulia, Ricagni, Lorenzo, Ling, Camilla, Arione, Roberto, Boccuzzi, Adriana, Costa, Giuseppe, Sacerdote, Carlotta, and Ricceri, Fulvio
Subjects: Male, Time Factors, emergency department, COVID-19, hospital management, in-hospital mortality, Comorbidity, Age Distribution, Hospitals, Urban, Humans, Hospital Mortality, Sex Distribution, Pandemics, Aged, Retrospective Studies, Aged, 80 and over, SARS-CoV-2, Disease Management, Middle Aged, Patient Discharge, COVID-19 Drug Treatment, Treatment Outcome, Italy, Mutation, Female, Symptom Assessment, Triage, Emergency Service, Hospital
Abstract: the emergency due to SARS-CoV-2 pandemic struck the national and regional health system that needed an effort to reorganise and increase resources to cope with a sudden, uncertain, and previously unknown situation. This study was conducted in the immediate aftermath of this difficult period.to describe clinical characteristics, short-term outcomes, and management of SARS-CoV-2 positive patients that accessed the emergency department (ED) of the San Luigi Gonzaga hospital of Orbassano (Turin district, Piedmont Region, Northern Italy) in March and April 2020. Furthermore, this study aimed at investigating if a difference in patients characteristics, clinical management, and outcomes was present during time.comparison of different periods in a clinical cohort.for each patient who accessed the ED and tested positive for SARS-CoV-2 swab, the ED medical record was collected and a descriptive analysis was performed on demographical characteristics, pre-existing comorbidities, parameters measured at triage, imaging exams results, lab tests results, separately for patients admitted at the ED in four different periods.discharge from ED, admission to hospital wards (low and high intensity of care), short term in-hospital mortality, hospital length of stay. The association between patients' characteristics and the main outcomes was measured using multivariable logistic models.age of patients increased significantly from March to April, together with female prevalence and associated comorbid conditions. A significant difference in symptoms at presentation was not observed nor it was in laboratory test results. Severity at triage and need of intensive care resources were higher in the first weeks, together with the typical clinical presentation with respiratory failure and imaging with signs of bilateral interstitial pneumonia. Accordingly, in-hospital mortality was higher in the first period. Nevertheless, nearly half of patients in the first period were discharged directly from ED showing mild COVID-19 cases. On the contrary, in April an increasing need of hospitalisation in low intensity of care beds was observed, whereas mild cases stopped to access the ED.the results of this study suggest that in few weeks of COVID-19 epidemic both management of the patients at the hospital level - and probably at territorial level resulting in a different population who accessed to the ED - and the clinical characteristics of the COVID-19 patients changed.
Published: 2021

48. Clinical and epidemiological characteristics associated with pneumonia at disease onset in patients admitted for COVID-19 to the Emergency Department of a large Hospital in Piedmont (North-Western Italy)

Author: Sacerdote, C., Castiglione, A., Pagano, E., Migliore, E., Pivetta, E., Auzzas, G. M., Brentisci, C., Brunetti, F., Defile, C., Gangemi, M., Giacometti, L., Gilardetti, M., Martins, V. H., Saccona, F., Stura, A., Turco, D., Balestro, C., Zozzoli, S., Fiandra, U., Roggero, S., Silvestre, C., Scozzari, G., Scarmozzino, A., and Ciccone, G.
Subjects: Adult, Diarrhea, Male, Time Factors, Vomiting, Pneumonia, Viral, Cohort study, COVID-19, Pneumonia, Aged, Aged, 80 and over, Comorbidity, Dyspnea, Emergency Service, Hospital, Female, Hospitals, University, Humans, Italy, Leukocyte Count, Middle Aged, Nervous System Diseases, Oxygen, Prospective Studies, Respiratory Rate, Retrospective Studies, Symptom Assessment, Pandemics, Hospital, 80 and over, Viral, Emergency Service, University, Hospitals
Abstract: to explore clinical and epidemiological characteristics associated with an imaging feature of COVID-19 pneumonia at disease onset, in order to identify factors that may be evaluable by general practitioners at patient's home, and which may lead to identify a more severe disease, needing hospitalization.this is a retrospective/prospective observational hospital cohort.the study population includes all patients consecutively admitted to the emergency department of Città della salute e della scienza University Hospital from 01.03 to 31.05.2020 with a confirmed diagnosis of SARS-CoV-2 infection.patients were classified in two groups according to the findings of X-ray imaging, lung ultrasound and chest computer tomography, as pneumonia or not pneumonia patients.in multivariable analysis, factors most strongly associated with emergency department admission with pneumonia were age, oxygen saturation90% (adj OR 4.16 ;95%CI 1.44-12.07), respiratory rate24 breaths/min (adj OR 6.50; 95%CI 2.36-17.87), fever ≥38° (adj OR 3.05; 95%CI 1.53-6.08) and the presence of gastroenteric symptoms (vomiting and diarrhea). A delay (7 days) between the appearance of the initial lung symptoms (cough and dyspnea) and the admission to the emergency department was also related to a higher probability of receiving a positive imaging report (OR 4.99; 95%CI 2,02-12,34).in order to reorganize the management of COVID-19 patients in Italy, in view of the risk of a second wave of epidemic or of local outbreaks, it would be desirable to relocate the triage, and possibly the patient's care, from hospital to home. In this scenario it is important to identify all symptoms and signs associated with COVID-19 pneumonia that would facilitate the decision-making process of GPs leading to patients hospitalization.
Published: 2021

49. A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author: Amanda J. Cross, Leila Lujan-Barroso, Matthias B. Schulze, Theron Johnson, Björn Gylling, Christina C. Dahm, José María Huerta, David C. Muller, Øivind Midttun, Giovanna Masala, Carlotta Sacerdote, Pilar Amiano, Joanna L Clasen, Mattias Johansson, Elio Riboli, Julie A. Schmidt, Ghislaine Scelo, Verena Katzke, Ulrika Ericson, Jin Young Park, Elisabete Weiderpass, Francesco Segrado, Marga C. Ocké, Arve Ulvik, Jonas Manjer, Pietro Ferrari, Ana Ching-López, Inge Huybrechts, Jytte Halkjær, Heleen Van Puyvelde, Alicia K Heath, Eva Ardanaz, Maria Santucci de Magistris, Anja Olsen, Ingegerd Johansson, Per Magne Ueland, and Cancer Research UK
Subjects: 0301 basic medicine, Oncology, Male, Vitamines, dietary biomarkers, Medicine (miscellaneous), HOMOCYSTEINE, Transsulfuration pathway, Status function, PLASMA PYRIDOXAL 5'-PHOSPHATE, vitamin B6, 09 Engineering, SERUM, AcademicSubjects/MED00160, chemistry.chemical_compound, 0302 clinical medicine, Vitamins, Minerals, and Phytochemicals, Neoplasms, DIETARY-INTAKE, Medicine and Health Sciences, Medicine, AMINO-ACIDS, Càncer, ONE-CARBON METABOLISM, 11 Medical and Health Sciences, Cancer, Nutrition and Dietetics, SOLUBLE VITAMINS, Factors de risc en les malalties, Biochemical markers, Vitamins, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Europe, Original Research Communications, MICROBIOLOGICAL ASSAY, 030220 oncology & carcinogenesis, Marcadors bioquímics, Epic study, Female, Vitamin B 6 Deficiency, Life Sciences & Biomedicine, kynurenine pathway, medicine.medical_specialty, Risk factors in diseases, Vitamin B 6/blood, BIOMARKERS, Nutritional Status, PLP, 03 medical and health sciences, AcademicSubjects/MED00060, Internal medicine, Humans, transsulfuration pathway, Pyridoxal, Aged, Cancer och onkologi, Science & Technology, 030109 nutrition & dietetics, Nutrition & Dietetics, business.industry, Metabolism, medicine.disease, Vitamin B 6, chemistry, Case-Control Studies, Cancer and Oncology, Linear Models, B-VITAMINS, Vitamin b6, business, Neoplasms/epidemiology
Abstract: BACKGROUND: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health. OBJECTIVES: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics. MEDTHODS: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP. RESULTS: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers. CONCLUSIONS: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors. ispartof: AMERICAN JOURNAL OF CLINICAL NUTRITION vol:114 issue:1 pages:338-347 ispartof: location:United States status: published
Published: 2021
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50. Urinary concentrations of (+)-catechin and (-)-epicatechin as biomarkers of dietary intake of flavan-3-ols in the european prospective investigation into cancer and nutrition (epic) study

Author: Matthias B. Schulze, David Achaintre, Enrique Almanza-Aguilera, Rosario Tumino, Joseph A. Rothwell, Theron Johnson, Verena Katzke, Gianluca Severi, Carlotta Sacerdote, Nasser Laouali, Domenico Palli, Maria Santucci de Magistris, Augustin Scalbert, Raul Zamora-Ros, Daniela Ceballos-Sánchez, Giuliana Gargano, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Universität Potsdam, Università degli studi di Napoli Federico II, Instituto de Salud Carlos III, ISCIII: PI18/00191, European Regional Development Fund, ERDF, Funding: This research was funded by the by the Institute of Health Carlos III through the grant PI18/00191 (co-funded by European Regional Development Fund. ERDF, a way to build Europe), and from the 553/C/2019 project, funded by La Marató de TV-3. The national EPIC cohorts are supported by the French National Cancer Institute (L’Institut National du Cancer, INCA Grant No. 2009-139), Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer, and Compagnia San Paolo (Italy). IDIBELL acknowledges support from the Generalitat de Catalunya through the CERCA Program. E.A.-A. and R.Z.-R. wish to thank the 'Sara Borrell' (CD20/00071) and the 'Miguel Servet' (CP CPII20/00009) programs from the Institute of Health Carlos III (co-funded by the European Social Fund (ESF)—ESF investing in your future).
Subjects: Male, Questionnaires, 030309 nutrition & dietetics, Urine, Catechin, chemistry.chemical_compound, Eating, Medicine, TX341-641, Food science, Prospective Studies, Epicatechin, 0303 health sciences, Nutrition and Dietetics, Biochemical markers, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Proanthocyanidin, Marcadors bioquímics, Intake, Female, Adult, Urinary system, Qüestionaris, Diet Surveys, Article, Statistics, Nonparametric, Flavan-3-ols, 03 medical and health sciences, Herbal tea, Flavan, Biflavonoids, Humans, Proanthocyanidins, 030304 developmental biology, Aged, Wine, Flavonoids, business.industry, Nutrition. Foods and food supply, Orina, Diet, Nutrition Assessment, chemistry, Food, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Aliments, business, EPIC, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers, Food Science
Abstract: This study examines the correlation of acute and habitual dietary intake of flavan-3-ol monomers, proanthocyanidins, theaflavins, and their main food sources with the urinary concentrations of (+)-catechin and (-)-epicatechin in the European Prospective Investigation into Cancer and Nutrition study (EPIC). Participants (N = 419, men and women) provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day. Acute and habitual dietary data were collected using a standardized 24-HDR software and a validated dietary questionnaire, respectively. Intake of flavan-3-ols was estimated using the Phenol-Explorer database. Concentrations of (+)-catechin and (-)-epicatechin in 24-h urine were analyzed using tandem mass spectrometry after enzymatic deconjugation. Simple and partial Spearman’s correlations showed that urinary concentrations of (+)-catechin, (-)-epicatechin and their sum were more strongly correlated with acute than with habitual intake of individual and total monomers (acute rpartial = 0.13–0.54, p &lt, 0.05, and habitual rpartial = 0.14–0.28, p &lt, 0.01), proanthocyanidins (acute rpartial = 0.24–0.49, p &lt, 0.001, and habitual rpartial = 0.10–0.15, p &lt, 0.05), theaflavins (acute rpartial = 0.22–0.31, p &lt, and habitual rpartial = 0.20–0.26, p &lt, 0.01), and total flavan-3-ols (acute rpartial = 0.40–0.48, p &lt, and habitual rpartial = 0.23–0.33, p &lt, 0.001). Similarly, urinary concentrations of flavan-3-ols were weakly correlated with both acute (rpartial = 0.12–0.30, p &lt, 0.05) and habitual intake (rpartial = 0.10–0.27, p &lt, 0.05) of apple and pear, stone fruits, berries, chocolate and chocolate products, cakes and pastries, tea, herbal tea, wine, red wine, and beer and cider. Moreover, all comparable correlations were stronger for urinary (-)-epicatechin than for (+)-catechin. In conclusion, our data support the use of urinary concentrations of (+)-catechin and (-)-epicatechin, especially as short-term nutritional biomarkers of dietary catechin, epicatechin and total flavan-3-ol monomers.
Published: 2021
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