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1. Genetic overlap between autoimmune diseases and non‐Hodgkin lymphoma subtypes

Author: Din, Lennox, Sheikh, Mohammad, Kosaraju, Nikitha, Smedby, Karin Ekstrom, Bernatsky, Sasha, Berndt, Sonja I, Skibola, Christine F, Nieters, Alexandra, Wang, Sophia, McKay, James D, Cocco, Pierluigi, Maynadié, Marc, Foretová, Lenka, Staines, Anthony, Mack, Thomas M, de Sanjosé, Silvia, Vyse, Timothy J, Padyukov, Leonid, Monnereau, Alain, Arslan, Alan A, Moore, Amy, Brooks‐Wilson, Angela R, Novak, Anne J, Glimelius, Bengt, Birmann, Brenda M, Link, Brian K, Stewart, Carolyn, Vajdic, Claire M, Haioun, Corinne, Magnani, Corrado, Conti, David V, Cox, David G, Casabonne, Delphine, Albanes, Demetrius, Kane, Eleanor, Roman, Eve, Muzi, Giacomo, Salles, Gilles, Giles, Graham G, Adami, Hans‐Olov, Ghesquières, Hervé, De Vivo, Immaculata, Clavel, Jacqueline, Cerhan, James R, Spinelli, John J, Hofmann, Jonathan, Vijai, Joseph, Curtin, Karen, Costenbader, Karen H, Onel, Kenan, Offit, Kenneth, Teras, Lauren R, Morton, Lindsay, Conde, Lucia, Miligi, Lucia, Melbye, Mads, Ennas, Maria Grazia, Liebow, Mark, Purdue, Mark P, Glenn, Martha, Southey, Melissa C, Din, Morris, Rothman, Nathaniel, Camp, Nicola J, Doo, Nicole Wong, Becker, Nikolaus, Pradhan, Nisha, Bracci, Paige M, Boffetta, Paolo, Vineis, Paolo, Brennan, Paul, Kraft, Peter, Lan, Qing, Severson, Richard K, Vermeulen, Roel CH, Milne, Roger L, Kaaks, Rudolph, Travis, Ruth C, Weinstein, Stephanie J, Chanock, Stephen J, Ansell, Stephen M, Slager, Susan L, Zheng, Tongzhang, Zhang, Yawei, Benavente, Yolanda, Taub, Zachary, Madireddy, Lohith, Gourraud, Pierre‐Antoine, Oksenberg, Jorge R, Cozen, Wendy, Hjalgrim, Henrik, and Khankhanian, Pouya
Subjects: Biological Sciences, Genetics, Lymphoma, Arthritis, Neurodegenerative, Brain Disorders, Autoimmune Disease, Cancer, Human Genome, Rare Diseases, Hematology, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Alleles, Autoimmune Diseases, Female, Genetic Predisposition to Disease, HLA Antigens, Humans, Lymphoma, Non-Hodgkin, Male, Middle Aged, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Factors, autoimmune disease, genome-wide association study, meta-analysis, non-Hodgkin lymphoma, Public Health and Health Services, Epidemiology
Abstract: Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
Published: 2019

2. Prediction of acute myeloid leukaemia risk in healthy individuals.

Author: Abelson, Sagi, Collord, Grace, Ng, Stanley WK, Weissbrod, Omer, Mendelson Cohen, Netta, Niemeyer, Elisabeth, Barda, Noam, Zuzarte, Philip C, Heisler, Lawrence, Sundaravadanam, Yogi, Luben, Robert, Hayat, Shabina, Wang, Ting Ting, Zhao, Zhen, Cirlan, Iulia, Pugh, Trevor J, Soave, David, Ng, Karen, Latimer, Calli, Hardy, Claire, Raine, Keiran, Jones, David, Hoult, Diana, Britten, Abigail, McPherson, John D, Johansson, Mattias, Mbabaali, Faridah, Eagles, Jenna, Miller, Jessica K, Pasternack, Danielle, Timms, Lee, Krzyzanowski, Paul, Awadalla, Philip, Costa, Rui, Segal, Eran, Bratman, Scott V, Beer, Philip, Behjati, Sam, Martincorena, Inigo, Wang, Jean CY, Bowles, Kristian M, Quirós, J Ramón, Karakatsani, Anna, La Vecchia, Carlo, Trichopoulou, Antonia, Salamanca-Fernández, Elena, Huerta, José M, Barricarte, Aurelio, Travis, Ruth C, Tumino, Rosario, Masala, Giovanna, Boeing, Heiner, Panico, Salvatore, Kaaks, Rudolf, Krämer, Alwin, Sieri, Sabina, Riboli, Elio, Vineis, Paolo, Foll, Matthieu, McKay, James, Polidoro, Silvia, Sala, Núria, Khaw, Kay-Tee, Vermeulen, Roel, Campbell, Peter J, Papaemmanuil, Elli, Minden, Mark D, Tanay, Amos, Balicer, Ran D, Wareham, Nicholas J, Gerstung, Moritz, Dick, John E, Brennan, Paul, Vassiliou, George S, and Shlush, Liran I
Subjects: Humans, Disease Progression, Genetic Predisposition to Disease, Prevalence, Risk Assessment, Age Factors, Mutagenesis, Mutation, Models, Genetic, Adult, Aged, Middle Aged, Health, Female, Male, Leukemia, Myeloid, Acute, Electronic Health Records, Models, Genetic, Leukemia, Myeloid, Acute, General Science & Technology
Abstract: The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure1. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion2,3. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)4-8. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.
Published: 2018

3. Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Author: Molina‐Montes, Esther, Sánchez, María‐José, Zamora‐Ros, Raul, Bueno‐de‐Mesquita, HB, Wark, Petra A, Obon‐Santacana, Mireia, Kühn, Tilman, Katzke, Verena, Travis, Ruth C, Ye, Weimin, Sund, Malin, Naccarati, Alessio, Mattiello, Amalia, Krogh, Vittorio, Martorana, Caterina, Masala, Giovanna, Amiano, Pilar, Huerta, José‐María, Barricarte, Aurelio, Quirós, José‐Ramón, Weiderpass, Elisabete, Åsli, Lene Angell, Skeie, Guri, Ericson, Ulrika, Sonestedt, Emily, Peeters, Petra H, Romieu, Isabelle, Scalbert, Augustin, Overvad, Kim, Clemens, Matthias, Boeing, Heiner, Trichopoulou, Antonia, Peppa, Eleni, Vidalis, Pavlos, Khaw, Kay‐Tee, Wareham, Nick, Olsen, Anja, Tjønneland, Anne, Boutroun‐Rualt, Marie‐Christine, Clavel‐Chapelon, Françoise, Cross, Amanda J, Lu, Yunxia, Riboli, Elio, and Duell, Eric J
Subjects: Biomedical and Clinical Sciences, Nutrition and Dietetics, Digestive Diseases, Nutrition, Pancreatic Cancer, Rare Diseases, Complementary and Integrative Health, Cancer, Prevention, Cohort Studies, Diet, Diet Records, Europe, Female, Flavonoids, Humans, Life Style, Lignans, Male, Middle Aged, Pancreatic Neoplasms, Proportional Hazards Models, Prospective Studies, cohort, diet, flavonoids, lignans, pancreatic cancer, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow-up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center-stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable-adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95-1.11 and 1.02; 95% CI: 0.89-1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91-1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.
Published: 2016

4. Comparison of abdominal adiposity and overall obesity in relation to risk of small intestinal cancer in a European Prospective Cohort

Author: Lu, Yunxia, Cross, Amanda J, Murphy, Neil, Freisling, Heinz, Travis, Ruth C, Ferrari, Pietro, Katzke, Verena A, Kaaks, Rudolf, Olsson, Åsa, Johansson, Ingegerd, Renström, Frida, Panico, Salvatore, Pala, Valeria, Palli, Domenico, Tumino, Rosario, Peeters, Petra H, Siersema, Peter D, Bueno-de-Mesquita, HB, Trichopoulou, Antonia, Klinaki, Eleni, Tsironis, Christos, Agudo, Antonio, Navarro, Carmen, Sánchez, María-José, Barricarte, Aurelio, Boutron-Ruault, Marie-Christine, Fagherazzi, Guy, Racine, Antoine, Weiderpass, Elisabete, Gunter, Marc J, and Riboli, Elio
Subjects: Biomedical and Clinical Sciences, Epidemiology, Public Health, Health Sciences, Nutrition and Dietetics, Obesity, Prevention, Nutrition, Cancer, Digestive Diseases, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Cardiovascular, Stroke, Adenocarcinoma, Adiposity, Adult, Aged, Body Height, Body Mass Index, Europe, Female, Humans, Intestinal Neoplasms, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Factors, Waist Circumference, Waist-Hip Ratio, White People, Abdominal obesity, Small intestine, Oncology and Carcinogenesis, Public Health and Health Services, Oncology and carcinogenesis
Abstract: BackgroundThe etiology of small intestinal cancer (SIC) is largely unknown, and there are very few epidemiological studies published to date. No studies have investigated abdominal adiposity in relation to SIC.MethodsWe investigated overall obesity and abdominal adiposity in relation to SIC in the European Prospective Investigation into Cancer and Nutrition (EPIC), a large prospective cohort of approximately half a million men and women from ten European countries. Overall obesity and abdominal obesity were assessed by body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Multivariate Cox proportional hazards regression modeling was performed to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Stratified analyses were conducted by sex, BMI, and smoking status.ResultsDuring an average of 13.9 years of follow-up, 131 incident cases of SIC (including 41 adenocarcinomas, 44 malignant carcinoid tumors, 15 sarcomas and 10 lymphomas, and 21 unknown histology) were identified. WC was positively associated with SIC in a crude model that also included BMI (HR per 5-cm increase = 1.20, 95 % CI 1.04, 1.39), but this association attenuated in the multivariable model (HR 1.18, 95 % CI 0.98, 1.42). However, the association between WC and SIC was strengthened when the analysis was restricted to adenocarcinoma of the small intestine (multivariable HR adjusted for BMI = 1.56, 95 % CI 1.11, 2.17). There were no other significant associations.ConclusionWC, rather than BMI, may be positively associated with adenocarcinomas but not carcinoid tumors of the small intestine.ImpactAbdominal obesity is a potential risk factor for adenocarcinoma in the small intestine.
Published: 2016

5. 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

6. Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci

Author: Kachuri, Linda, Amos, Christopher I, McKay, James D, Johansson, Mattias, Vineis, Paolo, Bueno-de-Mesquita, H Bas, Boutron-Ruault, Marie-Christine, Johansson, Mikael, Quirós, J Ramón, Sieri, Sabina, Travis, Ruth C, Weiderpass, Elisabete, Le Marchand, Loic, Henderson, Brian E, Wilkens, Lynne, Goodman, Gary E, Chen, Chu, Doherty, Jennifer A, Christiani, David C, Wei, Yongyue, Su, Li, Tworoger, Shelley, Zhang, Xuehong, Kraft, Peter, Zaridze, David, Field, John K, Marcus, Michael W, Davies, Michael PA, Hyde, Russell, Caporaso, Neil E, Landi, Maria Teresa, Severi, Gianluca, Giles, Graham G, Liu, Geoffrey, McLaughlin, John R, Li, Yafang, Xiao, Xiangjun, Fehringer, Gord, Zong, Xuchen, Denroche, Robert E, Zuzarte, Philip C, McPherson, John D, Brennan, Paul, and Hung, Rayjean J
Subjects: Lung, Human Genome, Genetics, Cancer, Prevention, Lung Cancer, 2.1 Biological and endogenous factors, Aetiology, Case-Control Studies, Chromosome Mapping, Chromosomes, Human, Pair 5, Female, Genetic Loci, Genetic Predisposition to Disease, Genotyping Techniques, Humans, Lung Neoplasms, Male, Middle Aged, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract: Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.
Published: 2016

7. Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort

Author: Duarte-Salles, Talita, Fedirko, Veronika, Stepien, Magdalena, Aleksandrova, Krasimira, Bamia, Christina, Lagiou, Pagona, Laursen, Anne Sofie Dam, Hansen, Louise, Overvad, Kim, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Fagherazzi, Guy, His, Mathilde, Boeing, Heiner, Katzke, Verena, Kühn, Tilman, Trichopoulou, Antonia, Valanou, Elissavet, Kritikou, Maria, Masala, Giovanna, Panico, Salvatore, Sieri, Sabina, Ricceri, Fulvio, Tumino, Rosario, Bueno-de-Mesquita, HB As, Peeters, Petra H, Hjartåker, Anette, Skeie, Guri, Weiderpass, Elisabete, Ardanaz, Eva, Bonet, Catalina, Chirlaque, Maria-Dolores, Dorronsoro, Miren, Quirós, J Ramón, Johansson, Ingegerd, Ohlsson, Bodil, Sjöberg, Klas, Wennberg, Maria, Khaw, Kay-Tee, Travis, Ruth C, Wareham, Nick, Ferrari, Pietro, Freisling, Heinz, Romieu, Isabelle, Cross, Amanda J, Gunter, Marc, Lu, Yunxia, and Jenab, Mazda
Subjects: Biomedical and Clinical Sciences, Nutrition and Dietetics, Hepatitis, Infectious Diseases, Hepatitis - B, Liver Cancer, Prevention, Liver Disease, Cancer, Chronic Liver Disease and Cirrhosis, Rare Diseases, Nutrition, Digestive Diseases, Clinical Research, Emerging Infectious Diseases, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Adult, Aged, Carcinoma, Hepatocellular, Case-Control Studies, Diet, Dietary Fats, Europe, Feeding Behavior, Female, Humans, Incidence, Life Style, Liver Neoplasms, Male, Middle Aged, Nutritional Status, Prospective Studies, Risk, Risk Factors, Surveys and Questionnaires, Young Adult, European populations, cohort study, dietary fats, hepatocellular carcinoma, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk.
Published: 2015

8. A Prospective Study of the Immune System Activation Biomarker Neopterin and Colorectal Cancer Risk

Author: Aleksandrova, Krasimira, Chuang, Shu-Chun, Boeing, Heiner, Zuo, Hui, Tell, Grethe S, Pischon, Tobias, Jenab, Mazda, Bueno-de-Mesquita, Bas, Vollset, Stein Emil, Midttun, Øivind, Ueland, Per Magne, Fedirko, Veronika, Johansson, Mattias, Weiderpass, Elisabete, Severi, Gianluca, Racine, Antoine, Boutron-Ruault, Marie-Christine, Kaaks, Rudolf, Kühn, Tilman, Tjønneland, Anne, Overvad, Kim, Quirós, J Ramón, Jakszyn, Paula, Sánchez, María-José, Dorronsoro, Miren, Chirlaque, Maria-Dolores, Ardanaz, Eva, Khaw, Kay-Tee, Wareham, Nicholas J, Travis, Ruth C, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Panico, Salvatore, May, Anne M, Palmqvist, Richard, Ljuslinder, Ingrid, Kong, So Yeon J, Freisling, Heinz, Gunter, Marc J, Lu, Yunxia, Cross, Amanda J, Riboli, Elio, and Vineis, Paolo
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Colo-Rectal Cancer, Cancer, Clinical Research, Digestive Diseases, Adult, Aged, Biomarkers, Tumor, Case-Control Studies, Chromatography, Liquid, Colonic Neoplasms, Colorectal Neoplasms, Europe, Female, Humans, Immunity, Cellular, Male, Middle Aged, Neopterin, Odds Ratio, Prospective Studies, Rectal Neoplasms, Sensitivity and Specificity, T-Lymphocytes, Helper-Inducer, Tandem Mass Spectrometry, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P difference = .87) and after excluding case patients diagnosed within the first four follow-up years. These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.
Published: 2015

9. Blood Metal Levels and Amyotrophic Lateral Sclerosis Risk: A Prospective Cohort

Author: Broberg, Karin E., Kippler, Maria J., Veldink, Jan Herman, Van Den Berg, Leonard H., Middleton, Lefkos T., Travis, Ruth C., Bergmann, Manuela M., Mancini, Francesca Romana, Katzke, Verena Andrea, Agudo, Antonio T., Gómez, Jesús Humberto, Rodríguez-Barranco, Miguel A., Trichopoulou, Antonia D., Vermeulen, Roel C.H., Peters, Susan, Broberg, Karin, Gallo, Valentina, Levi, Michael, Kippler, Maria, Vineis, Paolo, Veldink, Jan, Berg, Leonard, Middleton, Lefkos, Travis, Ruth, Bergmann, Manuela, Palli, Domenico, Grioni, Sara, Tumino, Rosario, Elbaz, Alexis, Vlaar, Tim, Mancini, Francesca, Kühn, Tilman, Katzke, Verena, Agudo, Antonio, Goñi, Fernando, Gómez, Jesús‐humberto, Rodríguez‐barranco, Miguel, Merino, Susana, Barricarte, Aurelio, Trichopoulou, Antonia, Jenab, Mazda, Weiderpass, Elisabete, Vermeulen, Roel, Santé publique France - French National Public Health Agency [Saint-Maurice, 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, Institut Gustave Roussy (IGR), 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), FOOD‐CT‐2005‐513943 Ministry of National Education and Religious Affairs Cancer Research UK, CRUK Wellcome Trust, WT German Cancer Research Center, DKFZ Department of Health, Australian Government Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS Instituto de Salud Carlos III, ISCIII: C03/09 Stichting Diabetes Onderzoek Nederland British Heart Foundation, BHF Norges Forskningsråd QLK4CT199900927 Stroke Association European Commission, EC Deutsche Krebshilfe World Cancer Research Fund, WCRF Kreftforeningen, NCS Medical Research Council, MRC, The EPIC study is funded by a number of grants, however, no funding source had any role in the preparation of this article. The EPIC study was funded by the Europe against Cancer program of the European Commission (SANCO), Italian Association for Research on Cancer, and Italian National Research Council. In addition, the authors thank the following for their financial support: the Environmental Cancer Risk, Nutrition, and Individual Susceptibility Network of Excellence, operating within the European Union Sixth Framework Program, Priority 5: Food Quality and Safety (FOOD‐CT‐2005‐513943), European Community Fifth Framework Program (grant QLK4CT199900927), ISCIII, Red de Centros RCESP (C03/09), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia, and Navarra, Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Greek Ministry of Health, Greek Ministry of Education, Italian Association for Research on Cancer, Italian National Research Council, Dutch Ministry of Public Health, Welfare, and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands, Swedish Cancer, Swedish Scientific Council, Regional Government of Skåne and Västerbotten, Sweden, Norwegian Cancer Society, Research Council of Norway, French League against Cancer, INSERM, Mutuelle Generale l'Education National, and IGR. The EPIC‐Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC‐UU_12015/1) and Cancer Research UK (C864/A14136)., and 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)
Subjects: 0301 basic medicine, Adult, Male, Risk, medicine.medical_specialty, Clinical Neurology, Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, LEAD-EXPOSURE, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Research Articles, POPULATION, Aged, Retrospective Studies, Science & Technology, Neurology & Neurosurgery, business.industry, Amyotrophic Lateral Sclerosis, Neurosciences, 1103 Clinical Sciences, Retrospective cohort study, Odds ratio, Environmental exposure, Environmental Exposure, Mercury, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030104 developmental biology, Neurology, Cohort, Population study, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurosciences & Neurology, Neurology (clinical), SMOKING, 1109 Neurosciences, business, Life Sciences & Biomedicine, 030217 neurology & neurosurgery, Research Article, Cohort study
Abstract: International audience; Objective: Metals have been suggested as a risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality. Methods: A nested ALS case–control study was conducted within the prospective EPIC (European Prospective Investigation into Cancer and Nutrition) cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as a biomarker for metal exposure from any source. Arsenic, cadmium, copper, lead, manganese, mercury, selenium, and zinc concentrations were measured by inductively coupled plasma–mass spectrometry. To estimate ALS risk, we applied conditional logistic regression models. Results: The study population comprised 107 cases (65% female) and 319 controls matched for age, sex, and study center. Median time between blood collection and ALS death was 8 years (range = 1–15). Comparing the highest with the lowest tertile, cadmium (odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.08–3.87) and lead (OR = 1.89, 95% CI = 0.97–3.67) concentrations suggest associations with increased ALS risk. Zinc was associated with a decreased risk (OR = 0.50, 95% CI = 0.27–0.94). Associations for cadmium and lead remained when limiting analyses to noncurrent smokers. Interpretation: This is the first study to compare metal levels before disease onset, minimizing reverse causation. The observed associations suggest that cadmium, lead, and zinc may play a role in ALS etiology. Cadmium and lead possibly act as intermediates on the pathway from smoking to ALS. ANN NEUROL 20209999:n/a–n/a.
Published: 2021

10. Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan

Author: Hollis, Ben, Day, Felix R., Busch, Alexander S., Thompson, Deborah J., Soares, Ana Luiza G., Timmers, Paul R.H.J., Kwong, Alex, Easton, Doug F., Joshi, Peter K., Timpson, Nicholas J., Eeles, Rosalind A., Henderson, Brian E., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Olama, Ali Amin Al, Benlloch, Sara, Muir, Kenneth, Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Gapstur, Susan, Stevens, Victoria L., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Cancel-Tassin, Géraldine, Koutros, Stella, Sorensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Nordestgaard, Børge G., Day, Felix R [0000-0003-3789-7651], Busch, Alexander S [0000-0003-4417-569X], Thompson, Deborah J [0000-0003-1465-5799], Soares, Ana Luiza G [0000-0003-2763-4647], Timmers, Paul R H J [0000-0002-5197-1267], Kwong, Alex [0000-0003-1953-2771], Easton, Doug F [0000-0003-2444-3247], Joshi, Peter K [0000-0002-6361-5059], Timpson, Nicholas J [0000-0002-7141-9189], Ong, Ken K [0000-0003-4689-7530], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, Time Factors, General Physics and Astronomy, Physiology, Genome-wide association study, Genome-wide association studies, Cohort Studies, 0302 clinical medicine, Endocrinology, Genetics research, Sexual Maturation, Young adult, lcsh:Science, RISK, Multidisciplinary, Age Factors, Mendelian Randomization Analysis, Effective sample size, Multidisciplinary Sciences, Pituitary hormones, Science & Technology - Other Topics, Female, Adult, Science, Longevity, Reproductive biology, Biology, Health outcomes, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, MENARCHE, 03 medical and health sciences, Young Adult, AGE, Mendelian randomization, Humans, Hair Color, Genetic association, Menarche, Science & Technology, MUTATIONS, Puberty, General Chemistry, 030104 developmental biology, METASTASIS, PIGMENTATION, lcsh:Q, 030217 neurology & neurosurgery, SKIN, Genome-Wide Association Study
Abstract: The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes., Age at voice-breaking is used to determine puberty timing in men, recall of which is considered less accurate than age at first menarche in women. Here, the authors perform multi-trait GWAS for male puberty timing by including both age at voice breaking and age of first facial hair for improved phenotype definition and power.
Published: 2020
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11. Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study

Author: Dossus, Laure, Franceschi, Silvia, Biessy, Carine, Navionis, Anne-Sophie, Travis, Ruth C, Weiderpass, Elisabete, Scalbert, Augustin, Romieu, Isabelle, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Boutron-Ruault, Marie-Christine, Bonnet, Fabrice, Fournier, Agnès, Fortner, Renee T, Kaaks, Rudolf, Aleksandrova, Krasimira, Trichopoulou, Antonia, La Vecchia, Carlo, Peppa, Eleni, Tumino, Rosario, Panico, Salvatore, Palli, Domenico, Agnoli, Claudia, Vineis, Paolo, Bueno-de-Mesquita, Bas, Peeters, Petra H, Skeie, Guri, Zamora-Ros, Raul, Chirlaque, María-Dolores, Ardanaz, Eva, Sánchez, Maria-Jose, Quirós, Jose Ramón, Dorronsoro, Miren, Sandström, Maria, Nilsson, Lena Maria, Schmidt, Julie A, Khaw, Kay-Tee, Tsilidis, Konstantinos K, Aune, Dagfinn, Riboli, Elio, Rinaldi, Sabina, Institut National du Cancer, Dossus, Laure, Franceschi, Silvia, Biessy, Carine, Navionis, Anne-Sophie, Travis, Ruth C., Weiderpass, Elisabete, Scalbert, Augustin, Romieu, Isabelle, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Boutron-Ruault, Marie-Christine, Bonnet, Fabrice, Fournier, Agnè, Fortner, Renee T., Kaaks, Rudolf, Aleksandrova, Krasimira, Trichopoulou, Antonia, La Vecchia, Carlo, Peppa, Eleni, Tumino, Rosario, Panico, Salvatore, Palli, Domenico, Agnoli, Claudia, Vineis, Paolo, Bueno-de-Mesquita, H. Ba, Peeters, Petra H., Skeie, Guri, Zamora-Ros, Raul, Chirlaque, María-Dolore, Ardanaz, Eva, Sánchez, Maria-Jose, Ramón Quirós, Jose, Dorronsoro, Miren, Sandström, Maria, Nilsson, Lena Maria, Schmidt, Julie A., Khaw, Kay-Tee, Tsilidis, Konstantinos K., Aune, Dagfinn, Riboli, Elio, and Rinaldi, Sabina
Subjects: Adult, Male, Cancer Research, GENE POLYMORPHISM, BIOMARKERS, prospective cohort, Body Mass Index, POOLED ANALYSIS, Adipokines, Risk Factors, Journal Article, Biomarkers, Tumor, Càncer de tiroide, thyroid cancer, cytokine, Humans, BREAST-CANCER, Prospective Studies, Thyroid Neoplasms, Oncology & Carcinogenesis, Obesity, Aged, ENDOMETRIAL CANCER-RISK, Science & Technology, adipokine, Interleukin-6, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Incidence, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, INTERLEUKIN-10, C-REACTIVE PROTEIN, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, ADIPOSE-TISSUE, Oncology, inflammation, Case-Control Studies, Thyroid gland cancer, PLASMA ADIPONECTIN CONCENTRATIONS, Obesitat, Female, CIRCULATING ADIPONECTIN, Adiponectin, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis
Abstract: Source at https://doi.org/10.1002/ijc.31172. Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C‐reactive protein, interleukin (IL)‐6, IL‐10 and tumor necrosis factor (TNF)‐α and the risk of TC. A case‐control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer‐free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (ORT3vs.T1 = 0.69, 95% CI: 0.49–0.98, Ptrend = 0.04) but not among men (ORT3vs.T1 = 1.36, 95% CI: 0.67–2.76, Ptrend = 0.37). Increasing levels of IL‐10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1 = 1.59, 95% CI: 1.13–2.25, Ptrend = 0.01) but not in men (ORT3vs.T1 = 1.78, 95% CI: 0.80–3.98, Ptrend = 0.17). Leptin, CRP, IL‐6 and TNF‐α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL‐10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight.
Published: 2017

12. Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Author: Duell, Eric J, Lujan-Barroso, Leila, Sala, Núria, Deitz McElyea, Samantha, Overvad, Kim, Tjonneland, Anne, Olsen, Anja, Weiderpass, Elisabete, Busund, Lill-Tove, Moi, Line, Muller, David C, Vineis, Paolo, Aune, Dagfinn, Matullo, Giuseppe, Naccarati, Alessio, Panico, Salvatore, Tagliabue, Giovanna, Tumino, Rosario, Palli, Domenico, Kaaks, Rudolf, Katzke, Verena A, Boeing, Heiner, Bueno-de-Mesquita, HBA, Peeters, Petra H, Trichopoulou, Antonia, Lagiou, Pagona, Kotanidou, Anastasia, Travis, Ruth C, Wareham, Nick, Khaw, Kay-Tee, Ramon Quirós, Jose, Rodríguez-Barranco, Miguel, Dorronsoro, Miren, Chirlaque, Maria-Dolores, Ardanaz, Eva, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Rebours, Vinciane, Brennan, Paul, Gunter, Marc, Scelo, Ghislaine, Cote, Greg, Sherman, Stuart, Korc, Murray, Duell, Eric J., Lujan barroso, Leila, Sala, Nãºria, Deitz Mcelyea, Samantha, Overvad, Kim, Tjonneland, Anne, Olsen, Anja, Weiderpass, Elisabete, Busund, Lill tove, Moi, Line, Muller, David, Vineis, Paolo, Aune, Dagfinn, Matullo, Giuseppe, Naccarati, Alessio, Panico, Salvatore, Tagliabue, Giovanna, Tumino, Rosario, Palli, Domenico, Kaaks, Rudolf, Katzke, Verena A., Boeing, Heiner, Bueno de mesquita, H. Ba, Peeters, Petra H., Trichopoulou, Antonia, Lagiou, Pagona, Kotanidou, Anastasia, Travis, Ruth C., Wareham, Nick, Khaw, Kay tee, Ramon Quiros, Jose, Rodrãguez barranco, Miguel, Dorronsoro, Miren, Chirlaque, Marãa dolore, Ardanaz, Eva, Severi, Gianluca, Boutron ruault, Marie christine, Rebours, Vinciane, Brennan, Paul, Gunter, Marc, Scelo, Ghislaine, Cote, Greg, Sherman, Stuart, and Korc, Murray
Subjects: Male, Cancer Research, PROMOTES, pancreatic cancer, MICROENVIRONMENT, Polymerase Chain Reaction, cohort studies, Prospective Studies, Medicine(all), microRNA, Medicine (all), Pancreatic Neoplasm, Middle Aged, microRNAs, Oncology, Area Under Curve, SURVIVAL, biomarker, Cohort studies, Female, Case-Control Studie, Life Sciences & Biomedicine, Human, Carcinoma, Pancreatic Ductal, EXPRESSION, Adult, DUCTAL ADENOCARCINOMA, DIAGNOSIS, Sensitivity and Specificity, Article, POOR-PROGNOSIS, Biomarkers, Tumor, Journal Article, Humans, Oncology & Carcinogenesis, Biomarkers, MicroRNAs, Pancreatic cancer, Aged, Science & Technology, biomarkers, EVOLUTION, Pancreatic Neoplasms, Prospective Studie, ROC Curve, Case-Control Studies, CELLS, PATTERNS, 1112 Oncology And Carcinogenesis, cohort studie
Abstract: Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155 and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p-values
Published: 2017

13. Mortality in vegetarians and comparable nonvegetarians in the United Kingdom123

Author: Appleby, Paul N, Crowe, Francesca L, Bradbury, Kathryn E, Travis, Ruth C, and Key, Timothy J
Subjects: vegan, Adult, Male, Risk, Meat, Respiratory Tract Diseases, Body Mass Index, Eating, Nutritional Epidemiology and Public Health, Cause of Death, Neoplasms, Animals, Humans, nonvegetarian, Proportional Hazards Models, vegetarian, Diet, Vegetarian, Feeding Behavior, Middle Aged, mortality, Carnivory, United Kingdom, Diet, Cardiovascular Diseases, Female, Vegetarians
Abstract: Background: Vegetarians and others who do not eat meat have been observed to have lower incidence rates than meat eaters of some chronic diseases, but it is unclear whether this translates into lower mortality. Objective: The purpose of this study was to describe mortality in vegetarians and comparable nonvegetarians in a large United Kingdom cohort. Design: The study involved a pooled analysis of data from 2 prospective studies that included 60,310 persons living in the United Kingdom, comprising 18,431 regular meat eaters (who ate meat ≥5 times/wk on average), 13,039 low (less-frequent) meat eaters, 8516 fish eaters (who ate fish but not meat), and 20,324 vegetarians (including 2228 vegans who did not eat any animal foods). Mortality by diet group for each of 18 common causes of death was estimated with the use of Cox proportional hazards models. Results: There were 5294 deaths before age 90 in >1 million y of follow-up. There was no significant difference in overall (all-cause) mortality between the diet groups: HRs in low meat eaters, fish eaters, and vegetarians compared with regular meat eaters were 0.93 (95% CI: 0.86, 1.00), 0.96 (95% CI: 0.86, 1.06), and 1.02 (95% CI: 0.94, 1.10), respectively; P-heterogeneity of risks = 0.082. There were significant differences in risk compared with regular meat eaters for deaths from circulatory disease [higher in fish eaters (HR: 1.22; 95% CI: 1.02, 1.46)]; malignant cancer [lower in fish eaters (HR: 0.82; 95% CI: 0.70, 0.97)], including pancreatic cancer [lower in low meat eaters and vegetarians (HR: 0.55; 95% CI: 0.36, 0.86 and HR: 0.48; 95% CI: 0.28, 0.82, respectively)] and cancers of the lymphatic/hematopoietic tissue [lower in vegetarians (HR: 0.50; 95% CI: 0.32, 0.79)]; respiratory disease [lower in low meat eaters (HR: 0.70; 95% CI: 0.53, 0.92)]; and all other causes [lower in low meat eaters (HR: 0.74; 95% CI: 0.56, 0.99)]. Further adjustment for body mass index left these associations largely unchanged. Conclusions: United Kingdom–based vegetarians and comparable nonvegetarians have similar all-cause mortality. Differences found for specific causes of death merit further investigation.
Published: 2015

14. Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels: Results from the EPIC cohort

Author: Fortner, Renée T, Schock, Helena, Le Cornet, Charlotte, Hüsing, Anika, Vitonis, Allison F, Johnson, Theron S, Fichorova, Raina N, Fashemi, Titilayo, Yamamoto, Hidemi S, Tjønneland, Anne, Hansen, Louise, Overvad, Kim, Boutron-Ruault, Marie-Christine, Kvaskoff, Marina, Severi, Gianluca, Boeing, Heiner, Trichopoulou, Antonia, Papatesta, Eleni-Maria, La Vecchia, Carlo, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Sacerdote, Carlotta, Mattiello, Amalia, Onland-Moret, N Charlotte, Peeters, Petra H, Bueno-de-Mesquita, H B As, Weiderpass, Elisabete, Quirós, J Ramón, Duell, Eric J, Sánchez, Maria-Jose, Navarro, Carmen, Ardanaz, Eva, Larrañaga, Nerea, Nodin, Björn, Jirström, Karin, Idahl, Annika, Lundin, Eva, Khaw, Kay-Tee, Travis, Ruth C, Gunter, Marc, Johansson, Mattias, Dossus, Laure, Merritt, Melissa A, Riboli, Elio, Terry, Kathryn L, Cramer, Daniel W, and Kaaks, Rudolf
Subjects: Adult, anti-CA125 antibodies, endocrine system diseases, autoantibodies, MUC16, BIOMARKERS, DIAGNOSIS, Sensitivity and Specificity, Article, Cohort Studies, CA125, Biomarkers, Tumor, Journal Article, Humans, Oncology & Carcinogenesis, TUMOR-ASSOCIATED ANTIGENS, Early Detection of Cancer, Aged, Autoantibodies, Ovarian Neoplasms, Science & Technology, Membrane Proteins, Middle Aged, female genital diseases and pregnancy complications, ovarian cancer, Oncology, ROC Curve, Area Under Curve, CA-125 Antigen, Case-Control Studies, IMMUNE-COMPLEXES, Female, early detection markers, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis, LUNG
Abstract: CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to 4 matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated towards the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed
Published: 2018

15. Fiber intake modulates the association of alcohol intake with breast cancer

Author: Romieu, Isabelle, Ferrari, Pietro, Chajès, Veronique, de Batlle, Jordi, Biessy, Carine, Scoccianti, Chiara, Dossus, Laure, Boutron, Marie Christine, Bastide, Nadia, Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Kaaks, Rudolf, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Vineis, Paolo, Bueno de Mesquita, H. B. As, Gils, Carla H, Peeters, Petra H, Lund, Eiliv, Skeie, Guri, Weiderpass, Elisabete, Quirós, J. Ramón, Chirlaque, María Dolores, Ardanaz, Eva, Sánchez, María José, Duell, Eric J, Amiano Etxezarreta, Pilar, Borgquist, Signe, Hallmans, Göran, Johansson, Ingegerd, Nilsson, Lena Maria, Khaw, Kay Tee, Wareham, Nick, Key, Timothy J, Travis, Ruth C, Murphy, Neil, Wark, Petra A, Riboli, Elio, PANICO, SALVATORE, University Medical Center Utrecht, Imperial College Trust, Romieu, Isabelle, Ferrari, Pietro, Chajès, Veronique, de Batlle, Jordi, Biessy, Carine, Scoccianti, Chiara, Dossus, Laure, Boutron, Marie Christine, Bastide, Nadia, Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Kaaks, Rudolf, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. B. A, Gils, Carla H, Peeters, Petra H, Lund, Eiliv, Skeie, Guri, Weiderpass, Elisabete, Quirós, J. Ramón, Chirlaque, María Dolore, Ardanaz, Eva, Sánchez, María José, Duell, Eric J, Amiano Etxezarreta, Pilar, Borgquist, Signe, Hallmans, Göran, Johansson, Ingegerd, Nilsson, Lena Maria, Khaw, Kay Tee, Wareham, Nick, Key, Timothy J, Travis, Ruth C, Murphy, Neil, Wark, Petra A, and Riboli, Elio
Subjects: Adult, Dietary Fiber, Cancer Research, Alcohol Drinking, Breast Neoplasms, Article, breast cancer, Risk Factors, Vegetables, Journal Article, Humans, Oncology & Carcinogenesis, Prospective Studies, Life Style, Aged, Proportional Hazards Models, Medicine(all), Ethanol, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, alcohol, Estrogens, Middle Aged, Diet, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, nutrition, Oncology, Female, epidemiology, 1112 Oncology And Carcinogenesis
Abstract: Accepted manuscript version. Published version available at https://doi.org/10.1002/ijc.30415. Alcohol intake has been related to an increased risk of breast cancer (BC) while dietary fiber intake has been inversely associated to BC risk. A beneficial effect of fibers on ethanol carcinogenesis through their impact on estrogen levels is still controversial. We investigated the role of dietary fiber as a modifying factor of the association of alcohol and BC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). This study included 334,850 women aged 35–70 years at baseline enrolled in the ten countries of the EPIC study and followed up for 11.0 years on average. Information on fiber and alcohol intake at baseline and average lifetime alcohol intake were calculated from country‐specific dietary and lifestyle questionnaires. Hazard ratios (HR) of developing invasive BC according to different levels of alcohol and fiber intake were computed. During 3,670,439 person‐years, 11,576 incident BC cases were diagnosed. For subjects with low intake of fiber (24.2 g/day) the risk of BC was 1.02 (0.99–1.05) (test for interaction p = 0.011). This modulating effect was stronger for fiber from vegetables. Our results suggest that fiber intake may modulate the positive association of alcohol intake and BC. Alcohol is well known to increase the risk for BC, while a fiber‐rich diet has the opposite effect. Here the authors find a significant interaction between both lifestyle factors indicating that high fiber intake can ease the adverse effects associated with alcohol consumption. Consequently, women with high alcohol intake and low fiber intake (
Published: 2016

16. Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers : Findings from a prospective cohort study

Author: Stepien, Magdalena, Duarte Salles, Talita, Fedirko, Veronika, Floegel, Anne, Barupal, Dinesh Kumar, Rinaldi, Sabina, Achaintre, David, Assi, Nada, Tjønneland, Anne, Overvad, Kim, Bastide, Nadia, Boutron Ruault, Marie Christine, Severi, Gianluca, Kühn, Tilman, Kaaks, Rudolf, Aleksandrova, Krasimira, Boeing, Heiner, Trichopoulou, Antonia, Bamia, Christina, Lagiou, Pagona, Saieva, Calogero, Agnoli, Claudia, Tumino, Rosario, Naccarati, Alessio, Bueno de Mesquita, H. B. As, Peeters, Petra H, Weiderpass, Elisabete, Quirós, J. Ramón, Agudo, Antonio, Sánchez, María José, Dorronsoro, Miren, Gavrila, Diana, Barricarte, Aurelio, Ohlsson, Bodil, Sjöberg, Klas, Werner, Mårten, Sund, Malin, Wareham, Nick, Khaw, Kay Tee, Travis, Ruth C, Schmidt, Julie A, Gunter, Marc, Cross, Amanda, Vineis, Paolo, Romieu, Isabelle, Scalbert, Augustin, Jenab, Mazda, PANICO, SALVATORE, Stepien, Magdalena, Duarte Salles, Talita, Fedirko, Veronika, Floegel, Anne, Barupal, Dinesh Kumar, Rinaldi, Sabina, Achaintre, David, Assi, Nada, Tjønneland, Anne, Overvad, Kim, Bastide, Nadia, Boutron Ruault, Marie Christine, Severi, Gianluca, Kühn, Tilman, Kaaks, Rudolf, Aleksandrova, Krasimira, Boeing, Heiner, Trichopoulou, Antonia, Bamia, Christina, Lagiou, Pagona, Saieva, Calogero, Agnoli, Claudia, Panico, Salvatore, Tumino, Rosario, Naccarati, Alessio, Bueno de Mesquita, H. B. A, Peeters, Petra H, Weiderpass, Elisabete, Quirós, J. Ramón, Agudo, Antonio, Sánchez, María José, Dorronsoro, Miren, Gavrila, Diana, Barricarte, Aurelio, Ohlsson, Bodil, Sjöberg, Kla, Werner, Mårten, Sund, Malin, Wareham, Nick, Khaw, Kay Tee, Travis, Ruth C, Schmidt, Julie A, Gunter, Marc, Cross, Amanda, Vineis, Paolo, Romieu, Isabelle, Scalbert, Augustin, and Jenab, Mazda
Subjects: Male, Biogenic Amines, Cancer Research, Carcinoma, Hepatocellular, Hepatocellular carcinoma, Biliary tract cancers, Biogenic Amine, Cohort Studies, Bile Ducts, Extrahepatic, biliary tract cancer, Odds Ratio, Journal Article, Humans, Prospective Studies, Amino Acids, Bile Duct Neoplasm, Gallbladder Neoplasm, Aged, Liver Neoplasms, targeted metabolomic, Targeted metabolomics, Middle Aged, Prospective cohort, Amino Acid, Prospective Studie, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, ROC Curve, Oncology, Liver Neoplasm, Area Under Curve, Case-Control Studies, Amino acids, Female, Gallbladder Neoplasms, Cohort Studie, Case-Control Studie, Human
Abstract: Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development.
Published: 2016

17. Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

Author: Perez-Cornago, Aurora, Appleby, Paul N, Tipper, Sarah, Key, Timothy J., Allen, Naomi E., Nieters, Alexandra, Vermeulen, Roel, Roulland, Sandrine, Casabonne, Delphine, Kaaks, Rudolf, Fortner, Renee T, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Klinaki, Eleni, Hansen, Louise, Tjønneland, Anne, Bonnet, Fabrice, Fagherazzi, Guy, Boutron-Ruault, Marie Christine, Pala, Valeria, Masala, Giovanna, Sacerdote, Carlotta, Peeters, Petra H., Bueno-de-Mesquita, H B As, Weiderpass, Elisabete, Dorronsoro, Miren, Quirós, J. Ramón, Barricarte, Aurelio, Gavrila, Diana, Agudo, Antonio, Borgquist, Signe, Rosendahl, Ann H, Melin, Beatrice, Wareham, Nick J, Khaw, Kay-Tee, Gunter, Marc J., Riboli, Elio, Vineis, Paolo, Travis, Ruth C., LS IRAS EEPI GRA (Gezh.risico-analyse), and dIRAS RA-2
Subjects: Adult, Aged, 80 and over, Male, Risk, Lymphoma, Middle Aged, Nutrition Surveys, Europe, Multicenter Study, Socioeconomic Factors, Risk Factors, hemic and lymphatic diseases, Case-Control Studies, Odds Ratio, Journal Article, Humans, Female, Insulin-Like Growth Factor I, Aged, Follow-Up Studies
Abstract: Insulin-like growth factor (IGF)-I has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested case-control study of 1,072 cases of lymphoid malignancies and 1,072 individually matched controls from the European Prospective Investigation into Cancer and Nutrition. Odds ratios (ORs) and confidence intervals (CIs) for lymphoma were calculated using conditional logistic regression. IGF-I concentration was not associated with overall lymphoma risk (multivariable-adjusted OR for highest versus lowest third = 0.77 [95% CI = 0.57-1.03], ptrend = 0.06). There was no statistical evidence of heterogeneity in this association with IGF-I by sex, age at blood collection, time between blood collection and diagnosis, age at diagnosis, or body mass index (pheterogeneity for all ≥ 0.05). There were no associations between IGF-I concentration and risk for specific BCL subtypes, T-cell lymphoma or Hodgkin lymphoma, although number of cases were small. In this European population, IGF-I concentration was not associated with risk of overall lymphoma. This study provides the first prospective evidence on circulating IGF-I concentrations and risk of lymphoma. Further prospective data are required to examine associations of IGF-I concentrations with lymphoma subtypes.
Published: 2017

18. Alcohol consumption and the risk of renal cancers in the European prospective investigation into cancer and nutrition (EPIC)

Author: Wozniak, Magdalena B., Brennan, Paul, Brenner, Darren R., Overvad, Kim, Olsen, Anja, Tjonneland, Anne, Boutron-Ruault, Marie-Christine, Clavel-Chapelon, Francoise, Fagherazzi, Guy, Katzke, Verena, Kuehn, Tilman, Boeing, Heiner, Bergmann, Manuela M., Steffen, Annika, Naska, Androniki, Trichopoulou, Antonia, Trichopoulos, Dimitrios, Saieva, Calogero, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Vineis, Paolo, Bueno-de-Mesquita, H. B(as), Peeters, Petra H., Hjartaker, Anette, Weiderpass, Elisabete, Arriola, Larraitz, Molina-Montes, Esther, Duell, Eric J., Santiuste, Carmen, Alonso de la Torre, Ramon, Barricarte Gurrea, Aurelio, Stocks, Tanja, Johansson, Mattias, Ljungberg, Borje, Wareham, Nick, Khaw, Kay-Tee, Travis, Ruth C., Cross, Amanda J., Murphy, Neil, Riboli, Elio, Scelo, Ghislaine, Imperial College Trust, Wozniak, Magdalena B, Brennan, Paul, Brenner, Darren R, Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Boutron Ruault, Marie Christine, Clavel Chapelon, Françoise, Fagherazzi, Guy, Katzke, Verena, Kühn, Tilman, Boeing, Heiner, Bergmann, Manuela M, Steffen, Annika, Naska, Androniki, Trichopoulou, Antonia, Trichopoulos, Dimitrio, Saieva, Calogero, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Vineis, Paolo, Bueno de Mesquita, H. B. A, Peeters, Petra H, Hjartåker, Anette, Weiderpass, Elisabete, Arriola, Larraitz, Molina Montes, Esther, Duell, Eric J, Santiuste, Carmen, Alonso de la Torre, Ramón, Barricarte Gurrea, Aurelio, Stocks, Tanja, Johansson, Mattia, Ljungberg, Börje, Wareham, Nick, Khaw, Kay Tee, Travis, Ruth C, Cross, Amanda J, Murphy, Neil, Riboli, Elio, and Scelo, Ghislaine
Subjects: Male, COUNTRIES, renal cell carcinoma, Alcohol Drinking, alcohol consumption, DIET, DRINKING, Surveys and Questionnaires, Journal Article, cohort study, Humans, EPIDEMIOLOGY, risk factors, COHORT, Prospective Studies, Oncology & Carcinogenesis, Life Style, METAANALYSIS, Proportional Hazards Models, Science & Technology, KIDNEY CANCER, Risk Factor, FLUID INTAKE, Kidney Neoplasm, WOMEN, kidney cancer, CELL CARCINOMA, Kidney Neoplasms, Europe, Multicenter Study, Prospective Studie, Oncology, Proportional Hazards Model, Female, EPIC, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis, Human
Abstract: Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 through to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n=931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment versus the light drinkers category were 0.78 (0.62-0.99), 0.82 (0.64-1.04), 0.70 (0.55-0.90), 0.91 (0.63-1.30), respectively, (p(trend)=0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer. What's new? Previous studies have indicated that environmental or lifestyle factors may be involved in the etiology of renal cancer, and that moderate alcohol consumption may reduce the risk of this type of cancer. In this very large European study (nearly 500,000 subjects), the authors found that, indeed, total alcohol consumption was inversely associated with renal cancer overall (for all subsites combined), and also with cancers of the renal parenchyma.
Published: 2015

19. Alcohol intake and breast cancer in the European Prospective investigation into Cancer and Nutrition

Author: Romieu, Isabelle, Scoccianti, Chiara, Chajès, Véronique, De Batlle, Jordi, Biessy, Carine, Dossus, Laure, Baglietto, Laura, Clavel-Chapelon, Françoise, Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Kaaks, Rudolf, Lukanova, Annekatrin, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno-De-Mesquita, H. Bas, Van Gils, Carla H., Peeters, Petra H., Lund, Eiliv, Skeie, Guri, Weiderpass, Elisabete, García, José Ramõn Quirõs, Chirlaque, María Dolores, Ardanaz, Eva, Sánchez, María José, Duell, Eric J., Amiano, Pilar, Borgquist, Signe, Wirfält, Elisabet, Hallmans, Göran, Johansson, Ingegerd, Nilsson, Lena Maria, Khaw, Kay Tee, Wareham, Nick, Key, Timothy J., Travis, Ruth C., Murphy, Neil, Wark, Petra A., Ferrari, Pietro, Riboli, Elio, Romieu, Isabelle, Scoccianti, Chiara, Chajès, Véronique, de Batlle, Jordi, Biessy, Carine, Dossus, Laure, Baglietto, Laura, Clavel Chapelon, Françoise, Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Kaaks, Rudolf, Lukanova, Annekatrin, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. B. A, van Gils, Carla H, Peeters, Petra H, Lund, Eiliv, Skeie, Guri, Weiderpass, Elisabete, Quirós García, José Ramón, Chirlaque, María Dolore, Ardanaz, Eva, Sánchez, María José, Duell, Eric J, Amiano, Pilar, Borgquist, Signe, Wirfält, Elisabet, Hallmans, Göran, Johansson, Ingegerd, Nilsson, Lena Maria, Khaw, Kay Tee, Wareham, Nick, Key, Timothy J, Travis, Ruth C, Murphy, Neil, Wark, Petra A, Ferrari, Pietro, Riboli, Elio, and Commission of the European Communities
Subjects: Adult, Cancer Research, Alcohol Drinking, Receptor, ErbB-2, alcohol consumption, Breast Neoplasms, Article, breast cancer, DRINKING, HORMONE-RECEPTOR STATUS, Risk Factors, Surveys and Questionnaires, Journal Article, Humans, Prospective Studies, Oncology & Carcinogenesis, Proportional Hazards Models, Aged, RISK, Science & Technology, Medicine (all), Risk Factor, CONSUMPTION, Middle Aged, ESTROGEN-RECEPTORS, Europe, Postmenopause, Prospective Studie, POSTMENOPAUSAL WOMEN, Receptors, Estrogen, Oncology, PREMENOPAUSAL WOMEN, Proportional Hazards Model, Female, prospective study, HEALTH, Receptors, Progesterone, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis, Breast Neoplasm, Human
Abstract: Alcohol intake has been associated to breast cancer in pre and postmenopausal women; however results are inconclusive regarding tumor hormonal receptor status, and potential modifying factors like age at start drinking. Therefore, we investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Up to 334,850 women, aged 35–70 years at baseline, were recruited in ten European countries and followed up an average of 11 years. Alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. The study outcomes were the Hazard ratios (HR) of developing breast cancer according to hormonal receptor status. During 3,670,439 person-years, 11,576 incident breast cancer cases were diagnosed. Alcohol intake was significantly related to breast cancer risk, for each 10 g/day increase in alcohol intake the HR increased by 4.2% (95% CI: 2.7–5.8%). Taking 0 to 5 g/day as reference, alcohol intake of >5 to 15 g/day was related to a 5.9% increase in breast cancer risk (95% CI: 1–11%). Significant increasing trends were observed between alcohol intake and ER1/ PR1, ER2/PR2, HER22 and ER2/PR2HER22 tumors. Breast cancer risk was stronger among women who started drinking prior to first full-time pregnancy. Overall, our results confirm the association between alcohol intake and both hormone receptor positive and hormone receptor negative breast tumors, suggesting that timing of exposure to alcohol drinking may affect the risk. Therefore, women should be advised to control their alcohol consumption. What’s new? Although it is now established that alcohol consumption increases breast cancer risk, many questions remain. Using a prospective study design with 11,576 incident breast cancer cases across 10 European countries, the authors confirmed the increased risk of alcohol on breast cancer development. They further show that women who started drinking before their first full-term pregnancy have a higher risk than women who started afterwards. These effects were observed in hormone-receptor positive and –negative tumors pointing to non-hormonal pathways that need to be further investigated.
Published: 2015

20. Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort

Author: Duarte Salles, Talita, Fedirko, Veronika, Stepien, Magdalena, Aleksandrova, Krasimira, Bamia, Christina, Lagiou, Pagona, Laursen, Anne Sofie Dam, Hansen, Louise, Overvad, Kim, Tjønneland, Anne, Boutron Ruault, Marie Christine, Fagherazzi, Guy, His, Mathilde, Boeing, Heiner, Katzke, Verena, Kühn, Tilman, Trichopoulou, Antonia, Valanou, Elissavet, Kritikou, Maria, Masala, Giovanna, Sieri, Sabina, Ricceri, Fulvio, Tumino, Rosario, Bueno de Mesquita, H. B. As, Peeters, Petra H, Hjartåker, Anette, Skeie, Guri, Weiderpass, Elisabete, Ardanaz, Eva, Bonet, Catalina, Chirlaque, Maria Dolores, Dorronsoro, Miren, Quirós, J. Ramón, Johansson, Ingegerd, Ohlsson, Bodil, Sjöberg, Klas, Wennberg, Maria, Khaw, Kay Tee, Travis, Ruth C, Wareham, Nick, Ferrari, Pietro, Freisling, Heinz, Romieu, Isabelle, Cross, Amanda J, Gunter, Marc, Lu, Yunxia, Jenab, Mazda, PANICO, SALVATORE, Duarte Salles, Talita, Fedirko, Veronika, Stepien, Magdalena, Aleksandrova, Krasimira, Bamia, Christina, Lagiou, Pagona, Laursen, Anne Sofie Dam, Hansen, Louise, Overvad, Kim, Tjønneland, Anne, Boutron Ruault, Marie Christine, Fagherazzi, Guy, His, Mathilde, Boeing, Heiner, Katzke, Verena, Kühn, Tilman, Trichopoulou, Antonia, Valanou, Elissavet, Kritikou, Maria, Masala, Giovanna, Panico, Salvatore, Sieri, Sabina, Ricceri, Fulvio, Tumino, Rosario, Bueno de Mesquita, H. B. A, Peeters, Petra H, Hjartåker, Anette, Skeie, Guri, Weiderpass, Elisabete, Ardanaz, Eva, Bonet, Catalina, Chirlaque, Maria Dolore, Dorronsoro, Miren, Quirós, J. Ramón, Johansson, Ingegerd, Ohlsson, Bodil, Sjöberg, Kla, Wennberg, Maria, Khaw, Kay Tee, Travis, Ruth C, Wareham, Nick, Ferrari, Pietro, Freisling, Heinz, Romieu, Isabelle, Cross, Amanda J, Gunter, Marc, Lu, Yunxia, and Jenab, Mazda
Subjects: Male, Cancer Research, European populations, Risk Factors, Surveys and Questionnaires, Surveys and Questionnaire, Prospective Studies, INDEX, Incidence, Liver Neoplasms, hepatocellular carcinoma, Middle Aged, CANCER, NUTRITIONAL EPIDEMIOLOGY, MEDITERRANEAN DIET, Europe, Nutritional Statu, Oncology, Liver Neoplasm, dietary fat, Female, Case-Control Studie, Life Sciences & Biomedicine, Human, Adult, Risk, Carcinoma, Hepatocellular, cohort study, dietary fats, Aged, Case-Control Studies, Diet, Dietary Fats, Feeding Behavior, Humans, Life Style, Nutritional Status, Young Adult, FISH, INFLAMMATION, LIVER-DISEASE, Oncology & Carcinogenesis, METAANALYSIS, Science & Technology, Risk Factor, Carcinoma, Hepatocellular, ACIDS, digestive system diseases, Prospective Studie, Food Habit, RISK-FACTORS, European population, Food Habits, 1112 Oncology And Carcinogenesis
Abstract: The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk. What's new? The rise of hepatocellular carcinoma (HCC) incidence in high- and middle-income countries, where relatively high-fat diets are common, suggests a possible etiological role for dietary fat. In the present study, potential associations between HCC and total fat intake, intake of fat subtypes and intake of fat from different sources were explored with data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Total fat intake, where monounsaturated fats predominated, was inversely associated with HCC risk. By contrast, no risk associations were detected for polyunsaturated or saturated fat intake or fat source.
Published: 2015

21. Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women : the European Prospective Investigation into Cancer and Nutrition Study (EPIC)

Author: Ekelund, Ulf, Ward, Heather A, Norat, Teresa, Luan, Jian'An, May, Anne M, Weiderpass, Elisabete, Sharp, Stephen J, Overvad, Kim, Østergaard, Jane Nautrup, Tjønneland, Anne, Johnsen, Nina Føns, Mesrine, Sylvie, Fournier, Agnès, Fagherazzi, Guy, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Li, Kuanrong, Kaaks, Rudolf, Ferrari, Pietro, Licaj, Idlir, Jenab, Mazda, Bergmann, Manuela, Boeing, Heiner, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Vineis, Paolo, Peeters, Petra H, Monnikhof, Evelyn, Bueno de Mesquita, H. Bas, Quirós, J. Ramón, Agudo, Antonio, Sánchez, María José, Huerta, José María, Ardanaz, Eva, Arriola, Larraitz, Hedblad, Bo, Wirfält, Elisabet, Sund, Malin, Johansson, Mattias, Key, Timothy J, Travis, Ruth C, Khaw, Kay Tee, Brage, Søren, Wareham, Nicholas J, Riboli, Elio, PANICO, SALVATORE, Imperial College Trust, Luan, Jian'an [0000-0003-3137-6337], Sharp, Stephen [0000-0003-2375-1440], Khaw, Kay-Tee [0000-0002-8802-2903], Brage, Soren [0000-0002-1265-7355], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Ekelund, Ulf, Ward, Heather A, Norat, Teresa, Luan, Jian'An, May, Anne M, Weiderpass, Elisabete, Sharp, Stephen J, Overvad, Kim, Østergaard, Jane Nautrup, Tjønneland, Anne, Johnsen, Nina Føn, Mesrine, Sylvie, Fournier, Agnè, Fagherazzi, Guy, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Li, Kuanrong, Kaaks, Rudolf, Ferrari, Pietro, Licaj, Idlir, Jenab, Mazda, Bergmann, Manuela, Boeing, Heiner, Palli, Domenico, Sieri, Sabina, Panico, Salvatore, Tumino, Rosario, Vineis, Paolo, Peeters, Petra H, Monnikhof, Evelyn, Bueno de Mesquita, H. Ba, Quirós, J. Ramón, Agudo, Antonio, Sánchez, María José, Huerta, José María, Ardanaz, Eva, Arriola, Larraitz, Hedblad, Bo, Wirfält, Elisabet, Sund, Malin, Johansson, Mattia, Key, Timothy J, Travis, Ruth C, Khaw, Kay Tee, Brage, Søren, Wareham, Nicholas J, and Riboli, Elio
Subjects: Male, obesity, physical activity, 09 Engineering, Body Mass Index, Cohort Studies, Hospitals, University, Risk Factors, PARTICIPANTS, LIFE EXPECTANCY, Prospective Studies, Adiposity, RISK, Sex Characteristics, Nutrition and Dietetics, exercise, Public Health, Global Health, Social Medicine and Epidemiology, 11 Medical And Health Sciences, Middle Aged, Europe, population attributable action, Näringslära, CARDIOVASCULAR-DISEASE, Obesity, Abdominal, Female, epidemiology, HEALTH, Waist Circumference, COLLEGE, Life Sciences & Biomedicine, Human, Adult, COUNTRIES, Outpatient Clinics, Hospital, Abdominal Fat, QUESTIONNAIRE, Motor Activity, Follow-Up Studie, cohort study, Humans, VALIDITY, Proportional Hazards Models, Science & Technology, Nutrition & Dietetics, Risk Factor, Sex Characteristic, mortality, Prospective Studie, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Proportional Hazards Model, Self Report, Cohort Studie, population attributable fraction, Follow-Up Studies
Abstract: BACKGROUND: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear.OBJECTIVE: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures.DESIGN: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m(2)) (>30), and WC (≥102 cm for men, ≥88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures.RESULTS: Significant interactions (PA × BMI and PA × WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity.CONCLUSION: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.
Published: 2015

22. Night Shift Work and Breast Cancer Incidence: Three Prospective Studies and Meta-analysis of Published Studies

Author: Travis, Ruth C., Balkwill, Angela, Fensom, Georgina K., Appleby, Paul N., Reeves, Gillian K., Wang, Xiao-Si, Roddam, Andrew W., Gathani, Toral, Peto, Richard, Green, Jane, Key, Timothy J., and Beral, Valerie
Subjects: Adult, Adolescent, Incidence, Personnel Staffing and Scheduling, Breast Neoplasms, Articles, Middle Aged, United Kingdom, Circadian Rhythm, Young Adult, Surveys and Questionnaires, Work Schedule Tolerance, Humans, Female, Prospective Studies, Aged
Abstract: Background: It has been proposed that night shift work could increase breast cancer incidence. A 2007 World Health Organization review concluded, mainly from animal evidence, that shift work involving circadian disruption is probably carcinogenic to humans. We therefore aimed to generate prospective epidemiological evidence on night shift work and breast cancer incidence. Methods: Overall, 522 246 Million Women Study, 22 559 EPIC-Oxford, and 251 045 UK Biobank participants answered questions on shift work and were followed for incident cancer. Cox regression yielded multivariable-adjusted breast cancer incidence rate ratios (RRs) and 95% confidence intervals (CIs) for night shift work vs no night shift work, and likelihood ratio tests for interaction were used to assess heterogeneity. Our meta-analyses combined these and relative risks from the seven previously published prospective studies (1.4 million women in total), using inverse-variance weighted averages of the study-specific log RRs. Results: In the Million Women Study, EPIC-Oxford, and UK Biobank, respectively, 673, 28, and 67 women who reported night shift work developed breast cancer, and the RRs for any vs no night shift work were 1.00 (95% CI = 0.92 to 1.08), 1.07 (95% CI = 0.71 to 1.62), and 0.78 (95% CI = 0.61 to 1.00). In the Million Women Study, the RR for 20 or more years of night shift work was 1.00 (95% CI = 0.81 to 1.23), with no statistically significant heterogeneity by sleep patterns or breast cancer risk factors. Our meta-analysis of all 10 prospective studies included 4660 breast cancers in women reporting night shift work; compared with other women, the combined relative risks were 0.99 (95% CI = 0.95 to 1.03) for any night shift work, 1.01 (95% CI = 0.93 to 1.10) for 20 or more years of night shift work, and 1.00 (95% CI = 0.87 to 1.14) for 30 or more years. Conclusions: The totality of the prospective evidence shows that night shift work, including long-term shift work, has little or no effect on breast cancer incidence.
Published: 2016

23. Cross-cancer genome-wide analysis of lung, ovary, breast, prostate and colorectal cancer reveals novel pleiotropic associations

Author: Fehringer, Gordon, Kraft, Peter, Pharoah, Paul D, Eeles, Rosalind A, Chatterjee, Nilanjan, Schumacher, Fredrick R, Schildkraut, Joellen M, Lindstrom, Sara, Brennan, Paul, Bickeboller, Heike, Houlston, Richard S, Landi, Maria Teresa, Caporaso, Neil, Risch, Angela, Al Olama, Ali Amin, Berndt, Sonja I, Giovannucci, Edward L, Gronberg, Henrik, Kote-Jarai, Zsofia, Ma, Jing, Muir, Kenneth, Stampfer, Meir J, Stevens, Victoria L, Wiklund, Fredrik, Willett, Walter C, Goode, Ellen L, Permuth, Jennifer B, Risch, Harvey A, Reid, Brett M, Bezieau, Stephane, Brenner, Hermann, Chan, Andrew T, Chang-Claude, Jenny, Hudson, Thomas J, Kocarnik, Jonathan K, Newcomb, Polly A, Schoen, Robert E, Slattery, Martha L, White, Emily, Adank, Muriel A, Ahsan, Habibul, Aittomaki, Kristiina, Baglietto, Laura, Blomquist, Carl, Canzian, Federico, Czene, Kamila, dos-Santos-Silva, Isabel, Eliassen, A Heather, Figueroa, Jonine D, Flesch-Janys, Dieter, Fletcher, Olivia, Garcia-Closas, Montserrat, Gaudet, Mia M, Johnson, Nichola, Hall, Per, Hazra, Aditi, Hein, Rebecca, Hofman, Albert, Hopper, John L, Irwanto, Astrid, Johansson, Mattias, Kaaks, Rudolf, Kibriya, Muhammad G, Lichtner, Peter, Liu, Jianjun, Lund, Eiliv, Makalic, Enes, Meindl, Alfons, Muller-Myhsok, Bertram, Muranen, Taru A, Nevanlinna, Heli, Peeters, Petra H, Peto, Julian, Prentice, Ross L, Rahman, Nazneen, Sanchez, Maria Jose, Schmidt, Daniel F, Schmutzler, Rita K, Southey, Melissa C, Tamimi, Rulla, Travis, Ruth C, Turnbull, Clare, Uitterlinden, Andre G, Wang, Zhaoming, Whittemore, Alice S, Yang, Xiaohong R, Zheng, Wei, Buchanan, Daniel D, Casey, Graham, Conti, David V, Edlund, Christopher K, Gallinger, Steven, Haile, Robert W, Jenkins, Mark, Le Marchand, Loic, Li, Li, Lindor, Noralene M, Schmit, Stephanie L, Thibodeau, Stephen N, Woods, Michael O, Rafnar, Thorunn, Gudmundsson, Julius, Stacey, Simon N, Stefansson, Kari, Sulem, Patrick, Chen, Y Ann, Tyrer, Jonathan P, Christiani, David C, Wei, Yongyue, Shen, Hongbing, Hu, Zhibin, Shu, Xiao-Ou, Shiraishi, Kouya, Takahashi, Atsushi, Bosse, Yohan, Obeidat, Ma'en, Nickle, David, Timens, Wim, Freedman, Matthew L, Li, Qiyuan, Seminara, Daniela, Chanock, Stephen J, Gong, Jian, Peters, Ulrike, Gruber, Stephen B, Amos, Christopher I, Sellers, Thomas A, Easton, Douglas F, Hunter, David J, Haiman, Christopher A, Henderson, Brian E, Hung, Rayjean J, OCAC, Consortium, PRACTICAL, Res, Hereditary Breast Ovarian Canc, Transdisciplinary, Colorectal, Canc, African Amer Breast, Canc, African Ancestry Prostate, Medical Oncology, Epidemiology, Internal Medicine, Surgery, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Groningen Research Institute for Asthma and COPD (GRIAC)
Subjects: 0301 basic medicine, Oncology, Male, medicine.medical_specialty, Cancer Research, Lung Neoplasms, SUSCEPTIBILITY LOCI, Genotype, IDENTIFIES 2, Colorectal cancer, Locus (genetics), Genome-wide association study, Breast Neoplasms, Article, 03 medical and health sciences, Prostate cancer, AFRICAN ANCESTRY, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Journal Article, AGGRESSIVE PROSTATE, Humans, GENETIC POLYMORPHISMS, Lung cancer, METAANALYSIS, Ovarian Neoplasms, business.industry, COMMON VARIANTS, Prostatic Neoplasms, CELL CARCINOMA, medicine.disease, RISK LOCI, 3. Good health, 030104 developmental biology, Expression quantitative trait loci, Adenocarcinoma, Female, business, Colorectal Neoplasms, GASTRIC-CANCER, Genome-Wide Association Study
Abstract: Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103–14. ©2016 AACR.
Published: 2016

24. Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Author: Molina-Montes, Esther, Sánchez, María José, Zamora-Ros, Raul, Bueno-de-Mesquita, H. Bas, Wark, Petra A., Obon-Santacana, Mireia, Kühn, Tilman, Katzke, Verena, Travis, Ruth C., Ye, Weimin, Sund, Malin, Naccarati, Alessio, Mattiello, Amalia, Krogh, Vittorio, Martorana, Caterina, Masala, Giovanna, Amiano, Pilar, Huerta, José María, Barricarte, Aurelio, Quirós, José Ramón, Weiderpass, Elisabete, Angell Åsli, Lene, Skeie, Guri, Ericson, Ulrika, Sonestedt, Emily, Peeters, Petra H., Romieu, Isabelle, Scalbert, Augustin, Overvad, Kim, Clemens, Matthias, Boeing, Heiner, Trichopoulou, Antonia, Peppa, Eleni, Vidalis, Pavlos, Khaw, Kay Tee, Wareham, Nick, Olsen, Anja, Tjønneland, Anne, Boutroun-Rualt, Marie Christine, Clavel-Chapelon, Françoise, Cross, Amanda J., Lu, Yunxia, Riboli, Elio, Duell, Eric J., Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
Subjects: Male, Cancer Research, Oncology and Carcinogenesis, pancreatic cancer, Cohort Studies, Rare Diseases, Complementary and Integrative Health, Journal Article, Humans, Oncology & Carcinogenesis, Prospective Studies, Life Style, Nutrition, Cancer, Proportional Hazards Models, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Prevention, lignans, food and beverages, cohort, Middle Aged, Diet Records, Europe, Pancreatic Neoplasms, Multicenter Study, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Oncology, flavonoids, Female, Digestive Diseases, diet, Cancer Epidemiology
Abstract: Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow‐up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center‐stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable‐adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95–1.11 and 1.02; 95% CI: 0.89–1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91–1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort., What's new? Flavonoids and lignans found in plant‐based foods are potent cancer chemopreventive agents but little is known about their effects on pancreatic cancer risk. Here the authors address this question in a large prospective epidemiological study using comprehensively derived dietary data. Their results support growing evidence that there is no association between food‐based consumption of both substances with pancreatic cancer risk.
Published: 2016

25. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

Author: Southey, Melissa C, Goldgar, David E, Winqvist, Robert, Pylkäs, Katri, Couch, Fergus, Tischkowitz, Marc, Foulkes, William D, Dennis, Joe, Michailidou, Kyriaki, van Rensburg, Elizabeth J, Heikkinen, Tuomas, Nevanlinna, Heli, Hopper, John L, Dörk, Thilo, Claes, Kathleen Bm, Reis-Filho, Jorge, Teo, Zhi Ling, Radice, Paolo, Catucci, Irene, Peterlongo, Paolo, Tsimiklis, Helen, Odefrey, Fabrice A, Dowty, James G, Schmidt, Marjanka K, Broeks, Annegien, Hogervorst, Frans B, Verhoef, Senno, Carpenter, Jane, Clarke, Christine, Scott, Rodney J, Fasching, Peter A, Haeberle, Lothar, Ekici, Arif B, Beckmann, Matthias W, Peto, Julian, Dos-Santos-Silva, Isabel, Fletcher, Olivia, Johnson, Nichola, Bolla, Manjeet K, Sawyer, Elinor J, Tomlinson, Ian, Kerin, Michael J, Miller, Nicola, Marme, Federik, Burwinkel, Barbara, Yang, Rongxi, Guénel, Pascal, Truong, Thérèse, Menegaux, Florence, Sanchez, Marie, Bojesen, Stig, Nielsen, Sune F, Flyger, Henrik, Benitez, Javier, Zamora, M Pilar, Perez, Jose Ignacio Arias, Menéndez, Primitiva, Anton-Culver, Hoda, Neuhausen, Susan, Ziogas, Argyrios, Clarke, Christina A, Brenner, Hermann, Arndt, Volker, Stegmaier, Christa, Brauch, Hiltrud, Brüning, Thomas, Ko, Yon-Dschun, Muranen, Taru A, Aittomäki, Kristiina, Blomqvist, Carl, Bogdanova, Natalia V, Antonenkova, Natalia N, Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M, Spurdle, Amanda B, Investigators, kConFab, Australian Ovarian Cancer Study Group, Wauters, Els, Smeets, Dominiek, Beuselinck, Benoit, Floris, Giuseppe, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Olson, Janet E, Vachon, Celine, Pankratz, Vernon S, McLean, Catriona, Haiman, Christopher A, Henderson, Brian E, Schumacher, Fredrick, Le Marchand, Loic, Kristensen, Vessela, Alnæs, Grethe Grenaker, Zheng, Wei, Hunter, David J, Lindstrom, Sara, Hankinson, Susan E, Kraft, Peter, Andrulis, Irene, Knight, Julia A, Glendon, Gord, Mulligan, Anna Marie, Jukkola-Vuorinen, Arja, Grip, Mervi, Kauppila, Saila, Devilee, Peter, Tollenaar, Robert AEM, Seynaeve, Caroline, Hollestelle, Antoinette, Garcia-Closas, Montserrat, Figueroa, Jonine, Chanock, Stephen J, Lissowska, Jolanta, Czene, Kamila, Darabi, Hatef, Eriksson, Mikael, Eccles, Diana M, Rafiq, Sajjad, Tapper, William J, Gerty, Sue M, Hooning, Maartje J, Martens, John WM, Collée, J Margriet, Tilanus-Linthorst, Madeleine, Hall, Per, Li, Jingmei, Brand, Judith S, Humphreys, Keith, Cox, Angela, Reed, Malcolm WR, Luccarini, Craig, Baynes, Caroline, Dunning, Alison M, Hamann, Ute, Torres, Diana, Ulmer, Hans Ulrich, Rüdiger, Thomas, Jakubowska, Anna, Lubinski, Jan, Jaworska, Katarzyna, Durda, Katarzyna, Slager, Susan, Toland, Amanda E, Ambrosone, Christine B, Yannoukakos, Drakoulis, Swerdlow, Anthony, Ashworth, Alan, Orr, Nick, Jones, Michael, González-Neira, Anna, Pita, Guillermo, Alonso, M Rosario, Álvarez, Nuria, Herrero, Daniel, Tessier, Daniel C, Vincent, Daniel, Bacot, Francois, Simard, Jacques, Dumont, Martine, Soucy, Penny, Eeles, Rosalind, Muir, Kenneth, Wiklund, Fredrik, Gronberg, Henrik, Schleutker, Johanna, Nordestgaard, Børge G, Weischer, Maren, Travis, Ruth C, Neal, David, Donovan, Jenny L, Hamdy, Freddie C, Khaw, Kay-Tee, Stanford, Janet L, Blot, William J, Thibodeau, Stephen, Schaid, Daniel J, Kelley, Joseph L, Maier, Christiane, Kibel, Adam S, Cybulski, Cezary, Cannon-Albright, Lisa, Butterbach, Katja, Park, Jong, Kaneva, Radka, Batra, Jyotsna, Teixeira, Manuel R, Kote-Jarai, Zsofia, Olama, Ali Amin Al, Benlloch, Sara, Renner, Stefan P, Hartmann, Arndt, Hein, Alexander, Ruebner, Matthias, Lambrechts, Diether, Van Nieuwenhuysen, Els, Vergote, Ignace, Lambretchs, Sandrina, Doherty, Jennifer A, Rossing, Mary Anne, Nickels, Stefan, Eilber, Ursula, Wang-Gohrke, Shan, Odunsi, Kunle, Sucheston-Campbell, Lara E, Friel, Grace, Lurie, Galina, Killeen, Jeffrey L, Wilkens, Lynne R, Goodman, Marc T, Runnebaum, Ingo, Hillemanns, Peter A, Pelttari, Liisa M, Butzow, Ralf, Modugno, Francesmary, Edwards, Robert P, Ness, Roberta B, Moysich, Kirsten B, du Bois, Andreas, Heitz, Florian, Harter, Philipp, Kommoss, Stefan, Karlan, Beth Y, Walsh, Christine, Lester, Jenny, Jensen, Allan, Kjaer, Susanne Krüger, Høgdall, Estrid, Peissel, Bernard, Bonanni, Bernardo, Bernard, Loris, Goode, Ellen L, Fridley, Brooke L, Vierkant, Robert A, Cunningham, Julie M, Larson, Melissa C, Fogarty, Zachary C, Kalli, Kimberly R, Liang, Dong, Lu, Karen H, Hildebrandt, Michelle AT, Wu, Xifeng, Levine, Douglas A, Dao, Fanny, Bisogna, Maria, Berchuck, Andrew, Iversen, Edwin S, Marks, Jeffrey R, Akushevich, Lucy, Cramer, Daniel W, Schildkraut, Joellen, Terry, Kathryn L, Poole, Elizabeth M, Stampfer, Meir, Tworoger, Shelley S, Bandera, Elisa V, Orlow, Irene, Olson, Sara H, Bjorge, Line, Salvesen, Helga B, van Altena, Anne M, Aben, Katja KH, Kiemeney, Lambertus A, Massuger, Leon FAG, Pejovic, Tanja, Bean, Yukie, Brooks-Wilson, Angela, Kelemen, Linda E, Cook, Linda S, Le, Nhu D, Górski, Bohdan, Gronwald, Jacek, Menkiszak, Janusz, Høgdall, Claus K, Lundvall, Lene, Nedergaard, Lotte, Engelholm, Svend Aage, Dicks, Ed, Tyrer, Jonathan, Campbell, Ian, McNeish, Iain, Paul, James, Siddiqui, Nadeem, Glasspool, Rosalind, Whittemore, Alice S, Rothstein, Joseph H, McGuire, Valerie, Sieh, Weiva, Cai, Hui, Shu, Xiao-Ou, Teten, Rachel T, Sutphen, Rebecca, McLaughlin, John R, Narod, Steven A, Phelan, Catherine M, Monteiro, Alvaro N, Fenstermacher, David, Lin, Hui-Yi, Permuth, Jennifer B, Sellers, Thomas A, Chen, Y Ann, Tsai, Ya-Yu, Chen, Zhihua, Gentry-Maharaj, Aleksandra, Gayther, Simon A, Ramus, Susan J, Menon, Usha, Wu, Anna H, Pearce, Celeste L, Van Den Berg, David, Pike, Malcolm C, Dansonka-Mieszkowska, Agnieszka, Plisiecka-Halasa, Joanna, Moes-Sosnowska, Joanna, Kupryjanczyk, Jolanta, Pharoah, Paul Dp, Song, Honglin, Winship, Ingrid, Chenevix-Trench, Georgia, Giles, Graham G, Tavtigian, Sean V, Easton, Doug F, Milne, Roger L, Clinical Genetics, Neurology, Medical Oncology, Surgery, Erasmus MC other, Clinicum, Department of Obstetrics and Gynecology, Medicum, Kristiina Aittomäki / Principal Investigator, Department of Medical and Clinical Genetics, Department of Oncology, Department of Pathology, HUS Gynecology and Obstetrics, Tischkowitz, Marc [0000-0002-7880-0628], Dennis, Joe [0000-0003-4591-1214], Dunning, Alison [0000-0001-6651-7166], Khaw, Kay-Tee [0000-0002-8802-2903], Amin Al Olama, Ali [0000-0002-7178-3431], Dicks, Ed [0000-0002-0617-0401], Tyrer, Jonathan [0000-0003-3724-4757], Pharoah, Paul [0000-0001-8494-732X], Song, Honglin [0000-0001-5076-7371], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Oncology, Male, Ataxia Telangiectasia Mutated Proteins, prostate-cancer, Prostate cancer, 0302 clinical medicine, brca1, Medizinische Fakultät, Medicine and Health Sciences, skin and connective tissue diseases, Genetics (clinical), Ovarian Neoplasms, education.field_of_study, brca2-interacting protein, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], 1184 Genetics, developmental biology, physiology, Nuclear Proteins, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, PROSTATE-CANCER, Cancer: prostate, Multicenter Study, ovarian-cancer, Centre for Surgical Research, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, ovary [Cancer], Female, Fanconi Anemia Complementation Group N Protein, metaanalysis, Risk, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Population, 3122 Cancers, cancer predisposition, Breast Neoplasms, OVARIAN-CANCER, BRCA2-INTERACTING PROTEIN, Cancer: ovary, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, prostate [Cancer], medicine, Cancer Genetics, Genetics, Journal Article, breast [Cancer], BREAST-CANCER, Humans, Genetic Predisposition to Disease, ddc:610, education, gene, CHEK2, FAMILY REGISTRY, METAANALYSIS, breast-cancer, Genetic Association Studies, business.industry, MUTATIONS, Cancer: breast, Tumor Suppressor Proteins, Case-control study, Cancer, Prostatic Neoplasms, medicine.disease, BRCA1, mutations, GENE, susceptibility loci, Checkpoint Kinase 2, 030104 developmental biology, Relative risk, Case-Control Studies, Mutation, family registry, Ovarian cancer, business
Abstract: Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.Methods: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant.Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants.Conclusions: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
Published: 2016

26. Analysis of heritability and shared heritability based on Genome-Wide Association Studies for 13 Cancer Types

Author: Sampson, Joshua N., Wheeler, William A., Yeager, Meredith, Panagiotou, Orestis, Wang, Zhaoming, Berndt, Sonja I., Lan, Qing, Abnet, Christian C., Amundadottir, Laufey T., Figueroa, Jonine D., Landi, Maria Teresa, Mirabello, Lisa, Savage, Sharon A., Taylor, Philip R., Vivo, Immaculata De, McGlynn, Katherine A., Purdue, Mark P., Rajaraman, Preetha, Adami, Hans-Olov, Ahlbom, Anders, Albanes, Demetrius, Amary, Maria Fernanda, An, She-Juan, Andersson, Ulrika, Andriole, Gerald, Andrulis, Irene L., Angelucci, Emanuele, Ansell, Stephen M., Arici, Cecilia, Armstrong, Bruce K., Arslan, Alan A., Austin, Melissa A., Baris, Dalsu, Barkauskas, Donald A., Bassig, Bryan A., Becker, Nikolaus, Benavente, Yolanda, Benhamou, Simone, Berg, Christine, Van Den Berg, David, Bernstein, Leslie, Bertrand, Kimberly A., Birmann, Brenda M., Black, Amanda, Boeing, Heiner, Boffetta, Paolo, Boutron-Ruault, Marie-Christine, Bracci, Paige M., Brinton, Louise, Brooks-Wilson, Angela R., Bueno-de-Mesquita, H. Bas, Burdett, Laurie, Buring, Julie, Butler, Mary Ann, Cai, Qiuyin, Cancel-Tassin, Geraldine, Canzian, Federico, Carrato, Alfredo, Carreon, Tania, Carta, Angela, Chan, John K. C., Chang, Ellen T., Chang, Gee-Chen, Chang, I-Shou, Chang, Jiang, Chang-Claude, Jenny, Chen, Chien-Jen, Chen, Chih-Yi, Chen, Chu, Chen, Chung-Hsing, Chen, Constance, Chen, Hongyan, Chen, Kexin, Chen, Kuan-Yu, Chen, Kun-Chieh, Chen, Ying, Chen, Ying-Hsiang, Chen, Yi-Song, Chen, Yuh-Min, Chien, Li-Hsin, Chirlaque, María-Dolores, Choi, Jin Eun, Choi, Yi Young, Chow, Wong-Ho, Chung, Charles C., Clavel, Jacqueline, Clavel-Chapelon, Françoise, Cocco, Pierluigi, Colt, Joanne S., Comperat, Eva, Conde, Lucia, Connors, Joseph M., Conti, David, Cortessis, Victoria K., Cotterchio, Michelle, Cozen, Wendy, Crouch, Simon, Crous-Bou, Marta, Cussenot, Olivier, Davis, Faith G., Ding, Ti, Diver, W. Ryan, Dorronsoro, Miren, Dossus, Laure, Duell, Eric J., Ennas, Maria Grazia, Erickson, Ralph L., Feychting, Maria, Flanagan, Adrienne M., Foretova, Lenka, Fraumeni, Joseph F., Freedman, Neal D., Beane Freeman, Laura E., Fuchs, Charles, Gago-Dominguez, Manuela, Gallinger, Steven, Gao, Yu-Tang, Gapstur, Susan M., Garcia-Closas, Montserrat, García-Closas, Reina, Gascoyne, Randy D., Gastier-Foster, Julie, Gaudet, Mia M., Gaziano, J. Michael, Giffen, Carol, Giles, Graham G., Giovannucci, Edward, Glimelius, Bengt, Goggins, Michael, Gokgoz, Nalan, Goldstein, Alisa M., Gorlick, Richard, Gross, Myron, Grubb, Robert, Gu, Jian, Guan, Peng, Gunter, Marc, Guo, Huan, Habermann, Thomas M., Haiman, Christopher A., Halai, Dina, Hallmans, Goran, Hassan, Manal, Hattinger, Claudia, He, Qincheng, He, Xingzhou, Helzlsouer, Kathy, Henderson, Brian, Henriksson, Roger, Hjalgrim, Henrik, Hoffman-Bolton, Judith, Hohensee, Chancellor, Holford, Theodore R., Holly, Elizabeth A., Hong, Yun-Chul, Hoover, Robert N., Horn-Ross, Pamela L., Hosain, G. M. Monawar, Hosgood, H. Dean, Hsiao, Chin-Fu, Hu, Nan, Hu, Wei, Hu, Zhibin, Huang, Ming-Shyan, Huerta, Jose-Maria, Hung, Jen-Yu, Hutchinson, Amy, Inskip, Peter D., Jackson, Rebecca D., Jacobs, Eric J., Jenab, Mazda, Jeon, Hyo-Sung, Ji, Bu-Tian, Jin, Guangfu, Jin, Li, Johansen, Christoffer, Johnson, Alison, Jung, Yoo Jin, Kaaks, Rudolph, Kamineni, Aruna, Kane, Eleanor, Kang, Chang Hyun, Karagas, Margaret R., Kelly, Rachel S., Khaw, Kay-Tee, Kim, Christopher, Kim, Hee Nam, Kim, Jin Hee, Kim, Jun Suk, Kim, Yeul Hong, Kim, Young Tae, Kim, Young-Chul, Kitahara, Cari M., Klein, Alison P., Klein, Robert J., Kogevinas, Manolis, Kohno, Takashi, Kolonel, Laurence N., Kooperberg, Charles, Kricker, Anne, Krogh, Vittorio, Kunitoh, Hideo, Kurtz, Robert C., Kweon, Sun-Seog, LaCroix, Andrea, Lawrence, Charles, Lecanda, Fernando, Lee, Victor Ho Fun, Li, Donghui, Li, Haixin, Li, Jihua, Li, Yao-Jen, Li, Yuqing, Liao, Linda M., Liebow, Mark, Lightfoot, Tracy, Lim, Wei-Yen, Lin, Chien-Chung, Lin, Dongxin, Lindstrom, Sara, Linet, Martha S., Link, Brian K., Liu, Chenwei, Liu, Jianjun, Liu, Li, Ljungberg, Börje, Lloreta, Josep, Lollo, Simonetta Di, Lu, Daru, Lund, Eiluv, Malats, Nuria, Mannisto, Satu, Marchand, Loic Le, Marina, Neyssa, Masala, Giovanna, Mastrangelo, Giuseppe, Matsuo, Keitaro, Maynadie, Marc, McKay, James, McKean-Cowdin, Roberta, Melbye, Mads, Melin, Beatrice S., Michaud, Dominique S., Mitsudomi, Tetsuya, Monnereau, Alain, Montalvan, Rebecca, Moore, Lee E., Mortensen, Lotte Maxild, Nieters, Alexandra, North, Kari E., Novak, Anne J., Oberg, Ann L., Offit, Kenneth, Oh, In-Jae, Olson, Sara H., Palli, Domenico, Pao, William, Park, In Kyu, Park, Jae Yong, Park, Kyong Hwa, Patiño-Garcia, Ana, Pavanello, Sofia, Peeters, Petra H. M., Perng, Reury-Perng, Peters, Ulrike, Petersen, Gloria M., Picci, Piero, Pike, Malcolm C., Porru, Stefano, Prescott, Jennifer, Prokunina-Olsson, Ludmila, Qian, Biyun, Qiao, You-Lin, Rais, Marco, Riboli, Elio, Riby, Jacques, Risch, Harvey A., Rizzato, Cosmeri, Rodabough, Rebecca, Roman, Eve, Roupret, Morgan, Ruder, Avima M., de Sanjose, Silvia, Scelo, Ghislaine, Schned, Alan, Schumacher, Fredrick, Schwartz, Kendra, Schwenn, Molly, Scotlandi, Katia, Seow, Adeline, Serra, Consol, Serra, Massimo, Sesso, Howard D., Setiawan, Veronica Wendy, Severi, Gianluca, Severson, Richard K., Shanafelt, Tait D., Shen, Hongbing, Shen, Wei, Shin, Min-Ho, Shiraishi, Kouya, Shu, Xiao-Ou, Siddiq, Afshan, Sierrasesúmaga, Luis, Sihoe, Alan Dart Loon, Skibola, Christine F., Smith, Alex, Smith, Martyn T., Southey, Melissa C., Spinelli, John J., Staines, Anthony, Stampfer, Meir, Stern, Marianna C., Stevens, Victoria L., Stolzenberg-Solomon, Rachael S., Su, Jian, Su, Wu-Chou, Sund, Malin, Sung, Jae Sook, Sung, Sook Whan, Tan, Wen, Tang, Wei, Tardón, Adonina, Thomas, David, Thompson, Carrie A., Tinker, Lesley F., Tirabosco, Roberto, Tjønneland, Anne, Travis, Ruth C., Trichopoulos, Dimitrios, Tsai, Fang-Yu, Tsai, Ying-Huang, Tucker, Margaret, Turner, Jenny, Vajdic, Claire M., Vermeulen, Roel C. H., Villano, Danylo J., Vineis, Paolo, Virtamo, Jarmo, Visvanathan, Kala, Wactawski-Wende, Jean, Wang, Chaoyu, Wang, Chih-Liang, Wang, Jiu-Cun, Wang, Junwen, Wei, Fusheng, Weiderpass, Elisabete, Weiner, George J., Weinstein, Stephanie, Wentzensen, Nicolas, White, Emily, Witzig, Thomas E., Wolpin, Brian M., Wong, Maria Pik, Wu, Chen, Wu, Guoping, Wu, Junjie, Wu, Tangchun, Wu, Wei, Wu, Xifeng, Wu, Yi-Long, Wunder, Jay S., Xiang, Yong-Bing, Xu, Jun, Xu, Ping, Yang, Pan-Chyr, Yang, Tsung-Ying, Ye, Yuanqing, Yin, Zhihua, Yokota, Jun, Yoon, Ho-Il, Yu, Chong-Jen, Yu, Herbert, Yu, Kai, Yuan, Jian-Min, Zelenetz, Andrew, Zeleniuch-Jacquotte, Anne, Zhang, Xu-Chao, Zhang, Yawei, Zhao, Xueying, Zhao, Zhenhong, Zheng, Hong, Zheng, Tongzhang, Zheng, Wei, Zhou, Baosen, Zhu, Meng, Zucca, Mariagrazia, Boca, Simina M., Cerhan, James R., Ferri, Giovanni M., Hartge, Patricia, Hsiung, Chao Agnes, Magnani, Corrado, Miligi, Lucia, Morton, Lindsay M., Smedby, Karin E., Teras, Lauren R., Vijai, Joseph, Wang, Sophia S., Brennan, Paul, Caporaso, Neil E., Hunter, David J., Kraft, Peter, Rothman, Nathaniel, Silverman, Debra T., Slager, Susan L., Chanock, Stephen J., and Chatterjee, Nilanjan
Subjects: Adult, Asian Continental Ancestry Group, Male, Lung Neoplasms, DATABASE, European Continental Ancestry Group, RELATIVES, Bone Neoplasms, Polymorphism, Single Nucleotide, Article, LUNG-CANCER, Testicular Neoplasms, Neoplasms, SWEDEN, LYMPHOMA, Humans, Genetic Predisposition to Disease, FAMILIAL RISK, Oncology & Carcinogenesis, Aged, Osteosarcoma, Science & Technology, MUTATIONS, Smoking, Middle Aged, Leukemia, Lymphocytic, Chronic, B-Cell, PANCREATIC-CANCER, Kidney Neoplasms, MULTIPLE SUSCEPTIBILITY LOCI, INDIVIDUALS, Oncology, Urinary Bladder Neoplasms, Tissue Array Analysis, Female, Lymphoma, Large B-Cell, Diffuse, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis, Genome-Wide Association Study
Abstract: Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common SNPs for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49,492 cancer cases and 34,131 controls. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl2, on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% CI = 14% - 37%) and 7% (4% - 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ=0.73, SE=0.28), Diffuse Large B-Cell Lymphoma (DLBCL) and pediatric osteosarcoma (ρ=0.53, SE=0.21), DLBCL and Chronic Lymphocytic Leukemia (CLL) (ρ=0.51, SE=0.18), and bladder and lung (ρ=0.35, SE=0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a non-smoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
Published: 2015

27. Acrylamide and glycidamide hemoglobin adduct levels and endometrial cancer risk: A nested case-control study in nonsmoking postmenopausal women from the EPIC cohort

Author: Obón-Santacana, Mireia, Freisling, Heinz, Peeters, Petra H., Lujan-Barroso, Leila, Ferrari, Pietro, Boutron-Ruault, Marie Christine, Mesrine, Sylvie, Baglietto, Laura, Turzanski-Fortner, Renee, Katzke, Verena A., Boeing, Heiner, Quirós, J. Ramón, Molina-Portillo, Elena, Larrañaga, Nerea, Chirlaque, María Dolores, Barricarte, Aurelio, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C., Merritt, Melissa A., Gunter, Marc J., Trichopoulou, Antonia, Lagiou, Pagona, Naska, Androniki, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Fiano, Valentina, Galassom, Rocco, Bueno-de-Mesquita, H. B., Onland-Moret, N. Charlotte, Idahl, Annika, Lundin, Eva, Weiderpass, Elisabete, Vesper, Hubert, Riboli, Elio, Duell, Eric J., and University Medical Center Utrecht
Subjects: Risk, Cancer Research, Glycidamide, BIOMARKERS, BREAST, Article, acrylamide, endometrial cancer, EPIC, glycidamide, hemoglobin adduct, Acrylamide, Biomarkers, Case-Control Studies, Endometrial Neoplasms, Epoxy Compounds, Female, Hemoglobins, Humans, Middle Aged, Postmenopause, Prospective Studies, Medicine (all), Oncology, Endometrial cancer, FOOD, Journal Article, Hemoglobin adduct, EXPOSURE, Oncology & Carcinogenesis, ASSOCIATIONS, Science & Technology, Research Support, Non-U.S. Gov't, OVARIAN, DIETARY ACRYLAMIDE, MODEL, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis
Abstract: Acrylamide, classified in 1994 by IARC as "probably carcinogenic to humans," was discovered in 2002 in some heat-treated, carbohydrate-rich foods. Four prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The purpose of this nested case-control study, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, was to evaluate, for the first time, the association between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) and the risk of developing EC in non-smoking postmenopausal women. Hemoglobin adducts were measured in red blood cells by HPLC/MS/MS. Four exposure variables were evaluated: HbAA, HbGA, their sum (HbAA+HbGA), and their ratio (HbGA/HbAA). The association between hemoglobin adducts and EC was evaluated using unconditional multivariable logistic regression models, and included 383 EC cases (171 were type-I EC), and 385 controls. Exposure variables were analyzed in quintiles based on control distributions. None of the biomarker variables had an effect on overall EC (HRHbAA;Q5vsQ1 : 0.84, 95%CI: 0.49-1.48; HRHbGA;Q5vsQ1 : 0.94, 95%CI: 0.54-1.63) or type-I EC risk. Additionally, none of the subgroups investigated (BMI 25 vs. ≥25 kg m(-2) , alcohol drinkers vs. never drinkers, oral contraceptive users vs. non-users) demonstrated effect measure modification. Hemoglobin adducts of acrylamide or glycidamide were not associated with EC or type-I EC risk in 768 nonsmoking postmenopausal women from the EPIC cohort.
Published: 2015

28. Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: results from the EPIC cohort

Author: Fortner, Renée T, Ose, Jennifer, Merritt, Melissa A., Schock, Helena, Tjønneland, Anne, Hansen, Louise, Overvad, Kim, Dossus, Laure, Clavel Chapelon, Françoise, Baglietto, Laura, Boeing, Heiner, Trichopoulou, Antonia, Benetou, Vassiliki, Lagiou, Pagona, Agnoli, Claudia, Mattiello, Amalia, Masala, Giovanna, Tumino, Rosario, Sacerdote, Carlotta, Bueno De Mesquita, H. B., Onland Moret, N. Charlotte, Peeters, Petra H., Weiderpass, Elisabete, Torhild Gram, Inger, Duell, Eric J, Larrañaga, Nerea, Ardanaz, Eva, Sánchez, María José, Chirlaque, M. D., Brändstedt, Jenny, Idahl, Annika, Lundin, Eva, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C., Rinaldi, Sabina, Romieu, Isabelle, Gunter, Marc J., Riboli, Elio, and Kaaks, Rudolf
Subjects: Adult, Cancer Research, endocrine system diseases, Term Birth, Carcinoma, Ovarian Epithelial, Article, Contraceptives, Oral, Hormonal, histologic subtype, dualistic model, AGE, ovarian cancer, reproductive factors, Medicine (all), Oncology, Pregnancy, Risk Factors, Humans, Neoplasms, Glandular and Epithelial, Prospective Studies, Oncology & Carcinogenesis, Aged, Ovarian Neoplasms, Science & Technology, ENDOMETRIAL CANCER, Middle Aged, female genital diseases and pregnancy complications, Europe, OBESITY, NUTRITION, Female, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis
Abstract: Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (phet=0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; phet=0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes. What's new? Reproductive and hormone-related risk factors for epithelial ovarian cancer (EOC) have been extensively investigated. However, EOC is increasingly recognized as a heterogeneous disease and risk factor differences across EOC subtypes, as defined by the recently proposed dualistic pathway of ovarian carcinogenesis and histological characteristics, are not well understood. Here, the authors present a detailed prospective investigation on reproductive and hormone-related risk factors for borderline tumors and epithelial ovarian cancer by main histological subtypes and, for the first time, by the types defined by the dualistic pathway. The results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.
Published: 2015

29. Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer

Author: Nimptsch, Katharina, Aleksandrova, Krasimira, Boeing, Heiner, Janke, Jürgen, Lee, Young-Ae, Jenab, Mazda, Yeon Kong, So, Tsilidis, Konstatinos K, Weiderpass, Elisabete, Bueno-De-Mesquita, Bas H, Siersema, Peter D, Jansen, Eugène H.J.M., Trichopoulou, Antonia, Tjønneland, Anne, Olsen, Anja, Wu, Chunsen, Overvad, Kim, Boutron-Ruault, Marie-Christine, Racine, Antoine, Freisling, Heinz, Katzke, Verena, Kaaks, Rudolf, Lagiou, Pagona, Trichopoulos, Dimitrios, Severi, Gianluca, Naccarati, Alessio, Mattiello, Amalia, Palli, Domenico, Grioni, Sara, Tumino, Rosario, Peeters, Petra H, Ljuslinder, Ingrid, Nyström, Hanna, Brändstedt, Jenny, Sánchez, María-José, Barricarte Gurrea, Aurelio, Bonet Bonet, Catalina, Chirlaque, María-Dolores, Dorronsoro, Miren, Quirós, José Ramón, Travis, Ruth C, Khaw, Kay-Tee, Wareham, Nick, Riboli, Elio, Gunter, Marc J, and Pischon, Tobias
Subjects: Male, Medicine(all), Cancer Research, alpha-2-HS-Glycoprotein, colorectal cancer, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Middle Aged, fetuin-A, Oncology, Cardiovascular and Metabolic Diseases, Risk Factors, AHSG, Case-Control Studies, Humans, Female, Colorectal Neoplasms, Aged
Abstract: Fetuin-A, also referred to as α2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 μg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 μg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development. What's new? Fetuin-A is a liver protein associated with insulin resistance, but with no defined role yet in colorectal cancer. In this prospective study, the authors uncover a modest linear association between fetuin-A levels and higher risk of colorectal cancer, but this was only observed in male participants. In addition, no association was observed between fetuin-A variants and colorectal cancer risk in a Mendelian randomization analysis, arguing against a direct role of fetuin-A in colorectal carcinogenesis.
Published: 2015

30. Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition

Author: Ose, Jennifer, Fortner, Renée T, Rinaldi, Sabina, Schock, Helena, Overvad, Kim, Tjonneland, Anne, Hansen, Louise, Dossus, Laure, Fournier, Agnes, Baglietto, Laura, Romieu, Isabelle, Kuhn, Elisabetta, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Palli, Domenico, Masala, Giovanna, Sieri, Sabina, Tumino, Rosario, Sacerdote, Carlotta, Mattiello, Amalia, Quiros, Jose Ramon, Obón-Santacana, Mireia, Larrañaga, Nerea, Chirlaque, María-Dolores, Sánchez, María-José, Barricarte, Aurelio, Peeters, Petra, Bueno-de-Mesquita, H Bas, Onland-Moret, Charlotte, Brändstedt, Jenny, Lundin, Eva, Idahl, Annika, Weiderpass, Elisabete, Gram, Inger T, Lund, Eiliv, Kaw, Kay-Tee, Travis, Ruth C, Merritt, Melissa, Gunther, Marc, Riboli, Elio, and Kaaks, Rudolf
Subjects: Adult, Cancer Research, endocrine system diseases, Nutritional Status, Carcinoma, Ovarian Epithelial, type 2 tumors, histologic subtype, type 1 tumors, Risk Factors, Sex Hormone-Binding Globulin, androstenedione, Fallopian Tube Neoplasms, Humans, Neoplasm Invasiveness, Neoplasms, Glandular and Epithelial, Prospective Studies, Peritoneal Neoplasms, Aged, Neoplasm Staging, Aged, 80 and over, Ovarian Neoplasms, Medicine(all), type I tumors, Medicine (all), endogenous androgens, ovarian carcinoma, type II tumors, Oncology, Middle Aged, Prognosis, female genital diseases and pregnancy complications, Cystadenocarcinoma, Serous, Europe, Case-Control Studies, Androgens, Female, Neoplasm Grading, Follow-Up Studies
Abstract: The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence interval [CI] = [0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 = 1.99 [0.98-4.06]; high grade: ORlog2 = 0.75 [0.61-0.93], phet ≤ 0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed. What's new? There appear to be several types of epithelial invasive ovarian cancer (EOC), and hormone-related risk factors are poorly understood. In this study, the authors found that the impact of endogenous androgens on the risk of developing EOC differed depending upon tumor characteristics. Androgen concentrations were positively associated with the risk of low-grade and type-I carcinomas, but the study found an inverse association for high-grade tumors. These findings support a possible role for androgens in ovarian carcinogenesis, and emphasize the need for additional research.
Published: 2015

31. Additive interactions between susceptibility single-nucleotide polymorphisms identified in genome-wide association studies and breast cancer risk factors in the Breast and Prostate Cancer Cohort Consortium

Author: Joshi, Amit D., Lindström, Sara, Hüsing, Anika, Barrdahl, Myrto, VanderWeele, Tyler J., Campa, Daniele, Canzian, Federico, Gaudet, Mia M., Figueroa, Jonine D., Baglietto, Laura, Berg, Christine D., Buring, Julie E., Chanock, Stephen J., Chirlaque, María-Dolores, Diver, W. Ryan, Dossus, Laure, Giles, Graham G., Haiman, Christopher A., Hankinson, Susan E., Henderson, Brian E., Hoover, Robert N., Hunter, David J., Isaacs, Claudine, Kaaks, Rudolf, Kolonel, Laurence N., Krogh, Vittorio, Le Marchand, Loic, Lee, I-Min, Lund, Eiliv, McCarty, Catherine A., Overvad, Kim, Peeters, Petra H., Riboli, Elio, Schumacher, Fredrick, Severi, Gianluca, Stram, Daniel O., Sund, Malin, Thun, Michael J., Travis, Ruth C., Trichopoulos, Dimitrios, Willett, Walter C., Zhang, Shumin, Ziegler, Regina G., Kraft, Peter, and Marchand, Loic Le
Subjects: Male, Oncology, medicine.medical_specialty, Pathology, Epidemiology, Original Contributions, Additive interactions, Breast cancer, Genome-wide association studies, Single-nucleotide polymorphisms, Breast Neoplasms, Single-nucleotide polymorphism, Genome-wide association study, Polymorphism, Single Nucleotide, Risk Assessment, White People, Body Mass Index, Cohort Studies, Prostate cancer, Risk Factors, Internal medicine, Biomarkers, Tumor, Odds Ratio, Humans, Medicine, Genetic Predisposition to Disease, Alleles, business.industry, Australia, Absolute risk reduction, Case-control study, Prostatic Neoplasms, Odds ratio, Middle Aged, medicine.disease, United States, DNA-Binding Proteins, Europe, Case-Control Studies, Female, Rad51 Recombinase, business, Risk assessment, Genome-Wide Association Study
Abstract: Additive interactions can have public health and etiological implications but are infrequently reported. We assessed departures from additivity on the absolute risk scale between 9 established breast cancer risk factors and 23 susceptibility single-nucleotide polymorphisms (SNPs) identified from genome-wide association studies among 10,146 non-Hispanic white breast cancer cases and 12,760 controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. We estimated the relative excess risk due to interaction and its 95% confidence interval for each pairwise combination of SNPs and nongenetic risk factors using age- and cohort-adjusted logistic regression models. After correction for multiple comparisons, we identified a statistically significant relative excess risk due to interaction (uncorrected P = 4.51 × 10(-5)) between a SNP in the DNA repair protein RAD51 homolog 2 gene (RAD51L1; rs10483813) and body mass index (weight (kg)/height (m)(2)). We also compared additive and multiplicative polygenic risk prediction models using per-allele odds ratio estimates from previous studies for breast-cancer susceptibility SNPs and observed that the multiplicative model had a substantially better goodness of fit than the additive model.
Published: 2014

32. Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and incidence of colorectal cancer

Author: Kyrø, Cecilie, Olsen, Anja, Landberg, Rikard, Skeie, Guri, Loft, Steffen, Åman, Per, Leenders, Max, Dik, Vincent K., Siersema, Peter D., Pischon, Tobias, Christensen, Jane, Overvad, Kim, Boutron-Ruault, Marie Christine, Fagherazzi, Guy, Cottet, Vanessa, Kühn, Tilman, Chang-Claude, Jenny, Boeing, Heiner, Trichopoulou, Antonia, Bamia, Christina, Trichopoulos, Dimitrios, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Peeters, Petra H., Weiderpass, Elisabete, Bakken, Toril, Åsli, Lene Angell, Argüelles, Marcial, Jakszyn, Paula, Sánchez, María José, Amiano, Pilar, Huerta, José María, Barricarte, Aurelio, Ljuslinder, Ingrid, Palmqvist, Richard, Khaw, Kay Tee, Wareham, Nick, Key, Timothy J., Travis, Ruth C., Ferrari, Pietro, Freisling, Heinz, Jenab, Mazda, Gunter, Marc J., Murphy, Neil, Riboli, Eilo, Tjønneland, Anne, Bueno-De-Mesquita, H. B., LS IRAS EEPI GRA (Gezh.risico-analyse), IRAS RATIA-SIB, Risk Assessment of Toxic and Immunomodulatory Agents, Kyr?, C, Olsen, A, Landberg, R, Skeie, G, Loft, S, Aman, P, Leenders, M, Dik, Vk, Siersema, Pd, Pischon, T, Christensen, J, Overvad, K, Boutron Ruault, Mc, Fagherazzi, G, Cottet, V, K?hn, T, Chang Claude, J, Boeing, H, Trichopoulou, A, Bamia, C, Trichopoulos, D, Palli, D, Krogh, V, Tumino, R, Vineis, P, Panico, Salvatore, Peeters, Ph, Weiderpass, E, Bakken, T, Asli, La, Arg?elles, M, Jakszyn, P, S?nchez, Mj, Amiano, P, Huerta, Jm, Barricarte, A, Ljuslinder, I, Palmqvist, R, Khaw, Kt, Wareham, N, Key, Tj, Travis, Rc, Ferrari, P, Freisling, H, Jenab, M, Gunter, Mj, Murphy, N, Riboli, E, Tj?nneland, A, Bueno de Mesquita, Hb, LS IRAS EEPI GRA (Gezh.risico-analyse), IRAS RATIA-SIB, and Risk Assessment of Toxic and Immunomodulatory Agents
Subjects: Male, medicine.medical_specialty, Pathology, Cancer Research, Colorectal cancer, Scandinavian and Nordic Countries, Rate ratio, Gastroenterology, Body Mass Index, Alkylresorcinol, Risk Factors, Internal medicine, Odds Ratio, Medicine, Humans, Triticum, Aged, Cancer och onkologi, business.industry, Mediterranean Region, Incidence (epidemiology), Incidence, Secale, Case-control study, food and beverages, Cancer, Odds ratio, Feeding Behavior, Resorcinols, Middle Aged, medicine.disease, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Logistic Models, Oncology, Cardiovascular and Metabolic Diseases, Cancer and Oncology, Case-Control Studies, Female, business, Colorectal Neoplasms, Biomarkers
Abstract: Background Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations. Methods The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional differences (Scandinavia, the Mediterranean, Central Europe) were also explored. Results High plasma total alkylresorcinol concentration was associated with lower incidence of distal colon cancer; the adjusted incidence rate ratio of distal colon cancer for the highest vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence interval [CI] = 0.28 to 0.83). An inverse association between plasma total alkylresorcinol concentrations and colon cancer was found for Scandinavian participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma total alkylresorcinol concentrations were not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher). Conclusions High concentrations of plasma alkylresorcinols were associated with a lower incidence of distal colon cancer but not with overall colorectal cancer, proximal colon cancer, and rectal cancer.
Published: 2013

33. Physical activity and risk of Amyotrophic Lateral Sclerosis in a prospective cohort study

Author: Gallo, Valentina, Vanacore, Nicola, Bueno-de-Mesquita, H Bas, Vermeulen, Roel, Brayne, Carol, Pearce, Neil, Wark, Petra A, Ward, Heather A, Ferrari, Pietro, Jenab, Mazda, Andersen, Peter M, Wennberg, Patrik, Wareham, Nicholas, Katzke, Verena, Kaaks, Rudolf, Weiderpass, Elisabete, Peeters, Petra H, Mattiello, Amalia, Pala, Valeria, Barricante, Aurelio, Chirlaque, Maria-Dolores, Travier, Noémie, Travis, Ruth C, Sanchez, Maria-Jose, Pessah-Rasmussen, Hélène, Petersson, Jesper, Tjønneland, Anne, Tumino, Rosario, Quiros, Jose Ramon, Trichopoulou, Antonia, Kyrozis, Andreas, Oikonomidou, Despoina, Masala, Giovanna, Sacerdote, Carlotta, Arriola, Larraitz, Boeing, Heiner, Vigl, Matthaeus, Claver-Chapelon, Francoise, Middleton, Lefkos, Riboli, Elio, Vineis, Paolo, LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-I&I RA, dIRAS RA-2, LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-I&I RA, dIRAS RA-2, Department of Medical and Clinical Genetics, Medicum, University Medical Center Utrecht, and Imperial College Trust
Subjects: Gerontology, Male, Epidemiology, VDP::Medisinske Fag: 700::Helsefag: 800::Epidemiologi medisinsk og odontologisk statistikk: 803, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Nevrologi: 752, Body Mass Index, EPIC COHORT, 0302 clinical medicine, Risk Factors, Surveys and Questionnaires, Medicine, MOTOR-NEURON DISEASE, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Non-U.S. Gov't, Vigorous physical activity, POPULATION, Public, Environmental & Occupational Health, education.field_of_study, Anthropometry, Research Support, Non-U.S. Gov't, DEATH, Age Factors, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, Neuro-Epidemiology, CANCER, 3142 Public health care science, environmental and occupational health, 3. Good health, European Prospective Investigation into Cancer and Nutrition, VDP::Medical disciplines: 700::Health sciences: 800::Epidemiology medical and dental statistics: 803, Female, Cohort study, Life Sciences & Biomedicine, Neurovetenskaper, Adult, medicine.medical_specialty, Population, Public Health And Health Services, Motor Activity, Research Support, 03 medical and health sciences, BMI, Internal medicine, Journal Article, Humans, VALIDITY, PLAYERS, education, Aged, Proportional Hazards Models, Science & Technology, business.industry, Proportional hazards model, BLOOD-BRAIN-BARRIER, Physical activity, Amyotrophic Lateral Sclerosis, Neurosciences, BODY-MASS, EPIC study, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Socioeconomic Factors, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Neurology: 752, ALS, business, Body mass index, 030217 neurology & neurosurgery
Abstract: Previous case–control studies have suggested a possible increased risk of Amyotrophic Lateral Sclerosis (ALS) with physical activity (PA), but this association has never been studied in prospective cohort studies. We therefore assessed the association between PA and risk of death from ALS in the European Prospective Investigation into Cancer and Nutrition. A total of 472,100 individuals were included in the analysis, yielding 219 ALS deaths. At recruitment, information on PA was collected thorough standardised questionnaires. Total PA was expressed by the Cambridge Physical Activity Index (CPAI) and analysed in relation to ALS mortality, using Cox hazard models. Interactions with age, sex, and anthropometric measures were assessed. Total PA was weakly inversely associated with ALS mortality with a borderline statistically significant trend across categories (p = 0.042), with those physically active being 33 % less likely to die from ALS compared to those inactive: HR = 0.67 (95 % CI 0.42–1.06). Anthropometric measures, sex, and age did not modify the association with CPAI. The present study shows a slightly decreased—not increased like in case–control studies—risk of dying from ALS in those with high levels of total PA at enrolment. This association does not appear confounded by age, gender, anthropometry, smoking, and education. Ours was the first prospective cohort study on ALS and physical activity. Electronic supplementary material The online version of this article (doi:10.1007/s10654-016-0119-9) contains supplementary material, which is available to authorized users.
Published: 2016

34. Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort

Author: Dossus, Laure, Boutron-Ruault, Marie-Christine, Kaaks, Rudolf, Gram, Inger T, Vilier, Alice, Fervers, Béatrice, Manjer, Jonas, Tjonneland, Anne, Olsen, Anja Viendahl, Overvad, Kim, Chang-Claude, Jenny, Boeing, Heiner, Steffen, Annika, Trichopoulou, Antonia, Lagiou, Pagona, Sarantopoulou, Maria, Palli, Domenico, Berrino, Franco, Tumino, Rosario, Vineis, Paolo, Mattiello, Amalia, Bueno-de-Mesquita, H Bas, van Duijnhoven, Franzel J B, Bakker, Marieke F, Peeters, Petra Hm, Weiderpass, Elisabete, Bjerkaas, Eivind, Braaten, Tonje, Menéndez, Virginia, Agudo, Antonio, Sanchez, Maria-Jose, Amiano, Pilar, Tormo, Maria-Jose, Barricarte, Aurelio, Butt, Salma, Khaw, Kay-Tee, Wareham, Nicholas, Key, Tim J, Travis, Ruth C, Rinaldi, Sabina, McCormack, Valerie, Romieu, Isabelle, Cox, David G, Norat, Teresa, Riboli, Elio, and Clavel-Chapelon, Françoise
Subjects: Cohort Studies, Risk, Dose-Response Relationship, Drug, Risk Factors, Incidence, Surveys and Questionnaires, Smoking, Humans, Breast Neoplasms, Female, Tobacco Smoke Pollution, Prospective Studies
Abstract: Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05-1.28], 1.14 [1.04-1.25] and 1.10 [1.01-1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29-2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34-0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious.
Published: 2012

35. Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis

Author: Papadimitriou, Nikos, Dimou, Niki, Tsilidis, Konstantinos K, Banbury, Barbara, Martin, Richard M, Lewis, Sarah J, Kazmi, Nabila, Robinson, Timothy M, Albanes, Demetrius, Aleksandrova, Krasimira, Berndt, Sonja I, Timothy Bishop, D, Brenner, Hermann, Buchanan, Daniel D, Bueno-De-Mesquita, Bas, Campbell, Peter T, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, Ellingjord-Dale, Merete, Figueiredo, Jane C, Gallinger, Steven J, Giles, Graham G, Giovannucci, Edward, Gruber, Stephen B, Gsur, Andrea, Hampe, Jochen, Hampel, Heather, Harlid, Sophia, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hsu, Li, María Huerta, José, Huyghe, Jeroen R, Jenkins, Mark A, Keku, Temitope O, Kühn, Tilman, La Vecchia, Carlo, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane M, Lynch, Brigid, Markowitz, Sanford D, Masala, Giovanna, May, Anne M, Milne, Roger, Monninkhof, Evelyn, Moreno, Lorena, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Perduca, Vittorio, Pharoah, Paul DP, Platz, Elizabeth A, Potter, John D, Rennert, Gad, Riboli, Elio, Sánchez, Maria-Jose, Schmit, Stephanie L, Schoen, Robert E, Severi, Gianluca, Sieri, Sabina, Slattery, Martha L, Song, Mingyang, Tangen, Catherine M, Thibodeau, Stephen N, Travis, Ruth C, Trichopoulou, Antonia, Ulrich, Cornelia M, Van Duijnhoven, Franzel JB, Van Guelpen, Bethany, Vodicka, Pavel, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Peters, Ulrike, Gunter, Marc J, and Murphy, Neil
Subjects: Risk Factors, Accelerometry, Odds Ratio, Humans, Breast Neoplasms, Female, Genetic Predisposition to Disease, Mendelian Randomization Analysis, Colorectal Neoplasms, Exercise, Polymorphism, Single Nucleotide, 3. Good health
Abstract: Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.

36. A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Murphy, Neil, Cross, Amanda J, Abubakar, Mustapha, Jenab, Mazda, Aleksandrova, Krasimira, Boutron-Ruault, Marie-Christine, Dossus, Laure, Racine, Antoine, Kühn, Tilman, Katzke, Verena A, Tjønneland, Anne, Petersen, Kristina EN, Overvad, Kim, Quirós, J Ramón, Jakszyn, Paula, Molina-Montes, Esther, Dorronsoro, Miren, Huerta, José-María, Barricarte, Aurelio, Khaw, Kay-Tee, Wareham, Nick, Travis, Ruth C, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Masala, Giovanna, Krogh, Vittorio, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno-De-Mesquita, H Bas, Siersema, Peter D, Peeters, Petra H, Ohlsson, Bodil, Ericson, Ulrika, Palmqvist, Richard, Nyström, Hanna, Weiderpass, Elisabete, Skeie, Guri, Freisling, Heinz, Kong, So Yeon, Tsilidis, Kostas, Muller, David C, Riboli, Elio, and Gunter, Marc J
Subjects: Male, Health Status, Risk Assessment, Body Mass Index, Risk Factors, Hyperinsulinism, Odds Ratio, Body Size, Humans, Obesity, Prospective Studies, Adiposity, 2. Zero hunger, Obesity, Metabolically Benign, Chi-Square Distribution, C-Peptide, Incidence, nutritional and metabolic diseases, Middle Aged, Protective Factors, 3. Good health, Europe, Logistic Models, Phenotype, Case-Control Studies, Multivariate Analysis, Female, Waist Circumference, Colorectal Neoplasms, Biomarkers
Abstract: BACKGROUND: Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. METHODS AND FINDINGS: The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of

37. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

Author: Southey, Melissa C, Goldgar, David E, Winqvist, Robert, Pylkäs, Katri, Couch, Fergus, Tischkowitz, Marc, Foulkes, William D, Dennis, Joe, Michailidou, Kyriaki, Van Rensburg, Elizabeth J, Heikkinen, Tuomas, Nevanlinna, Heli, Hopper, John L, Dörk, Thilo, Claes, Kathleen Bm, Reis-Filho, Jorge, Teo, Zhi Ling, Radice, Paolo, Catucci, Irene, Peterlongo, Paolo, Tsimiklis, Helen, Odefrey, Fabrice A, Dowty, James G, Schmidt, Marjanka K, Broeks, Annegien, Hogervorst, Frans B, Verhoef, Senno, Carpenter, Jane, Clarke, Christine, Scott, Rodney J, Fasching, Peter A, Haeberle, Lothar, Ekici, Arif B, Beckmann, Matthias W, Peto, Julian, Dos-Santos-Silva, Isabel, Fletcher, Olivia, Johnson, Nichola, Bolla, Manjeet K, Sawyer, Elinor J, Tomlinson, Ian, Kerin, Michael J, Miller, Nicola, Marme, Federik, Burwinkel, Barbara, Yang, Rongxi, Guénel, Pascal, Truong, Thérèse, Menegaux, Florence, Sanchez, Marie, Bojesen, Stig, Nielsen, Sune F, Flyger, Henrik, Benitez, Javier, Zamora, M Pilar, Perez, Jose Ignacio Arias, Menéndez, Primitiva, Anton-Culver, Hoda, Neuhausen, Susan, Ziogas, Argyrios, Clarke, Christina A, Brenner, Hermann, Arndt, Volker, Stegmaier, Christa, Brauch, Hiltrud, Brüning, Thomas, Ko, Yon-Dschun, Muranen, Taru A, Aittomäki, Kristiina, Blomqvist, Carl, Bogdanova, Natalia V, Antonenkova, Natalia N, Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M, Spurdle, Amanda B, Investigators, KConFab, Australian Ovarian Cancer Study Group, Wauters, Els, Smeets, Dominiek, Beuselinck, Benoit, Floris, Giuseppe, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Olson, Janet E, Vachon, Celine, Pankratz, Vernon S, McLean, Catriona, Haiman, Christopher A, Henderson, Brian E, Schumacher, Fredrick, Le Marchand, Loic, Kristensen, Vessela, Alnæs, Grethe Grenaker, Zheng, Wei, Hunter, David J, Lindstrom, Sara, Hankinson, Susan E, Kraft, Peter, Andrulis, Irene, Knight, Julia A, Glendon, Gord, Mulligan, Anna Marie, Jukkola-Vuorinen, Arja, Grip, Mervi, Kauppila, Saila, Devilee, Peter, Tollenaar, Robert AEM, Seynaeve, Caroline, Hollestelle, Antoinette, Garcia-Closas, Montserrat, Figueroa, Jonine, Chanock, Stephen J, Lissowska, Jolanta, Czene, Kamila, Darabi, Hatef, Eriksson, Mikael, Eccles, Diana M, Rafiq, Sajjad, Tapper, William J, Gerty, Sue M, Hooning, Maartje J, Martens, John WM, Collée, J Margriet, Tilanus-Linthorst, Madeleine, Hall, Per, Li, Jingmei, Brand, Judith S, Humphreys, Keith, Cox, Angela, Reed, Malcolm WR, Luccarini, Craig, Baynes, Caroline, Dunning, Alison M, Hamann, Ute, Torres, Diana, Ulmer, Hans Ulrich, Rüdiger, Thomas, Jakubowska, Anna, Lubinski, Jan, Jaworska, Katarzyna, Durda, Katarzyna, Slager, Susan, Toland, Amanda E, Ambrosone, Christine B, Yannoukakos, Drakoulis, Swerdlow, Anthony, Ashworth, Alan, Orr, Nick, Jones, Michael, González-Neira, Anna, Pita, Guillermo, Alonso, M Rosario, Álvarez, Nuria, Herrero, Daniel, Tessier, Daniel C, Vincent, Daniel, Bacot, Francois, Simard, Jacques, Dumont, Martine, Soucy, Penny, Eeles, Rosalind, Muir, Kenneth, Wiklund, Fredrik, Gronberg, Henrik, Schleutker, Johanna, Nordestgaard, Børge G, Weischer, Maren, Travis, Ruth C, Neal, David, Donovan, Jenny L, Hamdy, Freddie C, Khaw, Kay-Tee, Stanford, Janet L, Blot, William J, Thibodeau, Stephen, Schaid, Daniel J, Kelley, Joseph L, Maier, Christiane, Kibel, Adam S, Cybulski, Cezary, Cannon-Albright, Lisa, Butterbach, Katja, Park, Jong, Kaneva, Radka, Batra, Jyotsna, Teixeira, Manuel R, Kote-Jarai, Zsofia, Olama, Ali Amin Al, Benlloch, Sara, Renner, Stefan P, Hartmann, Arndt, Hein, Alexander, Ruebner, Matthias, Lambrechts, Diether, Van Nieuwenhuysen, Els, Vergote, Ignace, Lambretchs, Sandrina, Doherty, Jennifer A, Rossing, Mary Anne, Nickels, Stefan, Eilber, Ursula, Wang-Gohrke, Shan, Odunsi, Kunle, Sucheston-Campbell, Lara E, Friel, Grace, Lurie, Galina, Killeen, Jeffrey L, Wilkens, Lynne R, Goodman, Marc T, Runnebaum, Ingo, Hillemanns, Peter A, Pelttari, Liisa M, Butzow, Ralf, Modugno, Francesmary, Edwards, Robert P, Ness, Roberta B, Moysich, Kirsten B, Du Bois, Andreas, Heitz, Florian, Harter, Philipp, Kommoss, Stefan, Karlan, Beth Y, Walsh, Christine, Lester, Jenny, Jensen, Allan, Kjaer, Susanne Krüger, Høgdall, Estrid, Peissel, Bernard, Bonanni, Bernardo, Bernard, Loris, Goode, Ellen L, Fridley, Brooke L, Vierkant, Robert A, Cunningham, Julie M, Larson, Melissa C, Fogarty, Zachary C, Kalli, Kimberly R, Liang, Dong, Lu, Karen H, Hildebrandt, Michelle AT, Wu, Xifeng, Levine, Douglas A, Dao, Fanny, Bisogna, Maria, Berchuck, Andrew, Iversen, Edwin S, Marks, Jeffrey R, Akushevich, Lucy, Cramer, Daniel W, Schildkraut, Joellen, Terry, Kathryn L, Poole, Elizabeth M, Stampfer, Meir, Tworoger, Shelley S, Bandera, Elisa V, Orlow, Irene, Olson, Sara H, Bjorge, Line, Salvesen, Helga B, Van Altena, Anne M, Aben, Katja KH, Kiemeney, Lambertus A, Massuger, Leon FAG, Pejovic, Tanja, Bean, Yukie, Brooks-Wilson, Angela, Kelemen, Linda E, Cook, Linda S, Le, Nhu D, Górski, Bohdan, Gronwald, Jacek, Menkiszak, Janusz, Høgdall, Claus K, Lundvall, Lene, Nedergaard, Lotte, Engelholm, Svend Aage, Dicks, Ed, Tyrer, Jonathan, Campbell, Ian, McNeish, Iain, Paul, James, Siddiqui, Nadeem, Glasspool, Rosalind, Whittemore, Alice S, Rothstein, Joseph H, McGuire, Valerie, Sieh, Weiva, Cai, Hui, Shu, Xiao-Ou, Teten, Rachel T, Sutphen, Rebecca, McLaughlin, John R, Narod, Steven A, Phelan, Catherine M, Monteiro, Alvaro N, Fenstermacher, David, Lin, Hui-Yi, Permuth, Jennifer B, Sellers, Thomas A, Chen, Y Ann, Tsai, Ya-Yu, Chen, Zhihua, Gentry-Maharaj, Aleksandra, Gayther, Simon A, Ramus, Susan J, Menon, Usha, Wu, Anna H, Pearce, Celeste L, Van Den Berg, David, Pike, Malcolm C, Dansonka-Mieszkowska, Agnieszka, Plisiecka-Halasa, Joanna, Moes-Sosnowska, Joanna, Kupryjanczyk, Jolanta, Pharoah, Paul Dp, Song, Honglin, Winship, Ingrid, Chenevix-Trench, Georgia, Giles, Graham G, Tavtigian, Sean V, Easton, Doug F, and Milne, Roger L
Subjects: Male, Ovarian Neoplasms, Risk, Cancer: breast, Tumor Suppressor Proteins, cancer predisposition, Nuclear Proteins, Prostatic Neoplasms, Breast Neoplasms, Ataxia Telangiectasia Mutated Proteins, 3. Good health, Cancer: prostate, Cancer: ovary, Checkpoint Kinase 2, FOS: Biological sciences, Case-Control Studies, Mutation, Genetics, Humans, Female, Genetic Predisposition to Disease, Fanconi Anemia Complementation Group N Protein, Genetic Association Studies
Abstract: BACKGROUND: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. METHODS: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. RESULTS: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10-5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10-8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. CONCLUSIONS: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.

38. Prediction of acute myeloid leukaemia risk in healthy individuals

Author: Abelson, Sagi, Collord, Grace, Ng, Stanley WK, Weissbrod, Omer, Mendelson Cohen, Netta, Niemeyer, Elisabeth, Barda, Noam, Zuzarte, Philip C, Heisler, Lawrence, Sundaravadanam, Yogi, Luben, Robert, Hayat, Shabina, Wang, Ting Ting, Zhao, Zhen, Cirlan, Iulia, Pugh, Trevor J, Soave, David, Ng, Karen, Latimer, Calli, Hardy, Claire, Raine, Keiran, Jones, David, Hoult, Diana, Britten, Abigail, McPherson, John D, Johansson, Mattias, Mbabaali, Faridah, Eagles, Jenna, Miller, Jessica K, Pasternack, Danielle, Timms, Lee, Krzyzanowski, Paul, Awadalla, Philip, Costa, Rui, Segal, Eran, Bratman, Scott V, Beer, Philip, Behjati, Sam, Martincorena, Inigo, Wang, Jean CY, Bowles, Kristian M, Quirós, J Ramón, Karakatsani, Anna, La Vecchia, Carlo, Trichopoulou, Antonia, Salamanca-Fernández, Elena, Huerta, José M, Barricarte, Aurelio, Travis, Ruth C, Tumino, Rosario, Masala, Giovanna, Boeing, Heiner, Panico, Salvatore, Kaaks, Rudolf, Krämer, Alwin, Sieri, Sabina, Riboli, Elio, Vineis, Paolo, Foll, Matthieu, McKay, James, Polidoro, Silvia, Sala, Núria, Khaw, Kay-Tee, Vermeulen, Roel, Campbell, Peter J, Papaemmanuil, Elli, Minden, Mark D, Tanay, Amos, Balicer, Ran D, Wareham, Nicholas J, Gerstung, Moritz, Dick, John E, Brennan, Paul, Vassiliou, George S, and Shlush, Liran I
Subjects: Adult, Male, Models, Genetic, Age Factors, Middle Aged, Risk Assessment, 3. Good health, Leukemia, Myeloid, Acute, Health, Mutagenesis, hemic and lymphatic diseases, Mutation, Disease Progression, Prevalence, Electronic Health Records, Humans, Female, Genetic Predisposition to Disease, neoplasms, Aged
Abstract: The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure1. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion2,3. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)4-8. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.

39. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Kar, Siddhartha P, Beesley, Jonathan, Amin Al Olama, Ali, Michailidou, Kyriaki, Tyrer, Jonathan, Kote-Jarai, ZSofia, Lawrenson, Kate, Lindstrom, Sara, Ramus, Susan J, Thompson, Deborah J, ABCTB Investigators, Kibel, Adam S, Dansonka-Mieszkowska, Agnieszka, Michael, Agnieszka, Dieffenbach, Aida K, Gentry-Maharaj, Aleksandra, Whittemore, Alice S, Wolk, Alicja, Monteiro, Alvaro, Peixoto, Ana, Kierzek, Andrzej, Cox, Angela, Rudolph, Anja, Gonzalez-Neira, Anna, Wu, Anna H, Lindblom, Annika, Swerdlow, Anthony, AOCS Study Group & Australian Cancer Study (Ovarian Cancer), APCB BioResource, Ziogas, Argyrios, Ekici, Arif B, Burwinkel, Barbara, Karlan, Beth Y, Nordestgaard, Børge G, Blomqvist, Carl, Phelan, Catherine, McLean, Catriona, Pearce, Celeste Leigh, Vachon, Celine, Cybulski, Cezary, Slavov, Chavdar, Stegmaier, Christa, Maier, Christiane, Ambrosone, Christine B, Høgdall, Claus K, Teerlink, Craig C, Kang, Daehee, Tessier, Daniel C, Schaid, Daniel J, Stram, Daniel O, Cramer, Daniel W, Neal, David E, Eccles, Diana, Flesch-Janys, Dieter, Edwards, Digna R Velez, Wokozorczyk, Dominika, Levine, Douglas A, Yannoukakos, Drakoulis, Sawyer, Elinor J, Bandera, Elisa V, Poole, Elizabeth M, Goode, Ellen L, Khusnutdinova, Elza, Høgdall, Estrid, Song, Fengju, Bruinsma, Fiona, Heitz, Florian, Modugno, Francesmary, Hamdy, Freddie C, Wiklund, Fredrik, Giles, Graham G, Olsson, Håkan, Wildiers, Hans, Ulmer, Hans-Ulrich, Pandha, Hardev, Risch, Harvey A, Darabi, Hatef, Salvesen, Helga B, Nevanlinna, Heli, Gronberg, Henrik, Brenner, Hermann, Brauch, Hiltrud, Anton-Culver, Hoda, Song, Honglin, Lim, Hui-Yi, McNeish, Iain, Campbell, Ian, Vergote, Ignace, Gronwald, Jacek, Lubiński, Jan, Stanford, Janet L, Benítez, Javier, Doherty, Jennifer A, Permuth, Jennifer B, Chang-Claude, Jenny, Donovan, Jenny L, Dennis, Joe, Schildkraut, Joellen M, Schleutker, Johanna, Hopper, John L, Kupryjanczyk, Jolanta, Park, Jong Y, Figueroa, Jonine, Clements, Judith A, Knight, Julia A, Peto, Julian, Cunningham, Julie M, Pow-Sang, Julio, Batra, Jyotsna, Czene, Kamila, Lu, Karen H, Herkommer, Kathleen, Khaw, Kay-Tee, KConFab Investigators, Matsuo, Keitaro, Muir, Kenneth, Offitt, Kenneth, Chen, Kexin, Moysich, Kirsten B, Aittomäki, Kristiina, Odunsi, Kunle, Kiemeney, Lambertus A, Massuger, Leon FAG, Fitzgerald, Liesel M, Cook, Linda S, Cannon-Albright, Lisa, Hooning, Maartje J, Pike, Malcolm C, Bolla, Manjeet K, Luedeke, Manuel, Teixeira, Manuel R, Goodman, Marc T, Schmidt, Marjanka K, Riggan, Marjorie, Aly, Markus, Rossing, Mary Anne, Beckmann, Matthias W, Moisse, Matthieu, Sanderson, Maureen, Southey, Melissa C, Jones, Michael, Lush, Michael, Hildebrandt, Michelle AT, Hou, Ming-Feng, Schoemaker, Minouk J, Garcia-Closas, Montserrat, Bogdanova, Natalia, Rahman, Nazneen, NBCS Investigators, Le, Nhu D, Orr, Nick, Wentzensen, Nicolas, Pashayan, Nora, Peterlongo, Paolo, Guénel, Pascal, Brennan, Paul, Paulo, Paula, Webb, Penelope M, Broberg, Per, Fasching, Peter A, Devilee, Peter, Wang, Qin, Cai, Qiuyin, Li, Qiyuan, Kaneva, Radka, Butzow, Ralf, Kopperud, Reidun Kristin, Schmutzler, Rita K, Stephenson, Robert A, MacInnis, Robert J, Hoover, Robert N, Winqvist, Robert, Ness, Roberta, Milne, Roger L, Travis, Ruth C, Benlloch, Sara, Olson, Sara H, McDonnell, Shannon K, Tworoger, Shelley S, Maia, Sofia, Berndt, Sonja, Lee, Soo Chin, Teo, Soo-Hwang, Thibodeau, Stephen N, Bojesen, Stig E, Gapstur, Susan M, Kjær, Susanne Krüger, Pejovic, Tanja, Tammela, Teuvo LJ, GENICA Network, PRACTICAL Consortium, Dörk, Thilo, Brüning, Thomas, Wahlfors, Tiina, Key, Tim J, Edwards, Todd L, Menon, Usha, Hamann, Ute, Mitev, Vanio, Kosma, Veli-Matti, Setiawan, Veronica Wendy, Kristensen, Vessela, Arndt, Volker, Vogel, Walther, Zheng, Wei, Sieh, Weiva, Blot, William J, Kluzniak, Wojciech, Shu, Xiao-Ou, Gao, Yu-Tang, Schumacher, Fredrick, Freedman, Matthew L, Berchuck, Andrew, Dunning, Alison M, Simard, Jacques, Haiman, Christopher A, Spurdle, Amanda, Sellers, Thomas A, Hunter, David J, Henderson, Brian E, Kraft, Peter, Chanock, Stephen J, Couch, Fergus J, Hall, Per, Gayther, Simon A, Easton, Douglas F, Chenevix-Trench, Georgia, Eeles, Rosalind, Pharoah, Paul DP, and Lambrechts, Diether
Subjects: Male, Ovarian Neoplasms, Quantitative Trait Loci, Chromosome Mapping, Datasets as Topic, Prostatic Neoplasms, Breast Neoplasms, Polymorphism, Single Nucleotide, 3. Good health, Enhancer Elements, Genetic, Meta-Analysis as Topic, Genetic Loci, Organ Specificity, Case-Control Studies, Humans, Female, Gene Regulatory Networks, Genetic Predisposition to Disease, Genome-Wide Association Study, Signal Transduction
Abstract: UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

40. Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans

Author: Stepien, Magdalena, Hughes, David J, Hybsier, Sandra, Bamia, Christina, Tjønneland, Anne, Overvad, Kim, Affret, Aurélie, His, Mathilde, Boutron-Ruault, Marie-Christine, Katzke, Verena, Kühn, Tilman, Aleksandrova, Krasimira, Trichopoulou, Antonia, Lagiou, Pagona, Orfanos, Phlippos, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Bueno-De-Mesquita, HB As, Peeters, Petra H, Weiderpass, Elisabete, Lasheras, Cristina, Bonet Bonet, Catalina, Molina-Portillo, Elena, Dorronsoro, Miren, Huerta, José María, Barricarte, Aurelio, Ohlsson, Bodil, Sjöberg, Klas, Werner, Mårten, Shungin, Dmitry, Wareham, Nick, Khaw, Kay-Tee, Travis, Ruth C, Freisling, Heinz, Cross, Amanda J, Schomburg, Lutz, and Jenab, Mazda
Subjects: Male, Carcinoma, Hepatocellular, Liver Neoplasms, Middle Aged, 3. Good health, Europe, Zinc, Biliary Tract Neoplasms, Case-Control Studies, Humans, Female, Prospective Studies, Copper, Aged
Abstract: BACKGROUND: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers. METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk. RESULTS: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, Ptrend=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, Ptrend=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, Ptrend=0.0135). For IHBC and GBTC, no significant associations were observed. CONCLUSIONS: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.

41. Shared heritability and functional enrichment across six solid cancers

Author: Jiang, Xia, Finucane, Hilary K, Schumacher, Fredrick R, Schmit, Stephanie L, Tyrer, Jonathan P, Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B, Dennis, Joe, Conti, David V, Casey, Graham, Gaudet, Mia M, Huyghe, Jeroen R, Albanes, Demetrius, Aldrich, Melinda C, Andrew, Angeline S, Andrulis, Irene L, Anton-Culver, Hoda, Antoniou, Antonis C, Antonenkova, Natalia N, Arnold, Susanne M, Aronson, Kristan J, Arun, Banu K, Bandera, Elisa V, Barkardottir, Rosa B, Barnes, Daniel R, Batra, Jyotsna, Beckmann, Matthias W, Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I, Bickeböller, Heike, Bien, Stephanie A, Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Brauch, Hiltrud, Brenner, Hermann, Brenton, James D, Brook, Mark N, Brunet, Joan, Brunnström, Hans, Buchanan, Daniel D, Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Campbell, Peter T, Cancel-Tassin, Géraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, André L, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Chu, Christiani, David C, Claes, Kathleen BM, Claessens, Frank, Clements, Judith, Collée, J Margriet, Correa, Marcia Cruz, Couch, Fergus J, Cox, Angela, Cunningham, Julie M, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, DeFazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L, Dörk, Thilo, Duell, Eric J, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Edlund, Christopher K, Edwards, Digna R Velez, Ellberg, Carolina, Evans, D Gareth, Fasching, Peter A, Ferris, Robert L, Liloglou, Triantafillos, Figueiredo, Jane C, Fletcher, Olivia, Fortner, Renée T, Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J, Ganz, Patricia A, Garber, Judy, García-Sáenz, José A, Gayther, Simon A, Giles, Graham G, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, Goode, Ellen L, Goodman, Marc T, Goodman, Gary, Grankvist, Kjell, Greene, Mark H, Gronberg, Henrik, Gronwald, Jacek, Guénel, Pascal, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C, Hamilton, Robert J, Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Høgdall, Estrid, Hong, Yun-Chul, Hopper, John L, Houlston, Richard, Hulick, Peter J, Hunter, David J, Huntsman, David G, Idos, Gregory, Imyanitov, Evgeny N, Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A, Johansson, Mattias, Johansson, Mikael, John, Esther M, Joshi, Amit D, Kaneva, Radka, Karlan, Beth Y, Kelemen, Linda E, Kühl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S, Kiemeney, Lambertus A, Kim, Jeri, Kjaer, Susanne K, Knight, Julia A, Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N, Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D, Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A, Li, Li, Li, Christopher I, Lindblom, Annika, Lindor, Noralane M, Liu, Geoffrey, Loupakis, Fotios, Lubiński, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Marchand, Loic Le, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L, MacInnis, Robert J, Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B, Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L, Neal, David E, Ness, Andrew R, Neuhausen, Susan L, Nevanlinna, Heli, Newcomb, Polly A, Newcomb, Lisa F, Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Børge G, Nussbaum, Robert L, Offit, Kenneth, Olah, Edith, Olama, Ali Amin Al, Olopade, Olufunmilayo I, Olshan, Andrew F, Olsson, Håkan, Osorio, Ana, Pandha, Hardev, Park, Jong Y, Pashayan, Nora, Parsons, Michael T, Pejovic, Tanja, Penney, Kathryn L, Peters, Wilbert HM, Phelan, Catherine M, Phipps, Amanda I, Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J, Raskin, Leon, Rennert, Gad, Rennert, Hedy S, Van Rensburg, Elizabeth J, Riggan, Marjorie J, Risch, Harvey A, Risch, Angela, Roobol, Monique J, Rosenstein, Barry S, Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P, Sawyer, Elinor J, Schabath, Matthew B, Schleutker, Johanna, Schmidt, Marjanka K, Setiawan, V Wendy, Shen, Hongbing, Siegel, Erin M, Sieh, Weiva, Singer, Christian F, Slattery, Martha L, Sorensen, Karina Dalsgaard, Southey, Melissa C, Spurdle, Amanda B, Stanford, Janet L, Stevens, Victoria L, Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J, Tajara, Eloiza H, Tangen, Catherine M, Tardon, Adonina, Taylor, Jack A, Teare, M Dawn, Teixeira, Manuel R, Terry, Mary Beth, Terry, Kathryn L, Thibodeau, Stephen N, Thomassen, Mads, Bjørge, Line, Tischkowitz, Marc, Toland, Amanda E, Torres, Diana, Townsend, Paul A, Travis, Ruth C, Tung, Nadine, Tworoger, Shelley S, Ulrich, Cornelia M, Usmani, Nawaid, Vachon, Celine M, Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elías, Wang, Qin, Webb, Penelope M, Weinberg, Clarice R, Weinstein, Stephanie, Weissler, Mark C, Weitzel, Jeffrey N, West, Catharine ML, White, Emily, Whittemore, Alice S, Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H, Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K, Lane, Jacqueline M, Saxena, Richa, Thomas, Duncan, Hung, Rayjean J, Diergaarde, Brenda, McKay, James, Peters, Ulrike, Hsu, Li, García-Closas, Montserrat, Eeles, Rosalind A, Chenevix-Trench, Georgia, Brennan, Paul J, Haiman, Christopher A, Simard, Jacques, Easton, Douglas F, Gruber, Stephen B, Pharoah, Paul DP, Price, Alkes L, Pasaniuc, Bogdan, Amos, Christopher I, Kraft, Peter, and Lindström, Sara
Subjects: Male, Ovarian Neoplasms, Lung Neoplasms, Mental Disorders, Smoking, Inheritance Patterns, Prostatic Neoplasms, Breast Neoplasms, Polymorphism, Single Nucleotide, White People, 3. Good health, Neoplasm Proteins, Phenotype, Head and Neck Neoplasms, Case-Control Studies, Humans, Female, Genetic Predisposition to Disease, Colorectal Neoplasms, Genome-Wide Association Study
Abstract: Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.

42. Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition

Author: Bradbury, Kathryn E, Appleby, Paul N, Tipper, Sarah J, Travis, Ruth C, Allen, Naomi E, Kvaskoff, Marina, Overvad, Kim, Tjønneland, Anne, Halkjaer, Jytte, Cervenka, Iris, Mahamat-Saleh, Yahya, Bonnet, Fabrice, Kaaks, Rudolf, Fortner, Renée T, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Stratigos, Alexander J, Palli, Domenico, Grioni, Sara, Matullo, Giuseppe, Panico, Salvatore, Tumino, Rosario, Peeters, Petra H, Bueno-De-Mesquita, H Bas, Ghiasvand, Reza, Veierød, Marit B, Weiderpass, Elisabete, Bonet, Catalina, Molina, Elena, Huerta, José M, Larrañaga, Nerea, Barricarte, Aurelio, Merino, Susana, Isaksson, Karolin, Stocks, Tanja, Ljuslinder, Ingrid, Hemmingsson, Oskar, Wareham, Nick, Khaw, Kay-Tee, Gunter, Marc J, Rinaldi, Sabina, Tsilidis, Konstantinos K, Aune, Dagfinn, Riboli, Elio, and Key, Timothy J
Subjects: Adult, Male, Nutritional Status, Prostatic Neoplasms, Breast Neoplasms, insulin-like growth factor I, Middle Aged, prospective studies, 3. Good health, Europe, Risk Factors, Case-Control Studies, melanoma, Odds Ratio, biomarker, Humans, Female, EPIC, height, Aged
Abstract: Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma.

43. HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes

Author: Roel Vermeulen, Paulo Bofetta, Nicole Wong Doo, Mark P. Purdue, Eleanor Kane, Gilles Salles, Bengt Glimelius, Christine F. Skibola, Tongzhang Zheng, Graham G. Giles, Scott Davis, Pierluigi Cocco, Karin E. Smedby, Melissa C. Southey, Alexandra Nieters, Elizabeth A. Holly, Corrado Magnani, Paul Brennan, Stephanie J. Lax, David G. Cox, Lindsay M. Morton, Nikolaus Becker, Qing Lan, Elio Riboli, Herve Ghesquieres, Rudolph Kaaks, Jennifer Turner, Martha S. Linet, Anne Kricker, Stephanie J. Weinstein, Christopher R. Flowers, Alain Monnereau, Silvia de Sanjosé, Mary Carrington, John J. Spinelli, Patricia Hartge, Nathaniel Rothman, Yolanda Benavente, Susan L. Slager, Martha Glenn, Richard K. Severson, Ora Paltiel, Yawei Zhang, Ruth C. Travis, Demetrius Albanes, Nicola J. Camp, Paige M. Bracci, Jacqueline Clavel, James R. Cerhan, Marc Maynadié, Maria Grazia Ennas, Marie Hélène Delfau-Larue, Peter Kraft, Henrik Hjalgrim, Roger L. Milne, Alan A. Arslan, Jacob Musinsky, Martyn T. Smith, Anthony Staines, Lauren R. Teras, Jenna M. Voutsinas, Lenka Foretova, Sophia S. Wang, Hans-Olov Adami, Andrew L. Feldman, Wendy Cozen, Angela Brooks-Wilson, Kenneth Offit, Brian K. Link, Brenda M. Birmann, Sonja I. Berndt, Stephen J. Chanock, James McKay, Dennis D. Weisenburger, Claire M. Vajdic, Giancarlo Latte, Karen Curtin, W. Ryan Diver, Mads Melbye, Lucia Conde, Elizabeth E. Brown, Joseph Vijai, Eve Roman, Wang, Sophia S., Carrington, Mary, Berndt, Sonja I., Slager, Susan L., Bracci, Paige M., Voutsinas, Jenna, Cerhan, James R., Smedby, Karin E., Hjalgrim, Henrik, Vijai, Joseph, Morton, Lindsay M., Vermeulen, Roel, Paltiel, Ora, Vajdic, Claire M., Linet, Martha S., Nieters, Alexandra, de Sanjose, Silvia, Cozen, Wendy, Brown, Elizabeth E., Turner, Jennifer, Spinelli, John J., Zheng, Tongzhang, Birmann, Brenda M., Flowers, Christopher R., Becker, Nikolau, Holly, Elizabeth A., Kane, Eleanor, Weisenburger, Denni, Maynadie, Marc, Cocco, Pierluigi, Albanes, Demetriu, Weinstein, Stephanie J., Teras, Lauren R., Diver, W. Ryan, Lax, Stephanie J., Travis, Ruth C., Kaaks, Rudolph, Riboli, Elio, Benavente, Yolanda, Brennan, Paul, McKay, Jame, Delfau-Larue, Marie-Hélène, Link, Brian K., Magnani, Corrado, Ennas, Maria Grazia, Latte, Giancarlo, Feldman, Andrew L., Doo, Nicole Wong, Giles, Graham G., Southey, Melissa C., Milne, Roger L., Offit, Kenneth, Musinsky, Jacob, Arslan, Alan A., Purdue, Mark P., Adami, Hans-Olov, Melbye, Mad, Glimelius, Bengt, Conde, Lucia, Camp, Nicola J., Glenn, Martha, Curtin, Karen, Clavel, Jacqueline, Monnereau, Alain, Cox, David G., Ghesquières, Hervé, Salles, Gille, Boffetta, Paolo, Foretova, Lenka, Staines, Anthony, Davis, Scott, Severson, Richard K., Lan, Qing, Brooks-Wilson, Angela, Smith, Martyn T., Roman, Eve, Kricker, Anne, Zhang, Yawei, Kraft, Peter, Chanock, Stephen J., Rothman, Nathaniel, Hartge, Patricia, and Skibola, Christine F.
Subjects: Male, 0301 basic medicine, Heterozygote, Cancer Research, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Chronic lymphocytic leukemia, EPIDEMIOLOGIC RESEARCH, Genome-wide association study, Human leukocyte antigen, Biology, CLASSIFICATION, ANTIGENS, Article, Genetic Heterogeneity, 03 medical and health sciences, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, INTERLYMPH, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Prospective Studies, GENOME-WIDE ASSOCIATION, Allele, HLA Complex, Science & Technology, Hematology, CHRONIC LYMPHOCYTIC-LEUKEMIA, Genetic heterogeneity, Lymphoma, Non-Hodgkin, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, HETEROZYGOTE ADVANTAGE, medicine.disease, 3. Good health, Lymphoma, 030104 developmental biology, Oncology, Case-Control Studies, Immunology, B-VIRUS INFECTION, Female, Life Sciences & Biomedicine, NEOPLASMS, Genome-Wide Association Study
Abstract: A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086–96. ©2018 AACR.
Published: 2018

44. 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

45. Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Renée T. Fortner, José María Huerta, Roel Vermeulen, Anouar Fanidi, Franco Berrino, H. Bas Bueno-de-Mesquita, Miguel Rodríguez-Barranco, Therese Haugdahl Nøst, Carlo La Vecchia, Rudolf Kaaks, Gianluca Severi, Anne Tjønneland, Eva Ardanaz, Elio Riboli, Antonia Trichopoulou, Kjell Grankvist, Aurélie Affret, Magdalena Stepien, Antonio Agudo, Nerea Larrañaga, Mikael Johansson, David C. Muller, Mattias Johansson, Vittorio Krogh, Elisabete Weiderpass, Hans Brunnström, Domenico Palli, Heinz Freisling, Melissa A. Merritt, Paula Jakszyn, Isabel Drake, Ruth C. Travis, Heiner Boeing, Amanda J. Cross, Marie-Christine Boutron-Ruault, Fulvio Ricceri, Salvatore Panico, Torkjel M. Sandanger, Anastasia Kotanidou, Christina C. Dahm, Julia Whitman, Rosario Tumino, Petra H.M. Peeters, Louise Hansen, Kim Overvad, Heather Ward, José Ramón Quirós, One Health Chemisch, dIRAS RA-2, Department of Medical and Clinical Genetics, University of Helsinki, Faculty of Medicine, Commission of the European Communities, Ward, Heather A, Whitman, Julia, Muller, David C, Johansson, Mattia, Jakszyn, Paula, Weiderpass, Elisabete, Palli, Domenico, Fanidi, Anouar, Vermeulen, Roel, Tjønneland, Anne, Hansen, Louise, Dahm, Christina C, Overvad, Kim, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Affret, Aurélie, Kaaks, Rudolf, Fortner, Renee, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Kotanidou, Anastasia, Berrino, Franco, Krogh, Vittorio, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, H Ba, Peeters, Petra H, Nøst, Therese Haugdahl, Sandanger, Torkjel M, Quirós, Jose Ramón, Agudo, Antonio, Rodríguez-Barranco, Miguel, Larrañaga, Nerea, Huerta, Jose Maria, Ardanaz, Eva, Drake, Isabel, Brunnström, Han, Johansson, Mikael, Grankvist, Kjell, Travis, Ruth C, Freisling, Heinz, Stepien, Magdalena, Merritt, Melissa A, Riboli, Elio, and Cross, Amanda J
Subjects: 0301 basic medicine, Male, Lung Neoplasms, 1106 Human Movement and Sports Sciences, Physiology, Medicine (miscellaneous), MEAT CONSUMPTION, VDP::Medical disciplines: 700::Health sciences: 800::Nutrition: 811, Haem iron, Cohort Studies, ZINC, 0302 clinical medicine, REGRESSION-MODELS, WORLD, Risk Factors, non-haem iron, Cigarette smokers, Fumadors, Prospective Studies, Prospective cohort study, 2. Zero hunger, Nutrition and Dietetics, Confounding, Hazard ratio, digestive, oral, and skin physiology, MUTAGENS, cohort, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Red meat, LIFE-STYLE, Female, dietary iron, 3143 Nutrition, Lung cancer, Life Sciences & Biomedicine, Iron, Dietary, MINERAL INTAKE, SMOKERS, 030209 endocrinology & metabolism, Heme, Risk Assessment, Article, DIET, VDP::Medisinske Fag: 700::Helsefag: 800::Ernæring: 811, 03 medical and health sciences, medicine, Journal Article, Humans, cotinine, Proportional Hazards Models, haem iron, Science & Technology, 030109 nutrition & dietetics, Nutrition & Dietetics, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, business.industry, Proportional hazards model, Case-control study, medicine.disease, PRODUCTS, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, lung cancer, Nutrition Assessment, Risk factors, Case-Control Studies, Càncer de pulmó, 1111 Nutrition and Dietetics, 3111 Biomedicine, business, EPIC, 0908 Food Sciences
Abstract: Accepted manuscript version. Published version available at https://doi.org/10.1038/s41430-018-0271-2. Background: Epidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk using detailed smoking history data and serum cotinine to control for potential confounding. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 416,746 individuals from 10 countries completed demographic and dietary questionnaires at recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident lung cancer (n = 3731) risk relative to haem iron, non-haem iron, and total dietary iron intake. A corresponding analysis was conducted among a nested subset of 800 lung cancer cases and 1489 matched controls for whom serum cotinine was available. Results: Haem iron was associated with lung cancer risk, including after adjustment for details of smoking history (time since quitting, number of cigarettes per day): as a continuous variable (HR per 0.3 mg/1000 kcal 1.03, 95% CI 1.00–1.07), and in the highest versus lowest quintile (HR 1.16, 95% CI 1.02–1.32; trend across quintiles: P = 0.035). In contrast, non-haem iron intake was related inversely with lung cancer risk; however, this association attenuated after adjustment for smoking history. Additional adjustment for serum cotinine did not considerably alter the associations detected in the nested case–control subset. Conclusions: Greater haem iron intake may be modestly associated with lung cancer risk.
Published: 2018

46. Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition

Author: Oskar Hemmingsson, Renée T. Fortner, Marit B. Veierød, Catalina Bonet, Marc J. Gunter, Marina Kvaskoff, Sabina Rinaldi, Susana Merino, Aurelio Barricarte, Kim Overvad, Heiner Boeing, Domenico Palli, Dagfinn Aune, Nerea Larrañaga, Timothy J. Key, José María Huerta, H. Bas Bueno-de-Mesquita, Yahya Mahamat-Saleh, Rudolf Kaaks, Iris Cervenka, Konstantinos K. Tsilidis, Kay-Tee Khaw, Alexander J. Stratigos, Sarah Tipper, Ingrid Ljuslinder, Petra H.M. Peeters, Rosario Tumino, Jytte Halkjær, Salvatore Panico, Ruth C. Travis, Fabrice Bonnet, Paul N. Appleby, Giuseppe Matullo, Carlo La Vecchia, Sara Grioni, Nicholas J. Wareham, Elio Riboli, Reza Ghiasvand, Tanja Stocks, Elena Molina, Kathryn E. Bradbury, Naomi E. Allen, Karolin Isaksson, Antonia Trichopoulou, Elisabete Weiderpass, Anne Tjønneland, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Faculty of Medicine, World Cancer Research Fund International, Bradbury, Kathryn E, Appleby, Paul N, Tipper, Sarah J, Travis, Ruth C, Allen, Naomi E, Kvaskoff, Marina, Overvad, Kim, Tjønneland, Anne, Halkjaer, Jytte, Cervenka, Iri, Mahamat-Saleh, Yahya, Bonnet, Fabrice, Kaaks, Rudolf, Fortner, Renée T, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Stratigos, Alexander J, Palli, Domenico, Grioni, Sara, Matullo, Giuseppe, Panico, Salvatore, Tumino, Rosario, Peeters, Petra H, Bueno-de-Mesquita, H Ba, Ghiasvand, Reza, Veierød, Marit B, Weiderpass, Elisabete, Bonet, Catalina, Molina, Elena, Huerta, José M, Larrañaga, Nerea, Barricarte, Aurelio, Merino, Susana, Isaksson, Karolin, Stocks, Tanja, Ljuslinder, Ingrid, Hemmingsson, Oskar, Wareham, Nick, Khaw, Kay-Tee, Gunter, Marc J, Rinaldi, Sabina, Tsilidis, Konstantinos K, Aune, Dagfinn, Riboli, Elio, Key, Timothy J, Bradbury, Kathryn E [0000-0003-3345-7333], Kvaskoff, Marina [0000-0002-4557-3772], La Vecchia, Carlo [0000-0003-1441-897X], Palli, Domenico [0000-0002-5558-2437], Matullo, Giuseppe [0000-0003-0674-7757], Veierød, Marit B [0000-0002-2083-2758], Ljuslinder, Ingrid [0000-0002-5046-1820], Rinaldi, Sabina [0000-0002-6846-1204], and Apollo - University of Cambridge Repository
Subjects: Oncology, Male, Cancer Research, CUTANEOUS MELANOMA, 030207 dermatology & venereal diseases, 0302 clinical medicine, Risk Factors, Insulina, Odds Ratio, Insulin, Prospective cohort study, Càncer, Breast Neoplasms/etiology, INDEX, Cancer, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Melanoma, Melanoma/etiology, insulin-like growth factor I, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, IGF-I, Europe, Insulin-Like Growth Factor I/metabolism, 030220 oncology & carcinogenesis, Cohort, biomarker, Female, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, 3122 Cancers, Nutritional Status, Breast Neoplasms, 03 medical and health sciences, Internal medicine, medicine, Journal Article, melanoma, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Nutrició, METAANALYSIS, Nutrition, Aged, Science & Technology, Nutritional Status/physiology, business.industry, Kirurgi, Case-control study, Prostatic Neoplasms, Odds ratio, medicine.disease, Confidence interval, prospective studies, Prostatic Neoplasms/etiology, Case-Control Studies, Cutaneous melanoma, CELLS, EPIC, height, Surgery, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract: Source at https://doi.org/10.1002/ijc.31854. Insulin‐like growth factor‐I (IGF‐I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF‐I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF‐I concentrations and melanoma risk. A nested case–control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF‐I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF‐I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF‐I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF‐I measured in adulthood and the risk of melanoma.
Published: 2018

47. Pre-diagnostic circulating insulin-like growth factor-I and bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition

Author: Virginia Menéndez, Crystal Lin, Nina Roswall, Marc J. Gunter, Rudolf Kaaks, Petra H.M. Peeters, Elisabete Weiderpass, Paul N. Appleby, Anne Tjønneland, Inger T. Gram, Maria Dolores Chirlaque, Fredrik Liedberg, Sarah J. Tipper, Lambertus A. Kiemeney, Leila Lujan-Barroso, Elio Riboli, Claudia Agnoli, Elena Salamanca-Fernández, Antonia Trichopoulou, Francesca Romana Manciniveri, Kim Overvad, Timothy J. Key, Gianluca Severi, Eva Ardanaz, Rosario Tumino, Heinz Freisling, Bas Bueno-de-Mesquita, Ruth C. Travis, Giovanna Masala, Jenny Chang-Claude, Carlotta Sacerdote, Börje Ljungberg, Amanda J. Cross, Miren Dorronsoro, Dagfinn Aune, Aurora Perez-Cornago, Marie-Christine Boutron-Ruault, Salvatore Panico, Universitat de Barcelona, Imperial College Trust, Lin, Crystal, Travis, Ruth C, Appleby, Paul N, Tipper, Sarah, Weiderpass, Elisabete, Chang-Claude, Jenny, Gram, Inger T, Kaaks, Rudolf, Kiemeney, Lambertus A, Ljungberg, Börje, Tumino, Rosario, Tjønneland, Anne, Roswall, Nina, Overvad, Kim, Boutron-Ruault, Marie-Christine, Manciniveri, Francesca Romana, Severi, Gianluca, Trichopoulou, Antonia, Masala, Giovanna, Sacerdote, Carlotta, Agnoli, Claudia, Panico, Salvatore, Bueno-de-Mesquita, Ba, Peeters, Petra H, Salamanca-Fernández, Elena, Chirlaque, Maria-Dolore, Ardanaz, Eva, Dorronsoro, Miren, Menéndez, Virginia, Luján-Barroso, Leila, Liedberg, Fredrik, Freisling, Heinz, Gunter, Marc, Aune, Dagfinn, Cross, Amanda J, Riboli, Elio, Key, Timothy J, and Perez-Cornago, Aurora
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, EPIC cohort, FACTOR (IGF)-I, Prostate cancer, 0302 clinical medicine, MOLECULAR SUBTYPES, Prospective Studies, Insulin-Like Growth Factor I, Prospective cohort study, IGF‐I, IGF BINDING PROTEIN-3, Factors de risc en les malalties, Bladder cancer, ASSOCIATION, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, PROSTATE-CANCER, IGF-I, Europe, FACTOR RECEPTOR, 030220 oncology & carcinogenesis, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Cohort, bladder cancer, Female, Life Sciences & Biomedicine, Cancer Epidemiology, Adult, Risk, medicine.medical_specialty, Risk factors in diseases, Short Report, Càncer de bufeta, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, VDP::Medisinske Fag: 700, Oncology & Carcinogenesis, PLASMA-LEVELS, METAANALYSIS, Aged, Tumors, Science & Technology, business.industry, Case-control study, Cancer, IGFBP-3, Odds ratio, prospective, medicine.disease, VDP::Medical disciplines: 700, 030104 developmental biology, Urinary Bladder Neoplasms, urothelial cell carcinoma, Case-Control Studies, CELLS, business
Abstract: Previous in vitro and case–control studies have found an association between the insulin‐like growth factor (IGF)‐axis and bladder cancer risk. Circulating concentrations of IGF‐I have also been found to be associated with an increased risk of several cancer types; however, the relationship between pre‐diagnostic circulating IGF‐I concentrations and bladder cancer has never been studied prospectively. We investigated the association of pre‐diagnostic plasma concentrations of IGF‐I with risk of overall bladder cancer and urothelial cell carcinoma (UCC) in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 843 men and women diagnosed with bladder cancer between 1992 and 2005 were matched with 843 controls by recruitment centre, sex, age at recruitment, date of blood collection, duration of follow‐up, time of day and fasting status at blood collection using an incidence density sampling protocol. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for smoking status. No association was found between pre‐diagnostic circulating IGF‐I concentration and overall bladder cancer risk (adjusted OR for highest versus lowest fourth: 0.91, 95% CI: 0.66–1.24, p trend = 0.40) or UCC (n of cases = 776; 0.91, 0.65–1.26, p trend = 0.40). There was no significant evidence of heterogeneity in the association of IGF‐I with bladder cancer risk by tumour aggressiveness, sex, smoking status, or by time between blood collection and diagnosis (p heterogeneity > 0.05 for all). This first prospective study indicates no evidence of an association between plasma IGF‐I concentrations and bladder cancer risk., What's new? Past prospective studies have shown a positive association between circulating insulin‐like growth factor I (IGF‐I) concentration and colorectal, prostate, and breast cancer risk. However, the association between circulating IGF‐I concentrations and bladder cancer risk remains uncertain. Using a nested‐case control study with 843 bladder cancer cases across 9 European countries, for the first time here the authors examined prospectively the association between pre‐diagnostic circulating IGF‐I concentrations and bladder cancer risk. IGF‐I was not associated with overall risk of bladder cancer or urothelial cell carcinoma. Further prospective data, including on tumour aggressiveness, are required to examine the association in greater detail.
Published: 2018

48. Prediction of acute myeloid leukaemia risk in healthy individuals

Author: Aurelio Barricarte, Claire Hardy, Kristian M. Bowles, Abigail Britten, Mattias Johansson, Sabina Sieri, Kay-Tee Khaw, Sagi Abelson, Philip A. Beer, Stanley W.K. Ng, Matthieu Foll, Lee Timms, Diana Hoult, Salvatore Panico, Shabina Hayat, Elena Salamanca-Fernández, Paul M. Krzyzanowski, Rosario Tumino, Noam Barda, José María Huerta, Lawrence E. Heisler, Jean C.Y. Wang, Inigo Martincorena, Mark D. Minden, Robert Luben, John E. Dick, Trevor J. Pugh, Sam Behjati, Anna Karakatsani, Philip Awadalla, Carlo La Vecchia, Zhen Zhao, Ruth C. Travis, Iulia Cirlan, Omer Weissbrod, Giovanna Masala, Heiner Boeing, Rui Costa, Elio Riboli, Nicholas J. Wareham, Calli Latimer, Philip C. Zuzarte, David T. Jones, Ting Ting Wang, J. Ramón Quirós, Grace Collord, Peter J. Campbell, Roel Vermeulen, Yogi Sundaravadanam, Elli Papaemmanuil, Antonia Trichopoulou, Ran D. Balicer, James McKay, Alwin Krämer, Jessica Miller, Keiran Raine, Jenna Eagles, Paolo Vineis, Netta Mendelson Cohen, Silvia Polidoro, Scott V. Bratman, Amos Tanay, Moritz Gerstung, George S. Vassiliou, Paul Brennan, Eran Segal, Karen Ng, Rudolf Kaaks, Núria Sala, David Soave, Faridah Mbabaali, Danielle Pasternack, Liran I. Shlush, John Douglas Mcpherson, Elisabeth Niemeyer, One Health Chemisch, dIRAS RA-2, Abelson, Sagi, Collord, Grace, Ng, Stanley W K, Weissbrod, Omer, Mendelson Cohen, Netta, Niemeyer, Elisabeth, Barda, Noam, Zuzarte, Philip C, Heisler, Lawrence, Sundaravadanam, Yogi, Luben, Robert, Hayat, Shabina, Wang, Ting Ting, Zhao, Zhen, Cirlan, Iulia, Pugh, Trevor J, Soave, David, Ng, Karen, Latimer, Calli, Hardy, Claire, Raine, Keiran, Jones, David, Hoult, Diana, Britten, Abigail, Mcpherson, John D, Johansson, Mattia, Mbabaali, Faridah, Eagles, Jenna, Miller, Jessica K, Pasternack, Danielle, Timms, Lee, Krzyzanowski, Paul, Awadalla, Philip, Costa, Rui, Segal, Eran, Bratman, Scott V, Beer, Philip, Behjati, Sam, Martincorena, Inigo, Wang, Jean C Y, Bowles, Kristian M, Quirós, J Ramón, Karakatsani, Anna, La Vecchia, Carlo, Trichopoulou, Antonia, Salamanca-Fernández, Elena, Huerta, José M, Barricarte, Aurelio, Travis, Ruth C, Tumino, Rosario, Masala, Giovanna, Boeing, Heiner, Panico, Salvatore, Kaaks, Rudolf, Krämer, Alwin, Sieri, Sabina, Riboli, Elio, Vineis, Paolo, Foll, Matthieu, Mckay, Jame, Polidoro, Silvia, Sala, Núria, Khaw, Kay-Tee, Vermeulen, Roel, Campbell, Peter J, Papaemmanuil, Elli, Minden, Mark D, Tanay, Amo, Balicer, Ran D, Wareham, Nicholas J, Gerstung, Moritz, Dick, John E, Brennan, Paul, Vassiliou, George S, Shlush, Liran I, Italian Institute for Genomic Medicine IIGM, Collord, Grace [0000-0003-1924-4411], Luben, Robert [0000-0002-5088-6343], Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Vassiliou, George [0000-0003-4337-8022], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Oncology, Myeloid, Male, 0302 clinical medicine, Models, hemic and lymphatic diseases, Prevalence, 2.1 Biological and endogenous factors, Electronic Health Records, Aetiology, Cells, Cultured, Cancer, Pediatric, screening and diagnosis, Multidisciplinary, Leukemia, Incidence (epidemiology), Age Factors, CLONAL HEMATOPOIESIS, Hematology, Middle Aged, CANCER, 3. Good health, Multidisciplinary Sciences, Haematopoiesis, Detection, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Myeloid leukemia, Health, 030220 oncology & carcinogenesis, Cohort, Disease Progression, Science & Technology - Other Topics, Female, Adult, medicine.medical_specialty, Pediatric Cancer, Childhood Leukemia, General Science & Technology, Leucèmia mieloide, MODELS, Acute, Risk Assessment, CLASSIFICATION, Article, 03 medical and health sciences, Rare Diseases, Genetic, Cancer stem cell, Internal medicine, MD Multidisciplinary, medicine, Genetics, Mortalitat, Humans, Genetic Predisposition to Disease, Progenitor cell, Mortality, neoplasms, Aged, Science & Technology, Models, Genetic, business.industry, Prevention, SOMATIC MUTATIONS, medicine.disease, EVOLUTION, Hematopoiesis, 4.1 Discovery and preclinical testing of markers and technologies, 030104 developmental biology, Good Health and Well Being, Mutagenesis, Mutation, PATTERNS, Bone marrow, business
Abstract: The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure(1). The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion(2,3). However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)(4-8). Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.
Published: 2018

49. Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort

Author: Mattias Johansson, Elena Molina-Portillo, Pietro Ferrari, Rudolf Kaaks, Julie A. Schmidt, Anastasia Kotanidou, Petra H.M. Peeters, Eline H. van Roekel, Augustin Scalbert, Domenico Palli, Khalid Iqbal, Rosario Tumino, Heiner Boeing, José María Huerta, Matty P. Weijenberg, Marie-Christine Boutron-Ruault, Laura Trijsburg, Ruth C. Travis, Fulvio Ricceri, Miren Dorronsoro, Neil Murphy, Antonia Trichopoulou, Agnetha Linn Rostgaard-Hansen, Anne Tjønneland, Anders Håkansson, Sabina Rinaldi, Elio Riboli, Tilman Kühn, J. Ramón Quirós, Leila Lujan-Barroso, Konstantinos K. Tsilidis, Elisabete Weiderpass, Magdalena Stepien, Salvatore Panico, Gianluca Severi, Eva Ardanaz, Bas Bueno-de-Mesquita, Anna Karakatsani, Marion Carayol, Nada Assi, David Achaintre, Mazda Jenab, Kim Overvad, Johan Malm, Marc J. Gunter, Vittorio Krogh, Imperial College Trust, RS: GROW - R1 - Prevention, Epidemiologie, Beleid Economie & Organisatie vd Zorg, van Roekel, Eline H, Trijsburg, Laura, Assi, Nada, Carayol, Marion, Achaintre, David, Murphy, Neil, Rinaldi, Sabina, Schmidt, Julie A, Stepien, Magdalena, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Iqbal, Khalid, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Peeters, Petra H, Bueno-de-Mesquita, Ba, Ardanaz, Eva, Lujan-Barroso, Leila, Quirós, J Ramón, Huerta, José M, Molina-Portillo, Elena, Dorronsoro, Miren, Tsilidis, Konstantinos K, Riboli, Elio, Rostgaard-Hansen, Agnetha Linn, Tjønneland, Anne, Overvad, Kim, Weiderpass, Elisabete, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Trichopoulou, Antonia, Karakatsani, Anna, Kotanidou, Anastasia, Håkansson, Ander, Malm, Johan, Weijenberg, Matty P, Gunter, Marc J, Jenab, Mazda, Johansson, Mattia, Travis, Ruth C, Scalbert, Augustin, and Ferrari, Pietro
Subjects: Male, Metabolite, Physiology, lipid metabolite, Alcohol, Sex Factor, Alcohol Drinking/adverse effects, chemistry.chemical_compound, 0302 clinical medicine, acylcarnitines, Risk Factors, Tandem Mass Spectrometry, Neoplasms, Metabolites, Smoking/adverse effects, Citrulline, targeted metabolomics, Medicine, 030212 general & internal medicine, Prospective Studies, Càncer, Prospective cohort study, Biotransformation, Chromatography, High Pressure Liquid, Cancer, RISK, Chromatography, Nutrition and Dietetics, PLASMA, alcohol, Smoking, targeted metabolomic, VDP::Medical disciplines: 700::Health sciences: 800, Lipid, Middle Aged, Metabòlits, Lipids, FALSE DISCOVERY RATE, APOPTOSIS, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, acylcamitines, VDP::Medisinske Fag: 700::Helsefag: 800, Drinking of alcoholic beverages, 030220 oncology & carcinogenesis, High Pressure Liquid, ACID, Neoplasms/blood, Cohort, Consum d'alcohol, POPULATIONS, amino acids, lipid metabolites, Aged, Alcohol Drinking, Biomarkers, Female, Humans, Metabolomics, Self Report, Sex Factors, Life Style, Nutritional Status, Europa, lcsh:Nutrition. Foods and food supply, amino acid, Human, Metabolomic, lcsh:TX341-641, Article, acylcarnitine, 03 medical and health sciences, Metabolomics/methods, SPHINGOMYELINASE, Lipids/blood, business.industry, Risk Factor, CONSUMPTION, Biomarker, Prospective Studie, Metabolic pathway, PHYSICAL-ACTIVITY, chemistry, Neoplasm, 1111 Nutrition And Dietetics, business, Biomarkers/blood, Food Science
Abstract: Source at https://doi.org/10.3390/nu10050654. Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions
Published: 2018

50. Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study

Author: Eleni Maria Papatesta, Antonia Trichopoulou, Pietro Ferrari, Michael J. Sweeting, Calogero Saieva, Rodolfo Saracci, Fabrice Bonnet, Diana Gavrila, Elisabete Weiderpass, W M Monique Verschuren, Timothy J. Key, Ioanna Tzoulaki, Larraitz Arriola, Cristian Ricci, Jan-Håkan Jansson, Jolanda M. A. Boer, Claudia Agnoli, Rosario Tumino, Paul Brennan, Nicholas J. Wareham, Marc J. Gunter, Ivonne Sluijs, Heinz Freisling, David C. Muller, Rudolf Kaaks, Nita G. Forouhi, Conchi Moreno Iribas, Eleni Peppa, Camille Lassale, Kim Overvad, Stephen J. Sharp, Salvatore Panico, Ann-Sofie Forslund, Angela M. Wood, Domenico Palli, Olle Melander, María José Sánchez, Cecilie Kyrø, John Danesh, Annemieke M.W. Spijkerman, J. Ramón Quirós, Yvonne T. van der Schouw, Claudia Langenberg, Antonio Agudo, Ruth C. Travis, Anne Tjønneland, Tilman Kühn, Adam S. Butterworth, Gunnar Engström, Elio Riboli, Giuseppe Matullo, Samantha Warnakula, Heiner Boeing, University of Helsinki, Clinicum, Ricci, Cristian, Wood, Angela, Muller, David, Gunter, Marc J, Agudo, Antonio, Boeing, Heiner, van der Schouw, Yvonne T, Warnakula, Samantha, Saieva, Calogero, Spijkerman, Annemieke, Sluijs, Ivonne, Tjønneland, Anne, Kyrø, Cecilie, Weiderpass, Elisabete, Kühn, Tilman, Kaaks, Rudolf, Sánchez, Maria-Jose, Panico, Salvatore, Agnoli, Claudia, Palli, Domenico, Tumino, Rosario, Engström, Gunnar, Melander, Olle, Bonnet, Fabrice, Boer, Jolanda M A, Key, Timothy J, Travis, Ruth C, Overvad, Kim, Verschuren, W M Monique, Quirós, J Ramón, Trichopoulou, Antonia, Papatesta, Eleni-Maria, Peppa, Eleni, Iribas, Conchi Moreno, Gavrila, Diana, Forslund, Ann-Sofie, Jansson, Jan-Håkan, Matullo, Giuseppe, Arriola, Larraitz, Freisling, Heinz, Lassale, Camille, Tzoulaki, Ioanna, Sharp, Stephen J, Forouhi, Nita G, Langenberg, Claudia, Saracci, Rodolfo, Sweeting, Michael, Brennan, Paul, Butterworth, Adam S, Riboli, Elio, Wareham, Nick J, Danesh, John, and Ferrari, Pietro
Subjects: Male, Time Factors, Stroke/classification, Coronary Artery Disease, 030204 cardiovascular system & hematology, Body Mass Index, Alcohol Drinking/adverse effects, 0302 clinical medicine, Cause of Death, Smoking/adverse effects, Medicine, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Stroke, Cause of death, Medicine(all), Kardiologi, Medicine (all), Hazard ratio, Smoking, INDIVIDUAL-PARTICIPANT DATA, General Medicine, Middle Aged, CANCER, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, CARDIOVASCULAR-DISEASE, Cohort, LIFE-STYLE, Female, Coronary Artery Disease/classification, Drug, Life Sciences & Biomedicine, Human, Cohort study, medicine.medical_specialty, Alcohol Drinking, Endpoint Determination, 1117 Public Health and Health Services, Dose-Response Relationship, 03 medical and health sciences, Medicine, General & Internal, POLYPHENOLS, Internal medicine, General & Internal Medicine, Humans, cardiovascular diseases, Exercise, METAANALYSIS, Science & Technology, Dose-Response Relationship, Drug, business.industry, Research, 1103 Clinical Sciences, CAUSE-SPECIFIC MORTALITY, CONSUMPTION, SMOKING-CESSATION, medicine.disease, Prospective Studie, 3121 General medicine, internal medicine and other clinical medicine, RISK-FACTORS, Risk Reduction Behavior, business, Body mass index
Abstract: OBJECTIVE:To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. DESIGN:Multicentre case-cohort study. SETTING:A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. PARTICIPANTS:32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. MAIN OUTCOME MEASURES:Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). RESULTS:There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. CONCLUSIONS:Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.
Published: 2018

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