Search

Your search keyword '"Severi, Gianluca"' showing total 81 results
Start Over Author "Severi, Gianluca" Topic middle aged
81 results on '"Severi, Gianluca"'

1. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study

Author

Haycock, Philip C, Burgess, Stephen, Nounu, Aayah, Zheng, Jie, Okoli, George N, Bowden, Jack, Wade, Kaitlin Hazel, Timpson, Nicholas J, Evans, David M, Willeit, Peter, Aviv, Abraham, Gaunt, Tom R, Hemani, Gibran, Mangino, Massimo, Ellis, Hayley Patricia, Kurian, Kathreena M, Pooley, Karen A, Eeles, Rosalind A, Lee, Jeffrey E, Fang, Shenying, Chen, Wei V, Law, Matthew H, Bowdler, Lisa M, Iles, Mark M, Yang, Qiong, Worrall, Bradford B, Markus, Hugh Stephen, Hung, Rayjean J, Amos, Chris I, Spurdle, Amanda B, Thompson, Deborah J, O’Mara, Tracy A, Wolpin, Brian, Amundadottir, Laufey, Stolzenberg-Solomon, Rachael, Trichopoulou, Antonia, Onland-Moret, N Charlotte, Lund, Eiliv, Duell, Eric J, Canzian, Federico, Severi, Gianluca, Overvad, Kim, Gunter, Marc J, Tumino, Rosario, Svenson, Ulrika, van Rij, Andre, Baas, Annette F, Bown, Matthew J, Samani, Nilesh J, van t’Hof, Femke NG, Tromp, Gerard, Jones, Gregory T, Kuivaniemi, Helena, Elmore, James R, Johansson, Mattias, Mckay, James, Scelo, Ghislaine, Carreras-Torres, Robert, Gaborieau, Valerie, Brennan, Paul, Bracci, Paige M, Neale, Rachel E, Olson, Sara H, Gallinger, Steven, Li, Donghui, Petersen, Gloria M, Risch, Harvey A, Klein, Alison P, Han, Jiali, Abnet, Christian C, Freedman, Neal D, Taylor, Philip R, Maris, John M, Aben, Katja K, Kiemeney, Lambertus A, Vermeulen, Sita H, Wiencke, John K, Walsh, Kyle M, Wrensch, Margaret, Rice, Terri, Turnbull, Clare, Litchfield, Kevin, Paternoster, Lavinia, Standl, Marie, Abecasis, Gonçalo R, SanGiovanni, John Paul, Li, Yong, Mijatovic, Vladan, Sapkota, Yadav, Low, Siew-Kee, Zondervan, Krina T, Montgomery, Grant W, Nyholt, Dale R, van Heel, David A, Hunt, Karen, Arking, Dan E, Ashar, Foram N, Sotoodehnia, Nona, Woo, Daniel, and Rosand, Jonathan

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Clinical Research, Cancer, Prevention, Genetics, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Germ-Line Mutation, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Neoplasms, Polymorphism, Single Nucleotide, Risk Assessment, Telomere, Telomere Homeostasis, Telomeres Mendelian Randomization Collaboration, Public Health and Health Services, Oncology and carcinogenesis
Abstract

ImportanceThe causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.ObjectiveTo conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.Data sourcesGenomewide association studies (GWAS) published up to January 15, 2015.Study selectionGWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.Data extraction and synthesisSummary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.Main outcomes and measuresOdds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.ResultsSummary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]).Conclusions and relevanceIt is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

Published
2017

2. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.

Author

Telomeres Mendelian Randomization Collaboration, Haycock, Philip C, Burgess, Stephen, Nounu, Aayah, Zheng, Jie, Okoli, George N, Bowden, Jack, Wade, Kaitlin Hazel, Timpson, Nicholas J, Evans, David M, Willeit, Peter, Aviv, Abraham, Gaunt, Tom R, Hemani, Gibran, Mangino, Massimo, Ellis, Hayley Patricia, Kurian, Kathreena M, Pooley, Karen A, Eeles, Rosalind A, Lee, Jeffrey E, Fang, Shenying, Chen, Wei V, Law, Matthew H, Bowdler, Lisa M, Iles, Mark M, Yang, Qiong, Worrall, Bradford B, Markus, Hugh Stephen, Hung, Rayjean J, Amos, Chris I, Spurdle, Amanda B, Thompson, Deborah J, O'Mara, Tracy A, Wolpin, Brian, Amundadottir, Laufey, Stolzenberg-Solomon, Rachael, Trichopoulou, Antonia, Onland-Moret, N Charlotte, Lund, Eiliv, Duell, Eric J, Canzian, Federico, Severi, Gianluca, Overvad, Kim, Gunter, Marc J, Tumino, Rosario, Svenson, Ulrika, van Rij, Andre, Baas, Annette F, Bown, Matthew J, Samani, Nilesh J, van t'Hof, Femke NG, Tromp, Gerard, Jones, Gregory T, Kuivaniemi, Helena, Elmore, James R, Johansson, Mattias, Mckay, James, Scelo, Ghislaine, Carreras-Torres, Robert, Gaborieau, Valerie, Brennan, Paul, Bracci, Paige M, Neale, Rachel E, Olson, Sara H, Gallinger, Steven, Li, Donghui, Petersen, Gloria M, Risch, Harvey A, Klein, Alison P, Han, Jiali, Abnet, Christian C, Freedman, Neal D, Taylor, Philip R, Maris, John M, Aben, Katja K, Kiemeney, Lambertus A, Vermeulen, Sita H, Wiencke, John K, Walsh, Kyle M, Wrensch, Margaret, Rice, Terri, Turnbull, Clare, Litchfield, Kevin, Paternoster, Lavinia, Standl, Marie, Abecasis, Gonçalo R, SanGiovanni, John Paul, Li, Yong, Mijatovic, Vladan, Sapkota, Yadav, Low, Siew-Kee, Zondervan, Krina T, Montgomery, Grant W, Nyholt, Dale R, van Heel, David A, Hunt, Karen, Arking, Dan E, Ashar, Foram N, Sotoodehnia, Nona, and Woo, Daniel

Subjects
Telomeres Mendelian Randomization Collaboration, Telomere, Humans, Neoplasms, Cardiovascular Diseases, Genetic Predisposition to Disease, Risk Assessment, Germ-Line Mutation, Polymorphism, Single Nucleotide, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study, Mendelian Randomization Analysis, Telomere Homeostasis, Polymorphism, Single Nucleotide, and over, Prevention, Clinical Research, Cancer, Genetics, Rare Diseases, 2.1 Biological and endogenous factors, Oncology and Carcinogenesis, Public Health and Health Services
Abstract

ImportanceThe causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.ObjectiveTo conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.Data sourcesGenomewide association studies (GWAS) published up to January 15, 2015.Study selectionGWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.Data extraction and synthesisSummary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.Main outcomes and measuresOdds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.ResultsSummary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]).Conclusions and relevanceIt is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

Published
2017

3. A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

Author

Travis, Ruth C, Appleby, Paul N, Martin, Richard M, Holly, Jeff MP, Albanes, Demetrius, Black, Amanda, Bueno-de-Mesquita, HB As, Chan, June M, Chen, Chu, Chirlaque, Maria-Dolores, Cook, Michael B, Deschasaux, Mélanie, Donovan, Jenny L, Ferrucci, Luigi, Galan, Pilar, Giles, Graham G, Giovannucci, Edward L, Gunter, Marc J, Habel, Laurel A, Hamdy, Freddie C, Helzlsouer, Kathy J, Hercberg, Serge, Hoover, Robert N, Janssen, Joseph AMJL, Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Metter, E Jeffrey, Mikami, Kazuya, Morris, Joan K, Neal, David E, Neuhouser, Marian L, Ozasa, Kotaro, Palli, Domenico, Platz, Elizabeth A, Pollak, Michael, Price, Alison J, Roobol, Monique J, Schaefer, Catherine, Schenk, Jeannette M, Severi, Gianluca, Stampfer, Meir J, Stattin, Pär, Tamakoshi, Akiko, Tangen, Catherine M, Touvier, Mathilde, Wald, Nicholas J, Weiss, Noel S, Ziegler, Regina G, Key, Timothy J, and Allen, Naomi E

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Aging, Prostate Cancer, Cancer, Urologic Diseases, Aged, Humans, Insulin-Like Growth Factor I, Male, Middle Aged, Prostatic Neoplasms, Risk Factors, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.

Published
2016

4. 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

5. Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies 1–3

Author

Key, Timothy J, Appleby, Paul N, Travis, Ruth C, Albanes, Demetrius, Alberg, Anthony J, Barricarte, Aurelio, Black, Amanda, Boeing, Heiner, Bueno-de-Mesquita, H Bas, Chan, June M, Chen, Chu, Cook, Michael B, Donovan, Jenny L, Galan, Pilar, Gilbert, Rebecca, Giles, Graham G, Giovannucci, Edward, Goodman, Gary E, Goodman, Phyllis J, Gunter, Marc J, Hamdy, Freddie C, Heliövaara, Markku, Helzlsouer, Kathy J, Henderson, Brian E, Hercberg, Serge, Hoffman-Bolton, Judy, Hoover, Robert N, Johansson, Mattias, Khaw, Kay-Tee, King, Irena B, Knekt, Paul, Kolonel, Laurence N, Le Marchand, Loic, Männistö, Satu, Martin, Richard M, Meyer, Haakon E, Mondul, Alison M, Moy, Kristin A, Neal, David E, Neuhouser, Marian L, Palli, Domenico, Platz, Elizabeth A, Pouchieu, Camille, Rissanen, Harri, Schenk, Jeannette M, Severi, Gianluca, Stampfer, Meir J, Tjønneland, Anne, Touvier, Mathilde, Trichopoulou, Antonia, Weinstein, Stephanie J, Ziegler, Regina G, Zhou, Cindy Ke, Allen, Naomi E, Biomarkers, Endogenous Hormones Nutritional, and Group, Prostate Cancer Collaborative

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Urologic Diseases, Nutrition, Prostate Cancer, Cancer, Aging, Clinical Research, Adult, Biomarkers, Carotenoids, Case-Control Studies, Cohort Studies, Cross-Sectional Studies, Humans, Lycopene, Male, Meta-Analysis as Topic, Middle Aged, Neoplasm Grading, Neoplasm Staging, Observational Studies as Topic, Prospective Studies, Prostate, Prostatic Neoplasms, Risk Factors, Vitamin A, alpha-Tocopherol, prostate cancer, carotenoids, retinol, tocopherols, vitamin E, vitamin A, pooled analysis, nested case-control study, biomarkers, Endogenous Hormones Nutritional Biomarkers Prostate Cancer Collaborative Group, Engineering, Medical and Health Sciences, Nutrition & Dietetics, Clinical sciences, Nutrition and dietetics
Abstract

BackgroundIndividual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.ObjectiveThe objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, α-tocopherol, and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors.DesignPrincipal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets.ResultsData were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For α-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). γ-Tocopherol was not associated with risk.ConclusionsOverall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol. Whether these associations reflect causal relations is unclear.

Published
2015

6. 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

7. Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study.

Author

Johnson, Nichola, Dudbridge, Frank, Orr, Nick, Gibson, Lorna, Jones, Michael E, Schoemaker, Minouk J, Folkerd, Elizabeth J, Haynes, Ben P, Hopper, John L, Southey, Melissa C, Dite, Gillian S, Apicella, Carmel, Schmidt, Marjanka K, Broeks, Annegien, Van't Veer, Laura J, Atsma, Femke, Muir, Kenneth, Lophatananon, Artitaya, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Renner, Stefan P, Sawyer, Elinor, Tomlinson, Ian, Kerin, Michael, Miller, Nicola, Burwinkel, Barbara, Marme, Frederik, Schneeweiss, Andreas, Sohn, Christof, Guénel, Pascal, Truong, Therese, Cordina, Emilie, Menegaux, Florence, Bojesen, Stig E, Nordestgaard, Børge G, Flyger, Henrik, Milne, Roger, Zamora, M Pilar, Arias Perez, Jose Ignacio, Benitez, Javier, Bernstein, Leslie, Anton-Culver, Hoda, Ziogas, Argyrios, Clarke Dur, Christina, Brenner, Hermann, Müller, Heiko, Arndt, Volker, Dieffenbach, Aida Karina, Meindl, Alfons, Heil, Joerg, Bartram, Claus R, Schmutzler, Rita K, Brauch, Hiltrud, Justenhoven, Christina, Ko, Yon-Dschun, GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network, Nevanlinna, Heli, Muranen, Taru A, Aittomäki, Kristiina, Blomqvist, Carl, Matsuo, Keitaro, Dörk, Thilo, Bogdanova, Natalia V, Antonenkova, Natalia N, Lindblom, Annika, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M, Chenevix-Trench, Georgia, Beesley, Jonathan, kConFab Investigators, Australian Ovarian Cancer Study Group, Wu, Anna H, Van den Berg, David, Tseng, Chiu-Chen, Lambrechts, Diether, Smeets, Dominiek, Neven, Patrick, Wildiers, Hans, Chang-Claude, Jenny, Rudolph, Anja, Nickels, Stefan, Flesch-Janys, Dieter, Radice, Paolo, Peterlongo, Paolo, Bonanni, Bernardo, Pensotti, Valeria, Couch, Fergus J, Olson, Janet E, Wang, Xianshu, Fredericksen, Zachary, Pankratz, Vernon S, Giles, Graham G, Severi, Gianluca, Baglietto, Laura, Haiman, Chris, Simard, Jacques, and Goldberg, Mark S

Subjects
GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network, kConFab Investigators, Australian Ovarian Cancer Study Group, Humans, Breast Neoplasms, Genetic Predisposition to Disease, Reproductive History, Risk Factors, Age Factors, Age of Onset, Premenopause, Menarche, Genotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, European Continental Ancestry Group, Female, Cytochrome P-450 CYP3A, Genetic Association Studies, Human Genome, Aging, Clinical Research, Cancer, Genetics, Breast Cancer, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract

IntroductionWe have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.MethodsWe further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.ResultsWe confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29).ConclusionsTo our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

Published
2014

8. Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer.

Author

Purrington, Kristen, Slager, Susan, Eccles, Diana, Yannoukakos, Drakoulis, Fasching, Peter, Miron, Penelope, Carpenter, Jane, Chang-Claude, Jenny, Martin, Nicholas, Montgomery, Grant, Kristensen, Vessela, Goodfellow, Paul, Tapper, William, Rafiq, Sajjad, Gerty, Susan, Durcan, Lorraine, Konstantopoulou, Irene, Fostira, Florentia, Vratimos, Athanassios, Apostolou, Paraskevi, Konstanta, Irene, Kotoula, Vassiliki, Lakis, Sotiris, Dimopoulos, Meletios, Skarlos, Dimosthenis, Pectasides, Dimitrios, Fountzilas, George, Beckmann, Matthias, Hein, Alexander, Ruebner, Matthias, Ekici, Arif, Hartmann, Arndt, Schulz-Wendtland, Ruediger, Renner, Stefan, Janni, Wolfgang, Rack, Brigitte, Scholz, Christoph, Neugebauer, Julia, Andergassen, Ulrich, Lux, Michael, Haeberle, Lothar, Clarke, Christine, Pathmanathan, Nirmala, Rudolph, Anja, Flesch-Janys, Dieter, Nickels, Stefan, Olson, Janet, Ingle, James, Olswold, Curtis, Slettedahl, Seth, Eckel-Passow, Jeanette, Anderson, S, Visscher, Daniel, Cafourek, Victoria, Sicotte, Hugues, Prodduturi, Naresh, Weiderpass, Elisabete, Bernstein, Leslie, Ivanovich, Jennifer, Giles, Graham, Baglietto, Laura, Southey, Melissa, Kosma, Veli-Matti, Fischer, Hans-Peter, Reed, Malcom, Cross, Simon, Deming-Halverson, Sandra, Shrubsole, Martha, Cai, Qiuyin, Shu, Xiao-Ou, Daly, Mary, Weaver, Joellen, Ross, Eric, Klemp, Jennifer, Sharma, Priyanka, Torres, Diana, Rüdiger, Thomas, Wölfing, Heidrun, Ulmer, Hans-Ulrich, Försti, Asta, Khoury, Thaer, Kumar, Shicha, Pilarski, Robert, Shapiro, Charles, Greco, Dario, Heikkilä, Päivi, Aittomäki, Kristiina, Blomqvist, Carl, Irwanto, Astrid, Liu, Jianjun, Pankratz, Vernon, Wang, Xianshu, Severi, Gianluca, Mannermaa, Arto, Easton, Douglas, Hall, Per, Brauch, Hiltrud, Cox, Angela, Zheng, Wei, and Godwin, Andrew

Subjects
Adult, Aged, Aged, 80 and over, Case-Control Studies, Chromosomes, Human, Pair 19, Estrogen Receptor alpha, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Triple Negative Breast Neoplasms, Young Adult
Abstract

Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.

Published
2014

9. Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

Author

Sawyer, Elinor, Roylance, Rebecca, Petridis, Christos, Brook, Mark, Nowinski, Salpie, Papouli, Efterpi, Fletcher, Olivia, Pinder, Sarah, Hanby, Andrew, Kohut, Kelly, Gorman, Patricia, Caneppele, Michele, Peto, Julian, Dos Santos Silva, Isabel, Johnson, Nichola, Swann, Ruth, Dwek, Miriam, Perkins, Katherine-Anne, Gillett, Cheryl, Houlston, Richard, Ross, Gillian, De Ieso, Paolo, Southey, Melissa, Hopper, John, Provenzano, Elena, Apicella, Carmel, Wesseling, Jelle, Cornelissen, Sten, Keeman, Renske, Fasching, Peter, Jud, Sebastian, Ekici, Arif, Beckmann, Matthias, Kerin, Michael, Marme, Federick, Schneeweiss, Andreas, Sohn, Christof, Burwinkel, Barbara, Guénel, Pascal, Truong, Therese, Laurent-Puig, Pierre, Kerbrat, Pierre, Bojesen, Stig, Nordestgaard, Børge, Nielsen, Sune, Flyger, Henrik, Milne, Roger, Perez, Jose, Menéndez, Primitiva, Benitez, Javier, Brenner, Hermann, Dieffenbach, Aida, Arndt, Volker, Stegmaier, Christa, Meindl, Alfons, Lichtner, Peter, Schmutzler, Rita, Lochmann, Magdalena, Brauch, Hiltrud, Fischer, Hans-Peter, Ko, Yon-Dschun, Nevanlinna, Heli, Muranen, Taru, Aittomäki, Kristiina, Blomqvist, Carl, Bogdanova, Natalia, Dörk, Thilo, Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana, Chenevix-Trench, Georgia, Lambrechts, Diether, Weltens, Caroline, Van Limbergen, Erik, Hatse, Sigrid, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Radice, Paolo, Peterlongo, Paolo, Bonanni, Bernardo, Volorio, Sara, Giles, Graham, Severi, Gianluca, Baglietto, Laura, McLean, Catriona, Haiman, Christopher, Henderson, Brian, Schumacher, Fredrick, Le Marchand, Loic, Simard, Jacques, Goldberg, Mark, Labrèche, France, Dumont, Martine, Kristensen, Vessela, and Winqvist, Robert

Subjects
Breast Neoplasms, Carcinoma in Situ, Carcinoma, Lobular, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Middle Aged, Polymorphism, Single Nucleotide
Abstract

Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P

Published
2014

10. Identification of New Genetic Susceptibility Loci for Breast Cancer Through Consideration of Gene‐Environment Interactions

Author

Schoeps, Anja, Rudolph, Anja, Seibold, Petra, Dunning, Alison M, Milne, Roger L, Bojesen, Stig E, Swerdlow, Anthony, Andrulis, Irene, Brenner, Hermann, Behrens, Sabine, Orr, Nicholas, Jones, Michael, Ashworth, Alan, Li, Jingmei, Cramp, Helen, Connley, Dan, Czene, Kamila, Darabi, Hatef, Chanock, Stephen J, Lissowska, Jolanta, Figueroa, Jonine D, Knight, Julia, Glendon, Gord, Mulligan, Anna M, Dumont, Martine, Severi, Gianluca, Baglietto, Laura, Olson, Janet, Vachon, Celine, Purrington, Kristen, Moisse, Matthieu, Neven, Patrick, Wildiers, Hans, Spurdle, Amanda, Kosma, Veli‐Matti, Kataja, Vesa, Hartikainen, Jaana M, Hamann, Ute, Ko, Yon‐Dschun, Dieffenbach, Aida K, Arndt, Volker, Stegmaier, Christa, Malats, Núria, Perez, José I Arias, Benítez, Javier, Flyger, Henrik, Nordestgaard, Børge G, Truong, Thérèse, Cordina‐Duverger, Emilie, Menegaux, Florence, dos Santos Silva, Isabel, Fletcher, Olivia, Johnson, Nichola, Häberle, Lothar, Beckmann, Matthias W, Ekici, Arif B, Braaf, Linde, Atsma, Femke, Broek, Alexandra J den, Makalic, Enes, Schmidt, Daniel F, Southey, Melissa C, Cox, Angela, Simard, Jacques, Giles, Graham G, Lambrechts, Diether, Mannermaa, Arto, Brauch, Hiltrud, Guénel, Pascal, Peto, Julian, Fasching, Peter A, Hopper, John, Flesch‐Janys, Dieter, Couch, Fergus, Chenevix‐Trench, Georgia, Pharoah, Paul DP, Garcia‐Closas, Montserrat, Schmidt, Marjanka K, Hall, Per, Easton, Douglas F, and Chang‐Claude, Jenny

Subjects
Biological Sciences, Genetics, Epidemiology, Health Services and Systems, Health Sciences, Genetic Testing, Human Genome, Prevention, Breast Cancer, Aging, Clinical Research, Cancer, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Body Height, Body Mass Index, Breast Neoplasms, Chromosomes, Human, Pair 21, Chromosomes, Human, Pair 6, Female, Gene-Environment Interaction, Genetic Loci, Genetic Predisposition to Disease, Humans, Linkage Disequilibrium, Menarche, Middle Aged, Parity, Polymorphism, Single Nucleotide, Postmenopause, White People, breast cancer risk, gene-environment interaction, polymorphisms, body mass index, case-control study, Public Health and Health Services
Abstract

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15-1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72-1.11, P for interaction = 3.2 × 10(-05)). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci.

Published
2014

11. Genome-wide association study of glioma and meta-analysis

Author

Rajaraman, Preetha, Melin, Beatrice S, Wang, Zhaoming, McKean-Cowdin, Roberta, Michaud, Dominique S, Wang, Sophia S, Bondy, Melissa, Houlston, Richard, Jenkins, Robert B, Wrensch, Margaret, Yeager, Meredith, Ahlbom, Anders, Albanes, Demetrius, Andersson, Ulrika, Freeman, Laura E Beane, Buring, Julie E, Butler, Mary Ann, Braganza, Melissa, Carreon, Tania, Feychting, Maria, Fleming, Sarah J, Gapstur, Susan M, Gaziano, J Michael, Giles, Graham G, Hallmans, Goran, Henriksson, Roger, Hoffman-Bolton, Judith, Inskip, Peter D, Johansen, Christoffer, Kitahara, Cari M, Lathrop, Mark, Liu, Chenwei, Le Marchand, Loic, Linet, Martha S, Lonn, Stefan, Peters, Ulrike, Purdue, Mark P, Rothman, Nathaniel, Ruder, Avima M, Sanson, Marc, Sesso, Howard D, Severi, Gianluca, Shu, Xiao-Ou, Simon, Matthias, Stampfer, Meir, Stevens, Victoria L, Visvanathan, Kala, White, Emily, Wolk, Alicja, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Decker, Paul, Enciso-Mora, Victor, Fridley, Brooke, Gao, Yu-Tang, Kosel, Matthew, Lachance, Daniel H, Lau, Ching, Rice, Terri, Swerdlow, Anthony, Wiemels, Joseph L, Wiencke, John K, Shete, Sanjay, Xiang, Yong-Bing, Xiao, Yuanyuan, Hoover, Robert N, Fraumeni, Joseph F, Chatterjee, Nilanjan, Hartge, Patricia, and Chanock, Stephen J

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Research, Brain Disorders, Prevention, Brain Cancer, Neurosciences, Cancer, Human Genome, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Aged, Brain Neoplasms, Case-Control Studies, Cohort Studies, Cyclin-Dependent Kinase Inhibitor p15, DNA Helicases, Female, Genome-Wide Association Study, Glioblastoma, Glioma, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Telomerase, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.

Published
2012

12. CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer.

Author

Weischer, Maren, Nordestgaard, Børge G, Pharoah, Paul, Bolla, Manjeet K, Nevanlinna, Heli, Van't Veer, Laura J, Garcia-Closas, Montserrat, Hopper, John L, Hall, Per, Andrulis, Irene L, Devilee, Peter, Fasching, Peter A, Anton-Culver, Hoda, Lambrechts, Diether, Hooning, Maartje, Cox, Angela, Giles, Graham G, Burwinkel, Barbara, Lindblom, Annika, Couch, Fergus J, Mannermaa, Arto, Grenaker Alnæs, Grethe, John, Esther M, Dörk, Thilo, Flyger, Henrik, Dunning, Alison M, Wang, Qin, Muranen, Taru A, van Hien, Richard, Figueroa, Jonine, Southey, Melissa C, Czene, Kamila, Knight, Julia A, Tollenaar, Rob AEM, Beckmann, Matthias W, Ziogas, Argyrios, Christiaens, Marie-Rose, Collée, Johanna Margriet, Reed, Malcolm WR, Severi, Gianluca, Marme, Frederik, Margolin, Sara, Olson, Janet E, Kosma, Veli-Matti, Kristensen, Vessela N, Miron, Alexander, Bogdanova, Natalia, Shah, Mitul, Blomqvist, Carl, Broeks, Annegien, Sherman, Mark, Phillips, Kelly-Anne, Li, Jingmei, Liu, Jianjun, Glendon, Gord, Seynaeve, Caroline, Ekici, Arif B, Leunen, Karin, Kriege, Mieke, Cross, Simon S, Baglietto, Laura, Sohn, Christof, Wang, Xianshu, Kataja, Vesa, Børresen-Dale, Anne-Lise, Meyer, Andreas, Easton, Douglas F, Schmidt, Marjanka K, and Bojesen, Stig E

Subjects
Humans, Breast Neoplasms, Neoplasms, Second Primary, Genetic Predisposition to Disease, Prognosis, Case-Control Studies, Prospective Studies, Genotype, Heterozygote, Germ-Line Mutation, Middle Aged, Female, Checkpoint Kinase 2, Protein Serine-Threonine Kinases, Breast Cancer, Clinical Research, Cancer, Prevention, Genetics, Estrogen, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeWe tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer.Patients and methodsFrom 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer-specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies.ResultsCHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor-positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer-specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor-positive first breast cancer only.ConclusionAmong women with estrogen receptor-positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer-specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer.

Published
2012

13. Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2.

Author

Kirchhoff, Tomas, Gaudet, Mia M, Antoniou, Antonis C, McGuffog, Lesley, Humphreys, Manjeet K, Dunning, Alison M, Bojesen, Stig E, Nordestgaard, Børge G, Flyger, Henrik, Kang, Daehee, Yoo, Keun-Young, Noh, Dong-Young, Ahn, Sei-Hyun, Dork, Thilo, Schürmann, Peter, Karstens, Johann H, Hillemanns, Peter, Couch, Fergus J, Olson, Janet, Vachon, Celine, Wang, Xianshu, Cox, Angela, Brock, Ian, Elliott, Graeme, Reed, Malcolm WR, Burwinkel, Barbara, Meindl, Alfons, Brauch, Hiltrud, Hamann, Ute, Ko, Yon-Dschun, GENICA Network, Broeks, Annegien, Schmidt, Marjanka K, Van 't Veer, Laura J, Braaf, Linde M, Johnson, Nichola, Fletcher, Olivia, Gibson, Lorna, Peto, Julian, Turnbull, Clare, Seal, Sheila, Renwick, Anthony, Rahman, Nazneen, Wu, Pei-Ei, Yu, Jyh-Cherng, Hsiung, Chia-Ni, Shen, Chen-Yang, Southey, Melissa C, Hopper, John L, Hammet, Fleur, Van Dorpe, Thijs, Dieudonne, Anne-Sophie, Hatse, Sigrid, Lambrechts, Diether, Andrulis, Irene L, Bogdanova, Natalia, Antonenkova, Natalia, Rogov, Juri I, Prokofieva, Daria, Bermisheva, Marina, Khusnutdinova, Elza, van Asperen, Christi J, Tollenaar, Robert AEM, Hooning, Maartje J, Devilee, Peter, Margolin, Sara, Lindblom, Annika, Milne, Roger L, Arias, José Ignacio, Zamora, M Pilar, Benítez, Javier, Severi, Gianluca, Baglietto, Laura, Giles, Graham G, kConFab, AOCS Study Group, Spurdle, Amanda B, Beesley, Jonathan, Chen, Xiaoqing, Holland, Helene, Healey, Sue, Wang-Gohrke, Shan, Chang-Claude, Jenny, Mannermaa, Arto, Kosma, Veli-Matti, Kauppinen, Jaana, Kataja, Vesa, Agnarsson, Bjarni A, Caligo, Maria A, Godwin, Andrew K, Nevanlinna, Heli, Heikkinen, Tuomas, Fredericksen, Zachary, Lindor, Noralane, Nathanson, Katherine L, Domchek, Susan M, SWE-BRCA, Loman, Niklas, Karlsson, Per, and Stenmark Askmalm, Marie

Subjects
GENICA Network, kConFab, AOCS Study Group, SWE-BRCA, HEBON, EMBRACE, BCAC/CIMBA, Chromosomes, Human, Pair 6, Humans, Breast Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, BRCA2 Protein, Receptors, Estrogen, Confidence Intervals, Proportional Hazards Models, Odds Ratio, Risk Factors, Heterozygote, Polymorphism, Single Nucleotide, Alleles, Middle Aged, Female, Genetic Association Studies, Chromosomes, Human, Pair 6, Polymorphism, Single Nucleotide, Receptors, Estrogen, General Science & Technology
Abstract

Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p =

Published
2012

14. Association Between a Germline OCA2 Polymorphism at Chromosome 15q13.1 and Estrogen Receptor–Negative Breast Cancer Survival

Author

Azzato, Elizabeth M, Tyrer, Jonathan, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Schulz-Wendtland, Rüdiger, Bojesen, Stig E, Nordestgaard, Børge G, Flyger, Henrik, Milne, Roger L, Arias, José Ignacio, Menéndez, Primitiva, Benítez, Javier, Chang-Claude, Jenny, Hein, Rebecca, Wang-Gohrke, Shan, Nevanlinna, Heli, Heikkinen, Tuomas, Aittomäki, Kristiina, Blomqvist, Carl, Margolin, Sara, Mannermaa, Arto, Kosma, Veli-Matti, Kataja, Vesa, Beesley, Jonathan, Chen, Xiaoqing, Chenevix-Trench, Georgia, Couch, Fergus J, Olson, Janet E, Fredericksen, Zachary S, Wang, Xianshu, Giles, Graham G, Severi, Gianluca, Baglietto, Laura, Southey, Melissa C, Devilee, Peter, Tollenaar, Rob AEM, Seynaeve, Caroline, García-Closas, Montserrat, Lissowska, Jolanta, Sherman, Mark E, Bolton, Kelly L, Hall, Per, Czene, Kamila, Cox, Angela, Brock, Ian W, Elliott, Graeme C, Reed, Malcolm WR, Greenberg, David, Anton-Culver, Hoda, Ziogas, Argyrios, Humphreys, Manjeet, Easton, Douglas F, Caporaso, Neil E, and Pharoah, Paul DP

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Genetics, Breast Cancer, Human Genome, Cancer, Adult, Aged, Alleles, Biomarkers, Tumor, Breast Neoplasms, Chromosomes, Human, Pair 15, Female, Genotype, Germ-Line Mutation, Humans, Membrane Transport Proteins, Middle Aged, Polymorphism, Single Nucleotide, Proportional Hazards Models, Receptors, Estrogen, Research Design, Risk Assessment, Risk Factors, Survival Analysis, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundTraditional prognostic factors for survival and treatment response of patients with breast cancer do not fully account for observed survival variation. We used available genotype data from a previously conducted two-stage, breast cancer susceptibility genome-wide association study (ie, Studies of Epidemiology and Risk factors in Cancer Heredity [SEARCH]) to investigate associations between variation in germline DNA and overall survival.MethodsWe evaluated possible associations between overall survival after a breast cancer diagnosis and 10 621 germline single-nucleotide polymorphisms (SNPs) from up to 3761 patients with invasive breast cancer (including 647 deaths and 26 978 person-years at risk) that were genotyped previously in the SEARCH study with high-density oligonucleotide microarrays (ie, hypothesis-generating set). Associations with all-cause mortality were assessed for each SNP by use of Cox regression analysis, generating a per rare allele hazard ratio (HR). To validate putative associations, we used patient genotype information that had been obtained with 5' nuclease assay or mass spectrometry and overall survival information for up to 14 096 patients with invasive breast cancer (including 2303 deaths and 70 019 person-years at risk) from 15 international case-control studies (ie, validation set). Fixed-effects meta-analysis was used to generate an overall effect estimate in the validation dataset and in combined SEARCH and validation datasets. All statistical tests were two-sided.ResultsIn the hypothesis-generating dataset, SNP rs4778137 (C>G) of the OCA2 gene at 15q13.1 was statistically significantly associated with overall survival among patients with estrogen receptor-negative tumors, with the rare G allele being associated with increased overall survival (HR of death per rare allele carried = 0.56, 95% confidence interval [CI] = 0.41 to 0.75, P = 9.2 x 10(-5)). This association was also observed in the validation dataset (HR of death per rare allele carried = 0.88, 95% CI = 0.78 to 0.99, P = .03) and in the combined dataset (HR of death per rare allele carried = 0.82, 95% CI = 0.73 to 0.92, P = 5 x 10(-4)).ConclusionThe rare G allele of the OCA2 polymorphism, rs4778137, may be associated with improved overall survival among patients with estrogen receptor-negative breast cancer.

Published
2010

15. Risk of Estrogen Receptor–Positive and –Negative Breast Cancer and Single–Nucleotide Polymorphism 2q35-rs13387042

Author

Milne, Roger L, Benítez, Javier, Nevanlinna, Heli, Heikkinen, Tuomas, Aittomäki, Kristiina, Blomqvist, Carl, Arias, José Ignacio, Zamora, M Pilar, Burwinkel, Barbara, Bartram, Claus R, Meindl, Alfons, Schmutzler, Rita K, Cox, Angela, Brock, Ian, Elliott, Graeme, Reed, Malcolm WR, Southey, Melissa C, Smith, Letitia, Spurdle, Amanda B, Hopper, John L, Couch, Fergus J, Olson, Janet E, Wang, Xianshu, Fredericksen, Zachary, Schürmann, Peter, Bremer, Michael, Hillemanns, Peter, Dörk, Thilo, Devilee, Peter, van Asperen, Christie J, Tollenaar, Rob AEM, Seynaeve, Caroline, Hall, Per, Czene, Kamila, Liu, Jianjun, Li, Yuqing, Ahmed, Shahana, Dunning, Alison M, Maranian, Melanie, Pharoah, Paul DP, Chenevix-Trench, Georgia, Beesley, Jonathan, Investigators, kConFab, Group, AOCS, Bogdanova, Natalia V, Antonenkova, Natalia N, Zalutsky, Iosif V, Anton-Culver, Hoda, Ziogas, Argyrios, Brauch, Hiltrud, Justenhoven, Christina, Ko, Yon-Dschun, Haas, Susanne, Fasching, Peter A, Strick, Reiner, Ekici, Arif B, Beckmann, Matthias W, Giles, Graham G, Severi, Gianluca, Baglietto, Laura, English, Dallas R, Fletcher, Olivia, Johnson, Nichola, dos Santos Silva, Isabel, Peto, Julian, Turnbull, Clare, Hines, Sarah, Renwick, Anthony, Rahman, Nazneen, Nordestgaard, Børge G, Bojesen, Stig E, Flyger, Henrik, Kang, Daehee, Yoo, Keun-Young, Noh, Dong-Young, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, García-Closas, Montserrat, Chanock, Stephen, Lissowska, Jolanta, Brinton, Louise A, Chang-Claude, Jenny, Wang-Gohrke, Shan, Shen, Chen-Yang, Wang, Hui-Chun, Yu, Jyh-Cherng, Chen, Sou-Tong, Bermisheva, Marina, Nikolaeva, Tatjana, Khusnutdinova, Elza, Humphreys, Manjeet K, Morrison, Jonathan, Platte, Radka, Easton, Douglas F, and Consortium, on behalf of the Breast Cancer Association

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Breast Cancer, Clinical Research, Cancer, Human Genome, Estrogen, Adult, Aged, Asian People, Biomarkers, Tumor, Breast Neoplasms, Carcinoma, Ductal, Breast, Carcinoma, Intraductal, Noninfiltrating, Case-Control Studies, Confidence Intervals, Confounding Factors, Epidemiologic, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Linkage Disequilibrium, Middle Aged, Neoplasms, Hormone-Dependent, Odds Ratio, Polymorphism, Single Nucleotide, Receptors, Estrogen, Receptors, Progesterone, White People, kConFab Investigators, AOCS Group, Breast Cancer Association Consortium, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundA recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium.Methods2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided.ResultsWe found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; P(trend) = 1.0 x 10(-19)). The odds ratio was lower than that previously reported (P = .02) and did not vary by age or ethnicity (all P > or = .2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10(-15)) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P = .0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 x 10(-14)) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P = .00002).ConclusionThe rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.

Published
2009

16. Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort

Author

Deschasaux-Tanguy, Mélanie, Srour, Bernard, Bourhis, Laurent, Arnault, Nathalie, Druesne-Pecollo, Nathalie, Esseddik, Younes, de Edelenyi, Fabien Szabo, Allègre, Julien, Allès, Benjamin, Andreeva, Valentina A., Baudry, Julia, Fezeu, Leopold K., Galan, Pilar, Julia, Chantal, Kesse-Guyot, Emmanuelle, Péneau, Sandrine, Hercberg, Serge, Bajos, Nathalie, Severi, Gianluca, Zins, Marie, de Lamballerie, Xavier, Carrat, Fabrice, Touvier, Mathilde, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut de Recherche Interdisciplinaire sur les enjeux Sociaux - sciences sociales, politique, santé (IRIS), École des hautes études en sciences sociales (EHESS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Sorbonne Paris Nord, 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), Università degli Studi di Firenze = University of Florence (UniFI), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), The SAPRIS/SAPRIS-SERO projects received funding from ANR (Agence Nationale de la Recherche, #ANR-20-COVI-000, #ANR-10-COHO-06), Fondation pour la Recherche Médicale (#20RR052-00), and Inserm (InstitutNational de la Santé et de la Recherche Médicale, #C20-26). The NutriNetSanté cohort study was supported by the following public institutions: Ministère de la Santé, Santé Publique France, Institut National de la Santé et de laRecherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Conservatoire National des Arts et Métiers (CNAM) and Université Sorbonne Paris Nord. Study investigators are independent from the funders. Funders had no role in the study design, the collection, analysis, and interpretation of data, the writing of themanuscript, or the decision to submit the article for publication., SAPRIS-SERO study group: Fabrice Carrat, Pierre-Yves Ancel, Nathalie Bajos, Marie-Aline Charles, Gianluca Severi, Mathilde Touvier, Marie Zins, Sofiane Kab, Adeline Renuy, Stephane Le-Got, Celine Ribet, Emmanuel Wiernik, Marcel Goldberg, Marie Zins, Fanny Artaud, Pascale Gerbouin-Rérolle, Mélody Enguix, Camille Laplanche, Roselyn Gomes-Rima, Lyan Hoang, Emmanuelle Correia, Alpha Amadou Barry, Nadège Senina, Gianluca Severi, Fabien Szabo de Edelenyi, Julien Allègre, Nathalie Druesne-Pecollo, Younes Esseddik, Serge Hercberg, Mathilde Touvier, Marie-Aline Charles, Pierre-Yves Ancel, Valérie Benhammou, Anass Ritmi, Laetitia Marchand, Cecile Zaros, Elodie Lordmi, Adriana Candea, Sophie de Visme, Thierry Simeon, Xavier Thierry, Bertrand Geay, Marie-Noelle Dufourg, Karen Milcent, Clovis Lusivika-Nzinga, Gregory Pannetier, Nathanael Lapidus, Isabelle Goderel, Céline Dorival, Jérôme Nicol, Fabrice Carrat, Cindy Lai, Hélène Esperou, Sandrine Couffin-Cadiergues, Jean-Marie Gagliolo, Hélène Blanché, Jean-Marc Sébaoun, Jean-Christophe Beaudoin, Laetitia Gressin, Valérie Morel, Ouissam Ouili, Jean-François Deleuze, Stéphane Priet, Paola Mariela Saba Villarroel, Toscane Fourié, Souand Mohamed Ali, Abdenour Amroun, Morgan Seston, Nazli Ayhan, Boris Pastorino, Xavier de Lamballerie, European Project: 637408,NHMRC::Early Career Fellowships(2010), Malbec, Odile, INSERM - - NHMRC::Early Career Fellowships2010-01-01 - 2010-12-31 - 637408 - VALID, Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord-École des hautes études en sciences sociales (EHESS), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ANR-20-COVI-0009,SAPRIS,Santé, perception, pratiques, relations et inégalités sociales en population générale pendant la crise COVID-19(2020)

Subjects
Adult, Male, SARS-CoV-2, [SDV]Life Sciences [q-bio], COVID-19, Seroprevalence, Vitamins, Middle Aged, Diet, Cohort Studies, [SDV] Life Sciences [q-bio], Risk Factors, Seroepidemiologic Studies, Humans, Female, Prospective Studies, Cohort study, Pandemics, Research Article
Abstract

Background Nutritional factors are essential for the functioning of the immune system and could therefore play a role in COVID-19 but evidence is needed. Our objective was to study the associations between diet and the risk of SARS-CoV-2 infection in a large population-based sample. Methods Our analyses were conducted in the French prospective NutriNet-Santé cohort study (2009–2020). Seroprevalence of anti-SARS-CoV-2 antibodies was assessed by ELISA on dried blood spots. Dietary intakes were derived from repeated 24 h dietary records (at least 6) in the two years preceding the start of the COVID-19 pandemic in France (February 2020). Multi-adjusted logistic regression models were computed. Results A total of 7766 adults (70.3% women, mean age: 60.3 years) were included, among which 311 were positive for anti-SARS-CoV-2 antibodies. Dietary intakes of vitamin C (OR for 1 SD=0.86 (0.75–0.98), P=0.02), vitamin B9 (OR=0.84 (0.72–0.98), P=0.02), vitamin K (OR=0.86 (0.74–0.99), P=0.04), fibers (OR=0.84 (0.72–0.98), P=0.02), and fruit and vegetables (OR=0.85 (0.74–0.97), P=0.02) were associated to a decreased probability of SARS-CoV-2 infection while dietary intakes of calcium (OR=1.16 (1.01–1.35), P=0.04) and dairy products (OR=1.19 (1.06–1.33), P=0.002) associated to increased odds. No association was detected with other food groups or nutrients or with the overall diet quality. Conclusions Higher dietary intakes of fruit and vegetables and, consistently, of vitamin C, folate, vitamin K and fibers were associated with a lower susceptibility to SARS-CoV-2 infection. Beyond its established role in the prevention of non-communicable diseases, diet could therefore also contribute to prevent some infectious diseases such as COVID-19. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-021-02168-1.

Published
2021

17. Use of systemic glucocorticoids and risk of breast cancer in a prospective cohort of postmenopausal women

Author

Cairat, Manon, Al Rahmoun, Marie, Gunter, Marc, Heudel, Pierre-Etienne, Severi, Gianluca, Dossus, Laure, Fournier, Agnès, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Léon Bérard [Lyon], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Università degli Studi di Firenze = University of Florence (UniFI), ANR-10-COHO-0006,E4N,Etude Epidémiologique des Enfants de femmes de l'Education Nationale(2010), Malbec, Odile, and Cohortes - Etude Epidémiologique des Enfants de femmes de l'Education Nationale - - E4N2010 - ANR-10-COHO-0006 - COHO - VALID

Subjects
Pharmacoepidemiology, [SDV]Life Sciences [q-bio], Cancer stage, Cohort, Breast Neoplasms, Middle Aged, Risk Assessment, Postmenopausal women, [SDV] Life Sciences [q-bio], Postmenopause, Breast cancer, Molecular status, Risk Factors, Oestrogen receptors, Humans, Medicine, Female, Prospective Studies, Glucocorticoids, Proportional Hazards Models, Research Article
Abstract

Background Glucocorticoids could theoretically decrease breast cancer risk through their anti-inflammatory effects or increase risk through immunosuppression. However, epidemiological evidence is limited regarding the associations between glucocorticoid use and breast cancer risk. Methods We investigated the association between systemic glucocorticoid use and breast cancer incidence in the E3N cohort, which includes 98,995 women with information on various characteristics collected from repeated questionnaires complemented with drug reimbursement data available from 2004. Women with at least two reimbursements of systemic glucocorticoids in any previous 3-month period since January 1, 2004, were defined as exposed. We considered exposure as a time-varying parameter, and we used multivariable Cox regression models to estimate hazard ratios (HRs) of breast cancer. We performed a competing risk analysis using a cause-specific hazard approach to study the heterogeneity by tumour subtype/stage/grade. Results Among 62,512 postmenopausal women (median age at inclusion of 63 years old), 2864 developed breast cancer during a median follow-up of 9 years (between years 2004 and 2014). Compared with non-exposure, glucocorticoid exposure was not associated with overall breast cancer risk [HR = 0.94 (0.85–1.05)]; however, it was associated with a higher risk of in situ breast cancer and a lower risk of invasive breast cancer [HRinsitu = 1.34 (1.01–1.78); HRinvasive = 0.86 (0.76–0.97); Phomogeneity = 0.01]. Regarding the risk of invasive breast cancer, glucocorticoid exposure was inversely associated with oestrogen receptor (ER)-positive breast cancer [HRER+ = 0.82 (0.72–0.94); HRER− = 1.21 (0.88–1.66); Phomogeneity = 0.03]; it was also inversely associated with the risk of stage 1 or stage 2 tumours but positively associated with the risk of stage 3/4 breast cancers [HRstage1 = 0.87 (0.75–1.01); HRstage2 = 0.67 (0.52–0.86); HRstage3/4 = 1.49 (1.02–2.20); Phomogeneity = 0.01]. Conclusion This study suggests that the association between systemic glucocorticoid use and breast cancer risk may differ by tumour subtype and stage. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-021-02004-6.

Published
2021

18. Monitoring the proportion of the population infected by SARS-CoV-2 using age-stratified hospitalisation and serological data: a modelling study

Author

Hozé, Nathanaël, Paireau, Juliette, Lapidus, Nathanaël, Tran Kiem, Cécile, Salje, Henrik, Severi, Gianluca, Touvier, Mathilde, Zins, Marie, De Lamballerie, Xavier, Lévy-Bruhl, Daniel, Carrat, Fabrice, Cauchemez, Simon, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université - Département de santé publique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), University of Cambridge [UK] (CAM), 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, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sorbonne Université - Faculté de Médecine (SU FM), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Support for this study was provided by Agence Nationale de la Recherche (ANR, ANR-20-COVI-000, #ANR-10-COHO-06), Fondation pour la Recherche Médicale (#20RR052-00), Institut National de la Santé et de la Recherche Médicale (Inserm, C20-26). We acknowledge financial support from the Investissement d'Avenir programme, the Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases programme (grant ANR-10-LABX-62-IBEID), Santé Publique France, the INCEPTION project (PIA/ANR-16-CONV-0005), the EU Horizon 2020 research and innovation programme under grants 101003589 (RECOVER) and 874735 (VEO), AXA, and Groupama. The CONSTANCES Cohort Study is supported by the Caisse Nationale d'Assurance Maladie, the French Ministry of Health, the Ministry of Research, and Inserm. CONSTANCES benefits from a grant from the French National Research Agency (grant number ANR-11-INBS-0002) and is also partly funded by Merck Sharp & Dohme, AstraZeneca, Lundbeck, and L'Oreal. The E3N-E4N cohort is supported by the following institutions: Ministère de l'Enseignement Supérieur, de la Recherche et de l'Innovation, Inserm, University Paris-Saclay, Gustave Roussy, the Mutuelle générale de l'Éducation nationale, and the French League Against Cancer. The NutriNet-Santé study is supported by the following public institutions: Ministère de la Santé, Santé Publique France, Inserm, Institut National de la Recherche Agronomique, Conservatoire National des Arts et Métiers, and Sorbonne Paris Nord. The CEPH-Biobank is supported by the Ministère de l'Enseignement Supérieur, de la Recherche et de l'Innovation., ANR-10-COHO-0006,E4N,Etude Epidémiologique des Enfants de femmes de l'Education Nationale(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 874735,VEO, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Collège Doctoral, Università degli Studi di Firenze = University of Florence (UniFI), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), European Project: 874735,H2020-SC1-2019-Single-Stage-RTD,VEO(2020), Salje, Henrik [0000-0003-3626-4254], Apollo - University of Cambridge Repository, Gestionnaire, HAL Sorbonne Université 5, Cohortes - Etude Epidémiologique des Enfants de femmes de l'Education Nationale - - E4N2010 - ANR-10-COHO-0006 - COHO - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, and Versatile Emerging infectious disease Observatory - VEO - - H2020-SC1-2019-Single-Stage-RTD2020-01-01 - 2024-12-31 - 874735 - VALID

Subjects
Adult, Models, Statistical, COVID-19, Articles, Middle Aged, Hospitalization, Young Adult, Age Distribution, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Seroepidemiologic Studies, Humans, Public Health Surveillance, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Aged
Abstract

BACKGROUND: Regional monitoring of the proportion of the population who have been infected by SARS-CoV-2 is important to guide local management of the epidemic, but is difficult in the absence of regular nationwide serosurveys. We aimed to estimate in near real time the proportion of adults who have been infected by SARS-CoV-2. METHODS: In this modelling study, we developed a method to reconstruct the proportion of adults who have been infected by SARS-CoV-2 and the proportion of infections being detected, using the joint analysis of age-stratified seroprevalence, hospitalisation, and case data, with deconvolution methods. We developed our method on a dataset consisting of seroprevalence estimates from 9782 participants (aged ≥20 years) in the two worst affected regions of France in May, 2020, and applied our approach to the 13 French metropolitan regions over the period March, 2020, to January, 2021. We validated our method externally using data from a national seroprevalence study done between May and June, 2020. FINDINGS: We estimate that 5·7% (95% CI 5·1-6·4) of adults in metropolitan France had been infected with SARS-CoV-2 by May 11, 2020. This proportion remained stable until August, 2020, and increased to 14·9% (13·2-16·9) by Jan 15, 2021. With 26·5% (23·4-29·8) of adult residents having been infected in Île-de-France (Paris region) compared with 5·1% (4·5-5·8) in Brittany by January, 2021, regional variations remained large (coefficient of variation [CV] 0·50) although less so than in May, 2020 (CV 0·74). The proportion infected was twice as high (20·4%, 15·6-26·3) in 20-49-year-olds than in individuals aged 50 years or older (9·7%, 6·9-14·1). 40·2% (34·3-46·3) of infections in adults were detected in June to August, 2020, compared with 49·3% (42·9-55·9) in November, 2020, to January, 2021. Our regional estimates of seroprevalence were strongly correlated with the external validation dataset (coefficient of correlation 0·89). INTERPRETATION: Our simple approach to estimate the proportion of adults that have been infected with SARS-CoV-2 can help to characterise the burden of SARS-CoV-2 infection, epidemic dynamics, and the performance of surveillance in different regions. FUNDING: EU RECOVER, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Institut National de la Santé et de la Recherche Médicale (Inserm).

Published
2021

19. Incidence and risk factors of COVID-19-like symptoms in the French general population during the lockdown period: a multi-cohort study

Author

Carrat, Fabrice, Touvier, Mathilde, Severi, Gianluca, Meyer, Laurence, Jusot, Florence, Lapidus, Nathanael, Rahib, Delphine, Lydié, Nathalie, Charles, Marie-Aline, Ancel, Pierre-Yves, Rouquette, Alexandra, De Lamballerie, Xavier, Zins, Marie, Bajos, Nathalie, Study Group, SAPRIS, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire d'Economie de Dauphine (LEDa), Institut de Recherche pour le Développement (IRD)-Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), Institut de Recherche Interdisciplinaire sur les enjeux Sociaux - sciences sociales, politique, santé (IRIS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord-École des hautes études en sciences sociales (EHESS), French National Research Agency (ANR)ANR-20-COVI-000Fondation pour la Recherche Medicale20RR052-00Institut National de la Sante et de la Recherche Medicale (Inserm)C20-26Caisse Nationale d'Assurance Maladie (CNAM), ANR-10-COHO-0006,E4N,Etude Epidémiologique des Enfants de femmes de l'Education Nationale(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université - Département de santé publique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli Studi di Firenze = University of Florence (UniFI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), École des hautes études en sciences sociales (EHESS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Sorbonne Paris Nord, ANR-11-INBS-0002,CONSTANCES,La cohorte CONSTANCES - Infrastructure épidémiologique ouverte pour la recherche et la surveillance(2011), Gestionnaire, HAL Sorbonne Université 5, Cohortes - Etude Epidémiologique des Enfants de femmes de l'Education Nationale - - E4N2010 - ANR-10-COHO-0006 - COHO - VALID, and Infrastructures - La cohorte CONSTANCES - Infrastructure épidémiologique ouverte pour la recherche et la surveillance - - CONSTANCES2011 - ANR-11-INBS-0002 - INBS - VALID

Subjects
Male, Pediatrics, MESH: Comorbidity, Comorbidity, 030204 cardiovascular system & hematology, Overweight, Cohort Studies, MESH: Communicable Disease Control, 0302 clinical medicine, MESH: Risk Factors, MESH: Child, Epidemiology, Prevalence, MESH: Cough, 030212 general & internal medicine, MESH: Incidence, Child, MESH: Cohort Studies, Depression (differential diagnoses), [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Aged, education.field_of_study, MESH: France / epidemiology, MESH: Middle Aged, Incidence (epidemiology), Incidence, Cohort, General population, Middle Aged, 3. Good health, Infectious Diseases, MESH: COVID-19 / epidemiology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, France, medicine.symptom, Cohort study, Research Article, Adult, medicine.medical_specialty, Adolescent, Fever, Population, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, MESH: Fever, medicine, Humans, lcsh:RC109-216, education, MESH: Prevalence, Aged, MESH: Adolescent, MESH: Humans, business.industry, SARS-CoV-2, COVID-19, MESH: Adult, medicine.disease, MESH: Male, Cough, Risk factors, Communicable Disease Control, business, MESH: Female
Abstract

Background Our main objectives were to estimate the incidence of illnesses presumably caused by SARS-CoV-2 infection during the lockdown period and to identify the associated risk factors. Methods Participants from 3 adult cohorts in the general population in France were invited to participate in a survey on COVID-19. The main outcome was COVID-19-Like Symptoms (CLS), defined as a sudden onset of cough, fever, dyspnea, ageusia and/or anosmia, that lasted more than 3 days and occurred during the 17 days before the survey. We used delayed-entry Cox models to identify associated factors. Results Between April 2, 2020 and May 12, 2020, 279,478 participants were invited, 116,903 validated the questionnaire and 106,848 were included in the analysis. Three thousand thirty-five cases of CLS were reported during 62,099 person-months of follow-up. The cumulative incidences of CLS were 6.2% (95% Confidence Interval (95%CI): 5.7%; 6.6%) on day 15 and 8.8% (95%CI 8.3%; 9.2%) on day 45 of lockdown. The risk of CLS was lower in older age groups and higher in French regions with a high prevalence of SARS-CoV-2 infection, in participants living in cities > 100,000 inhabitants (vs rural areas), when at least one child or adolescent was living in the same household, in overweight or obese people, and in people with chronic respiratory diseases, anxiety or depression or chronic diseases other than diabetes, cancer, hypertension or cardiovascular diseases. Conclusion The incidence of CLS in the general population remained high during the first 2 weeks of lockdown, and decreased significantly thereafter. Modifiable and non-modifiable risk factors were identified.

Published
2021

20. Long-term weight change and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author

Ellingjord-Dale, Merete, Christakoudi, Sofia, Weiderpass, Elisabete, Panico, Salvatore, Dossus, Laure, Olsen, Anja, Tjonneland, Anne, Kaaks, Rudolf, Schulze, Matthias B., Masala, Giovanna, Gram, Inger T., Skeie, Guri, Rosendahl, Ann H., Sund, Malin, Key, Tim, Ferrari, Pietro, Gunter, Marc, Heath, Alicia K., Tsilidis, Konstantinos K., Riboli, Elio, Jose Sanchez, Maria, Chirlaque Lopez, Maria Dolores, Peppa, Eleni, Trichopoulou, Antonia, Martimianaki, Georgia, Agudo, Antonio, Santiuste, Carmen, Ardanaz, Eva, Amiano, Pilar, Boutron-Ruault, Marie-Christine, Simeon, Vittorio, Berrino, Franco, Tumino, Rosario, Severi, Gianluca, Stocks, Tanja, Turzanski-Fortner, Renee, Aleksandrova, Krasimira, Rylander, Charlotta, Aune, Dagfinn, Dahm, Christina C., Department of Surgery, and HUS Abdominal Center

Subjects
0301 basic medicine, Epidemiology, medicine.medical_treatment, Weight Gain, Body Mass Index, 0302 clinical medicine, Risk Factors, Prospective Studies, skin and connective tissue diseases, Public, Environmental & Occupational Health, 2. Zero hunger, Obstetrics, Hazard ratio, 0104 Statistics, Hormone replacement therapy (menopause), General Medicine, Middle Aged, EARLY ADULTHOOD, 3142 Public health care science, environmental and occupational health, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Additional Authors, long-term weight change, POSTMENOPAUSAL WOMEN, 030220 oncology & carcinogenesis, OBESITY, Obesitat, Female, medicine.symptom, Life Sciences & Biomedicine, Cohort study, Adult, medicine.medical_specialty, MENOPAUSE, Breast Neoplasms, SEX STEROIDS, Càncer de mama, 1117 Public Health and Health Services, Young Adult, 03 medical and health sciences, Breast cancer, breast cancer, BODY FATNESS, medicine, cohort study, Humans, AcademicSubjects/MED00860, VALIDITY, Science & Technology, OVERWEIGHT, business.industry, Kirurgi, Weight change, ANTHROPOMETRIC MEASURES, medicine.disease, 030104 developmental biology, Surgery, GAIN, business, Weight gain, Body mass index
Abstract

The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Kræftens Bekæmpelse) (Denmark), German Cancer Aid (Deutsche Krebshilfe), German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Federal Ministry of Education and Research (Bundesministerium fu¨ r Bildung und Forschung, BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Swedish Cancer Society (Cancerfonden), Swedish Research Council (Vetenskapsra° det), County Councils of Ska°ne and Va¨sterbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk; C570/ A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPICOxford) (UK). Infrastructure support for the Department of Epidemiology and Biostatistics at Imperial College London (UK) was provided by the NIHR Imperial Biomedical Research Centre (BRC). The funders had no role in the design and conduct of the study; the collection, analysis and interpretation of the data; or the preparation, review and approval of the manuscript; or in the decision to submit the manuscript for publication., Background: The role of obesity and weight change in breast-cancer development is complex and incompletely understood. We investigated long-term weight change and breast-cancer risk by body mass index (BMI) at age 20 years, menopausal status, hormone replacement therapy (HRT) and hormone-receptor status. Methods: Using data on weight collected at three different time points from women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the association between weight change from age 20 years until middle adulthood and risk of breast cancer. Results: In total, 150 257 women with a median age of 51 years at cohort entry were followed for an average of 14 years (standard deviation¼3.9) during which 6532 breast-cancer cases occurred. Compared with women with stable weight (62.5 kg), long-term weight gain >10 kg was positively associated with postmenopausal breast-cancer risk in women who were lean at age 20 [hazard ratio (HR)¼1.42; 95% confidence interval 1.22–1.65] in ever HRT users (HR¼1.23; 1.04–1.44), in never HRT users (HR¼1.40; 1.16–1.68) and in oestrogen-and-progesterone-receptor-positive (ERþPRþ) breast cancer (HR¼1.46; 1.15–1.85). Conclusion: Long-term weight gain was positively associated with postmenopausal breast cancer in women who were lean at age 20, both in HRT ever users and non-users, and hormone-receptor-positive breast cancer., European Commission (DG-SANCO), International Agency for Research on Cancer, Danish Cancer Society (Kraftens Bekampelse), German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council, Swedish Cancer Society, Swedish Research Council, County Councils of Skane and Vasterbotten, 14136 Cancer Research UK, C570/A16491 EPIC-Norfolk, 1000143 Medical Research Council, Infrastructure support for the Department of Epidemiology and Biostatistics at Imperial College London (UK) was provided by the NIHR Imperial Biomedical Research Centre (BRC)

Published
2021

21. Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses

Author

Khoei, Nazlisadat Seyed, Jenab, Mazda, Murphy, Neil, Banbury, Barbara L., Carreras Torres, Robert, Viallon, Vivian, Kühn, Tilman, Bueno de Mesquita, H. Bas, Aleksandrova, Krasimira, Cross, Amanda J., Weiderpass, Elisabete, Stepien, Magdalena, Bulmer, Andrew, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Carbonnel, Franck, Katzke, Verena, Boeing, Heiner, Bergmann, Manuela M., Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Merino, Susana, Bonet Bonet, Catalina, Rodríguez Barranco, Miguel, Gil, Leire, Chirlaque, María Dolores, Ardanaz, Eva, Myte, Robin, Hultdin, Johan, Pérez Cornago, Aurora, Aune, Dagfinn, Tsilidis, Konstantinos K., Albanes, Demetrius, Baron, John A., Berndt, Sonja I., Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T., Casey, Graham, Chan, Andrew T., Chang Claude, Jenny, Chanock, Stephen J., Cotterchio, Michelle, Gallinger, Steven, Gruber, Stephen B., Haile, Robert W., Hampe, Jochen, Hoffmeister, Michael, Hopper, John L., Hsu, Li, Huyghe, Jeroen R., Jenkins, Mark A., Joshi, Amit D., Kampman, Ellen, Larsson, Susanna C., Marchand, Loïc Le, Li, Christopher I., Li, Li, Lindblom, Annika, Lindor, Noralane M., Martín Sánchez, Vicente, Moreno Aguado, Víctor, Newcomb, Polly A., Offit, Kenneth, Ogino, Shuji, Parfrey, Patrick S., Pharoah, Paul D. P., Rennert, Gad, Sakoda, Lori C., Schafmayer, Clemens, Schmit, Stephanie L., Schoen, Robert E., Slattery, Martha L., Thibodeau, Stephen N., Ulrich, Cornelia M., van Duijnhoven, Franzel J. B., Weigl, Korbinian, Weinstein, Stephanie J., White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Zhang, Xuehong, Ferrari, Pietro, Anton, Gabriele, Peters, Annette, Peters, Ulrike, Gunter, Marc J., Wagner, Karl-Heinz, Freisling, Heinz, Apollo - University of Cambridge Repository, and Pharoah, Paul [0000-0001-8494-732X]

Subjects
Adult, Male, Nutrition and Disease, Mendelian randomization analysis, lcsh:Medicine, Polymorphism, Single Nucleotide, Antioxidants, Càncer colorectal, Risk Factors, Voeding en Ziekte, Humans, Prospective Studies, VLAG, Cancer, Aged, lcsh:R, Bilirubin, Middle Aged, Colorectal cancer, Europe, Case-Control Studies, Anti-oxidants, Female, Colorectal Neoplasms, Research Article
Abstract

Background: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. Methods: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10−8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study. Results: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04–1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76–0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02–1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96–1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2). Conclusions: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.

Published
2020

22. Plasma concentration of brominated flame retardants and postmenopausal breast cancer risk: A nested case-control study in the French E3N cohort

Author

Mancini, Francesca Romana, Cano-Sancho, German, Mohamed, Oceane, Cervenka, Iris, Omichessan, Hanane, Marchand, Philippe, Boutron-Ruault, Marie-Christine, Arveux, Patrick, Severi, Gianluca, Antignac, Jean-Philippe, Kvaskoff, Marina, 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), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Université de Florence, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institut National Du Cancer, INCa Mutuelle Générale de l'Education Nationale, MGEN Institut National de la Santé et de la Recherche Médicale, Inserm Institut National Du Cancer, INCa, and This work was realized with the data of the E3N cohort of the Inserm and supported by the Mutuelle G?n?rale de l'Education Nationale (MGEN), the Gustave Roussy Institute, and the French League against Cancer for the constitution and maintenance of the cohort. The work was also supported by the grant EQ. 9-C17014LS from the Cancer ITMO of the French National Alliance for Life and Health Sciences (AVIESAN), in collaboration with the Institut National du Cancer (French National Cancer Institute) and Inserm.

Subjects
lcsh:Public aspects of medicine, Research, Polybrominated Biphenyls, lcsh:RA1-1270, Breast Neoplasms, Pentabromodiphenyl ethers (PBDEs), Endocrine Disruptors, Middle Aged, Brominated flame retardants (BFRs), Polybrominated biphenyls (PBBs), Postmenopause, lcsh:RC963-969, Breast cancer, Risk Factors, Case-Control Studies, Biomonitoring, lcsh:Industrial medicine. Industrial hygiene, Halogenated Diphenyl Ethers, E3N cohort, Humans, Environmental Pollutants, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Flame Retardants
Abstract

International audience; Background: Brominated flame retardants (BFRs) are lipophilic substances with endocrine-disrupting properties. To date, only few investigations, mainly retrospective case-control studies, have explored the link between internal levels of BFRs and the risk of breast cancer, leading to conflicting results. We investigated the associations between plasma concentrations of two main groups of BFRs, PBDEs (pentabromodiphenyl ethers) and PBBs (polybrominated biphenyls), and the risk of breast cancer in a nested case-control study. Methods: A total of 197 incident breast cancer cases and 197 controls with a blood sample collected in 1994-1999 were included. Plasma levels of PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, BDE153, BDE-154) and of PBB-153 were measured by gas chromatography coupled to high-resolution mass spectrometry. Conditional logistic regression models, adjusted for potential confounders, were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Women were aged 56 years on average at blood draw. All cases, except for one, were diagnosed after menopause, with an average age at diagnosis of 68 years. Overall, we found no evidence of an association between plasma levels of PBDEs and PBB-153 and postmenopausal breast cancer risk (log-concentrations of BFRs yielding non-statistically significant ORs of 0.87 to 1.07). The analysis showed a non-linear inverse association for BDE-100 and BDE-153 and postmenopausal breast cancer risk; nevertheless, these findings were statistically significant only when the exposure was modeled as ng/L plasma (third vs. first quintile: OR = 0.42, 95%CI = 0.19-0.93 and OR = 0.42, 95%CI = 0.18-0.98, respectively) and not when modeled as ng/gr of lipids (OR = 0.58, 95%CI = 0.27-1.25 and OR = 0.53, 95%CI = 0.25-1.17). These results were unchanged in stratified analyses by tumor hormone receptor expression or body mass index. Conclusions: Our results suggest no clear association between internal levels of PBDEs and PBB-153 and the risk of breast cancer in postmenopausal women. However, these findings need to be carefully interpreted, taking into account limitations due to the limited number of women included in the study, the lack of information concerning genetic susceptibility of cases, and the unavailability of exposure assessment during critical windows of susceptibility for breast cancer. More studies are warranted to further investigate the relationships between PBDE and PBB exposure and breast cancer risk.

Published
2020

23. The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk

Author

Berger, Eloïse, Maitre, Noële, Romana Mancini, Francesca, Baglietto, Laura, Perduca, Vittorio, Colineaux, Hélène, Sieri, S., Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Boutron-Ruault, Marie Christine, Severi, Gianluca, Castagné, Raphaële, Delpierre, Cyrille, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pisa - Università di Pisa, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), CHU Toulouse [Toulouse], IRCCS Istituto Nazionale dei Tumori [Milano], University of Naples Federico II, Città della Salute e della Scienza University-Hospital, Ragusa Cancer Registry, Imperial College London, Italian Institute for Genomic Medicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Ligue Contre le Cancer SHSESP 2017–130, This work was supported by La Ligue nationale contre le cancer [Equipe Labellisée LIGUE 2017/CD]). This study has been conducted by using data from the E3N cohort that is managed by Inserm and that has been created and is maintained thanks to the support of the MGEN, the Institute Gustave Roussy and « La Ligue contre le Cancer »., This work was supported by the French National Institute of Cancer [SHSESP 2017–130 to CD]. The funder had no role in the study design, analysis and interpretation of data and in writing the manuscript., 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), and Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
Adult, Lifecourse socio-economic position, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Middle Aged, Breast cancer, Socioeconomic Factors, Risk Factors, Social mobility, Humans, Prospective cohorts, Aged, Female, Research Article
Abstract

Background Women with an advantaged socioeconomic position (SEP) have a higher risk of developing breast cancer (BC). The reasons for this association do not seem to be limited to reproductive factors and remain to be understood. We aimed to investigate the impact of lifecourse SEP from childhood and social mobility on the risk of BC considering a broad set of potential mediators. Methods We used a discovery-replication strategy in two European prospective cohorts, E3N (N = 83,436) and EPIC-Italy (N = 20,530). In E3N, 7877 women were diagnosed with BC during a median 24.4 years of follow-up, while in EPIC-Italy, 893 BC cases were diagnosed within 15.1 years. Hazard ratios (HR) were estimated using Cox proportional hazard models on imputed data. Results In E3N, women with higher education had a higher risk of BC (HR [95%CI] = 1.21 [1.12, 1.30]). This association was attenuated by adjusting for reproductive factors, in particular age at first childbirth (HR[95%CI] = 1.13 [1.04, 1.22]). Health behaviours, anthropometric variables, and BC screening had a weaker effect on the association. Women who remained in a stable advantaged SEP had a higher risk of BC (HR [95%CI] = 1.24 [1.07; 1.43]) attenuated after adjustment for potential mediators (HR [95%CI] = 1.13 [0.98; 1.31]). These results were replicated in EPIC-Italy. Conclusions These results confirm the important role of reproductive factors in the social gradient in BC risk, which does not appear to be fully explained by the large set of potential mediators, including cancer screening, suggesting that further research is needed to identify additional mechanisms. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-020-07648-w.

Published
2020

24. Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer

Author

Butt, Julia, Jenab, Mazda, Willhauck-Fleckenstein, Martina, Michel, Angelika, Pawlita, Michael, Kyrø, Cecilie, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Carbonnel, Franck, Severi, Gianluca, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Trichopoulou, Antonia, la Vecchia, Carlo, Karakatsani, Anna, Panico, Salvatore, Tumino, Rosario, Agnoli, Claudia, Palli, Domenico, Sacerdote, Carlotta, Bueno-de-Mesquita, H B As, Weiderpass, Elisabete, Sánchez, Maria-José, Bonet Bonet, Catalina, Huerta, José María, Ardanaz, Eva, Bradbury, Kathryn, Gunter, Marc, Murphy, Neil, Freisling, Heinz, Riboli, Elio, Tsilidis, Kostas, Aune, Dagfinn, Waterboer, Tim, Hughes, David J, Butt, Julia, Jenab, Mazda, Willhauck-Fleckenstein, Martina, Michel, Angelika, Pawlita, Michael, Kyrø, Cecilie, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Carbonnel, Franck, Severi, Gianluca, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Trichopoulou, Antonia, la Vecchia, Carlo, Karakatsani, Anna, Panico, Salvatore, Tumino, Rosario, Agnoli, Claudia, Palli, Domenico, Sacerdote, Carlotta, Bueno-de-Mesquita, H B A, Weiderpass, Elisabete, Sánchez, Maria-José, Bonet Bonet, Catalina, Huerta, José María, Ardanaz, Eva, Bradbury, Kathryn, Gunter, Marc, Murphy, Neil, Freisling, Heinz, Riboli, Elio, Tsilidis, Kosta, Aune, Dagfinn, Waterboer, Tim, and Hughes, David J

Subjects
Adult, Male, prospective cohort, Middle Aged, Antibodies, Bacterial, Gastrointestinal Microbiome, Streptococcus gallolyticu, antibodie, Bacterial Proteins, Case-Control Studies, Streptococcal Infections, bacterial serology, Odds Ratio, Humans, Female, Prospective Studies, colorectal neoplasm, Colorectal Neoplasms, Streptococcus gallolyticus subspecies gallolyticus, Aged
Abstract

The gut microbiome is increasingly implicated in colorectal cancer (CRC) development. A subgroup of patients diagnosed with CRC show high antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG). However, it is unclear whether the association is also present pre-diagnostically. We assessed the association of antibody responses to SGG proteins in pre-diagnostic serum samples with CRC risk in a case-control study nested within a prospective cohort. Pre-diagnostic serum samples from 485 first incident CRC cases (mean time between blood draw and diagnosis 3.4 years) and 485 matched controls in the European Prospective Investigation into Nutrition and Cancer (EPIC) study were analyzed for antibody responses to eleven SGG proteins using multiplex serology. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable conditional logistic regression models. Antibody positivity for any of the eleven SGG proteins was significantly associated with CRC risk with 56% positive controls compared to 63% positive cases (OR: 1.36, 95% CI: 1.04-1.77). Positivity for two or more proteins of a previously identified SGG 6-marker panel with greater CRC-specificity was also observed among 9% of controls compared to 17% of CRC cases, corresponding to a significantly increased CRC risk (OR: 2.17, 95% CI: 1.44-3.27). In this prospective nested case-control study we observed a positive association between antibody responses to SGG and CRC development in serum samples taken pre-diagnostically. Further work is required to establish the possibly etiological significance of these observations and whether SGG serology may be applicable for CRC risk stratification. This article is protected by copyright. All rights reserved.

Published
2018

25. Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations123

Author

Midttun, Øivind, Theofylaktopoulou, Despoina, McCann, Adrian, Fanidi, Anouar, Muller, David C, Meyer, Klaus, Ulvik, Arve, Zheng, Wei, Shu, Xiao-Ou, Xiang, Yong-Bing, Prentice, Ross, Thomson, Cynthia A, Pettinger, Mary, Giles, Graham G, Hodge, Allison, Cai, Qiuyin, Blot, William J, Wu, Jie, Johansson, Mikael, Hultdin, Johan, Grankvist, Kjell, Stevens, Victoria L, McCullough, Marjorie L, Weinstein, Stephanie J, Albanes, Demetrius, Langhammer, Arnulf, Hveem, Kristian, Næss, Marit, Sesso, Howard D, Gaziano, J Michael, Buring, Julie E, Lee, I-Min, Severi, Gianluca, Zhang, Xuehong, Han, Jiali, Stampfer, Meir J, Smith-Warner, Stephanie A, Zeleniuch-Jacquotte, Anne, le Marchand, Loic, Yuan, Jian-Min, Butler, Lesley M, Koh, Woon-Puay, Wang, Renwei, Gao, Yu-Tang, Ericson, Ulrika, Sonestedt, Emily, Ziegler, Regina G, Freedman, Neal D, Visvanathan, Kala, Jones, Miranda R, Relton, Caroline, Brennan, Paul, Johansson, Mattias, and Ueland, Per M

Subjects
Male, Asia, alpha-Tocopherol, Nutritional Status, Dietary Intake, and Body Composition, Scandinavian and Nordic Countries, Humans, Vitamin D, Vitamin A, tryptophan metabolism, Kynurenine, Aged, Lung Cancer Cohort Consortium, Australia, Tryptophan, Middle Aged, one-carbon metabolism, Carbon, United States, Cross-Sectional Studies, Dietary Supplements, Vitamin B Complex, vitamin status, biomarker, Female, Laboratories, Biomarkers
Abstract

Background: Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies. Objective: We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions. Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory. Results: Circulating concentrations of riboflavin, pyridoxal 5′-phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and α-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users. Conclusions: The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.

Published
2017

26. Circulating markers of cellular immune activation in pre-diagnostic human serum in relation to lung cancer risk in the Lung Cancer Cohort Consortium (LC3)

Author

Huang, Joyce Yongxu, Larose, Tricia L., Wang, Renwei, Fanidi, Anouar, Alcala, Karine, Stevens, Victoria L., Weinstein, Stephanie J., Albanes, Demetrius, Caporaso, Neil, Purdue, Mark, Zeigler, Regina, Freedman, Neal, Lan, Qin, Prentice, Ross, Pettinger, Mary, Thomsen, Cynthia A., Cai, Qiuyin, Wu, Jie, Blot, William J., Shu, Xiao-Ou, Zheng, Wei, Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Le Marchand, Loïc, Wilkens, Lynn R., Haiman, Christopher A., Zhang, Xuehong, Stampfer, Meir, Smith-Warner, Stephanie, Han, Jiali, Giles, Graham G, Hodge, Allison M, Severi, Gianluca, Johansson, Mikael, Grankvist, Kjell, Langhammer, Arnulf, Hveem, Kristian, Xiang, Yong-Bing, Li, Hong-Lan, Gao, Yu-Tang, Visvanathan, Kala, Bolton, Judy Hoffman, Ueland, Per M, Midttun, Øivind, Ulvik, Arve, Buring, Julie E., Lee, I-Min, Sesso, Howard D., Gaziano, J. Michael, Manjer, Jonas, Relton, Caroline, Koh, Woon-Puay, Brennan, Paul, Johansson, Mattias, and Yuan, Jian-Min

Subjects
Adult, Inflammation, Male, Lung Neoplasms, Tryptophan, Adenocarcinoma of Lung, Middle Aged, Prognosis, Neopterin, Small Cell Lung Carcinoma, Article, Risk Factors, Case-Control Studies, Biomarkers, Tumor, Carcinoma, Squamous Cell, Carcinoma, Large Cell, Humans, Female, Prospective Studies, Kynurenine, Aged, Follow-Up Studies
Abstract

Cell-mediated immunity may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), kynurenine metabolite—quinolinic acid (QA), and neopterin as markers of interferon-gamma-induced cellular immune activation with lung cancer risk in 5,364 cases and 5,364 individually matched control subjects from 20 prospective cohorts included the international Lung Cancer Cohort Consortium (LC3). Tryptophan, kynurenine, QA, and neopterin were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with different levels of these metabolites and KTR were calculated using conditional logistic regression with adjustment for matched smoking variables and circulating cotinine. Overall, the highest quintiles of circulating kynurenine, KTR, QA and neopterin were associated with a 20–30% higher risk of lung cancer, and tryptophan with a 15% lower risk compared with the lowest quintile (all P(trend)

Published
2019

27. Circulating high sensitivity C reactive protein concentrations and risk of lung cancer : nested case-control study within Lung Cancer Cohort Consortium

Author

Muller, David C, Larose, Tricia L, Hodge, Allison, Guida, Florence, Langhammer, Arnulf, Grankvist, Kjell, Meyer, Klaus, Cai, Qiuyin, Arslan, Alan A, Zeleniuch-Jacquotte, Anne, Albanes, Demetrius, Giles, Graham G, Sesso, Howard D, Lee, I-Min, Gaziano, J Michael, Yuan, Jian-Min, Hoffman Bolton, Judith, Buring, Julie E, Visvanathan, Kala, Le Marchand, Loic, Purdue, Mark P, Caporaso, Neil E, Midttun, Øivind, Ueland, Per M, Prentice, Ross L, Weinstein, Stephanie J, Stevens, Victoria L, Zheng, Wei, Blot, William J, Shu, Xiao-Ou, Zhang, Xuehong, Xiang, Yong-Bing, Koh, Woon-Puay, Hveem, Kristian, Thomson, Cynthia A, Pettinger, Mary, Engström, Gunnar, Brunnström, Hans, Milne, Roger L, Stampfer, Meir J, Han, Jiali, Johansson, Mikael, Brennan, Paul, Severi, Gianluca, and Johansson, Mattias

Subjects
Adult, Male, Lung Neoplasms, Adolescent, Risk Assessment, Sensitivity and Specificity, Young Adult, Biomarkers, Tumor, Odds Ratio, Humans, Prospective Studies, cardiovascular diseases, Carcinoma, Small Cell, Aged, Aged, 80 and over, Cancer och onkologi, Smokers, Research, Smoking, Non-Smokers, Middle Aged, C-Reactive Protein, Case-Control Studies, Cancer and Oncology, Carcinoma, Squamous Cell, Carcinoma, Large Cell, Female, Ex-Smokers, Biomarkers
Abstract

Objectives: Inflammation may play an important role in lung cancer pathogenesis. Previous studies have suggested an association between C-reactive protein (CRP) as a marker of inflammation, and risk of lung cancer, but have lacked power to comprehensively investigate associations by smoking status and histological subtype. Our objective was to conduct a comprehensive analysis of prospectively measured circulating high-sensitivity CRP (hs-CRP) concentration and risk of lung cancer overall, by smoking status (current, former and never smokers), and histological sub-type. Design: Pooled analysis of prospective case-control studies nested within 20 population cohort studies. Setting: Population-based cohort studies in the Asia, Europe, Australia, and the United States. Participants: 5299 incident lung cancer cases, with individually incidence-density matched controls. Exposure: Circulating hs-CRP concentrations in pre-diagnostic serum/plasma samples. Main Outcome Measure: Incident lung cancer diagnosis. Results: We observed a positive association between circulating hs-CRP concentration and risk of lung cancer for current (OR per doubling in hs-CRP [ORlog2CRP]: 1.09, 95% CI: 1.05 to 1.13) and former smokers (ORlog2CRP 1.09, 95% CI: 1.04 to 1.14), but not never smokers (p-interaction

Published
2019

28. Genome-wide association study of peripheral blood DNA methylation and conventional mammographic density measures

Author

Shuai, Li, Dugué, Pierre-Antoine, Baglietto, Laura, Severi, Gianluca, Wong, Ee Ming, Nguyen, Tuong L., Stone, Jennifer, English, Dallas R., Southey, Melissa C., Giles, Graham G., Hopper, John L., and Milne, Roger L.

Subjects
Adult, Cancer Research, Blood Cells, epigenetics, mammographic density, Siblings, Australia, Twins, DNA Methylation, Middle Aged, Body Mass Index, Epigenesis, Genetic, breast cancer, Oncology, DNA methylation, Case-Control Studies, Humans, Female, Aged, Breast Density, Genome-Wide Association Study, Mammography
Abstract

Age- and body mass index (BMI)-adjusted mammographic density is one of the strongest breast cancer risk factors. DNA methylation is a molecular mechanism that could underlie inter-individual variation in mammographic density. We aimed to investigate the association between breast cancer risk-predicting mammographic density measures and blood DNA methylation. For 436 women from the Australian Mammographic Density Twins and Sisters Study and 591 women from the Melbourne Collaborative Cohort Study, mammographic density (dense area, nondense area and percentage dense area) defined by the conventional brightness threshold was measured using the CUMULUS software, and peripheral blood DNA methylation was measured using the HumanMethylation450 (HM450) BeadChip assay. Associations between DNA methylation at400,000 sites and mammographic density measures adjusted for age and BMI were assessed within each cohort and pooled using fixed-effect meta-analysis. Associations with methylation at genetic loci known to be associated with mammographic density were also examined. We found no genome-wide significant (p 10

Published
2018

29. 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

30. Anthropometry and the Risk of Lung Cancer in EPIC

Author

Dewi, Nikmah Utami, Boshuizen, Hendriek C, Johansson, Mattias, Vineis, Paolo, Kampman, Ellen, Steffen, Annika, Tjønneland, Anne, Halkjær, Jytte, Overvad, Kim, Severi, Gianluca, Fagherazzi, Guy, Boutron-Ruault, Marie-Christine, Kaaks, Rudolf, Li, Kuanrong, Boeing, Heiner, Trichopoulou, Antonia, Bamia, Christina, Klinaki, Eleni, Tumino, Rosario, Palli, Domenico, Mattiello, Amalia, Tagliabue, Giovanna, Peeters, Petra H, Vermeulen, Roel, Weiderpass, Elisabete, Torhild Gram, Inger, Huerta, José María, Agudo, Antonio, Sánchez, María-José, Ardanaz, Eva, Dorronsoro, Miren, Quirós, José Ramón, Sonestedt, Emily, Johansson, Mikael, Grankvist, Kjell, Key, Tim, Khaw, Kay-Tee, Wareham, Nick, Cross, Amanda J, Norat, Teresa, Riboli, Elio, Fanidi, Anouar, Muller, David, Bueno-de-Mesquita, H Bas, 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, and Imperial College Trust

Subjects
Male, obesity, Lung Neoplasms, Nutrition and Disease, Epidemiology, Comorbidity, waist to hip ratio, ORIGINAL CONTRIBUTIONS, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 0302 clinical medicine, Waist–hip ratio, Voeding en Ziekte, Multicenter Studies as Topic, Medicine, Prospective Studies, 030212 general & internal medicine, POPULATION, Public, Environmental & Occupational Health, Human Nutrition & Health, Waist-to-height ratio, Anthropometry, Hazard ratio, Humane Voeding & Gezondheid, Confounding Factors, Epidemiologic, 11 Medical And Health Sciences, Middle Aged, waist circumference, Europe, LEANNESS, 030220 oncology & carcinogenesis, Female, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Waist, body mass index, waist-to-height ratio, Risk Assessment, smoking, 03 medical and health sciences, Journal Article, Humans, COHORT, Lung cancer, waist-to-heigh ratio, METAANALYSIS, 01 Mathematical Sciences, Aged, Proportional Hazards Models, VLAG, MODEL ANALYSIS, Science & Technology, Waist-Hip Ratio, business.industry, Proportional hazards model, CURRENT SMOKERS, Cancer, FAT DISTRIBUTION, medicine.disease, Diet, Surgery, BODY-MASS INDEX, lung cancer, business, Body mass index, Demography
Abstract

The associations of body mass index (BMI) and other anthropometric measurements with lung cancer were examined in 348,108 participants in the European Investigation Into Cancer and Nutrition (EPIC) between 1992 and 2010. The study population included 2,400 case patients with incident lung cancer, and the average length of follow-up was 11 years. Hazard ratios were calculated using Cox proportional hazard models in which we modeled smoking variables with cubic splines. Overall, there was a significant inverse association between BMI (weight (kg)/height (m)(2)) and the risk of lung cancer after adjustment for smoking and other confounders (for BMI of 30.0-34.9 versus 18.5-25.0, hazard ratio = 0.72, 95% confidence interval: 0.62, 0.84). The strength of the association declined with increasing follow-up time. Conversely, after adjustment for BMI, waist circumference and waist-to-height ratio were significantly positively associated with lung cancer risk (for the highest category of waist circumference vs. the lowest, hazard ratio = 1.25, 95% confidence interval: 1.05, 1.50). Given the decline of the inverse association between BMI and lung cancer over time, the association is likely at least partly due to weight loss resulting from preclinical lung cancer that was present at baseline. Residual confounding by smoking could also have influenced our findings.

Published
2016

31. 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

32. An International Study on the Determinants of Poor Sleep Amongst 15,000 Users of Connected Devices

Author

Fagherazzi, Guy, El Fatouhi, Douae, Bellicha, Alice, El Gareh, Amin, Affret, Aurélie, Dow, Courtney, Delrieu, Lidia, Vegreville, Matthieu, Normand, Alexis, Oppert, Jean-Michel, Severi, Gianluca, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], NOKIA Research Center, Nokia, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL UPMC, Gestionnaire, and Bellicha, Alice

Subjects
Male, Withings, Internet of Things, steps, connected devices, 0302 clinical medicine, Quality of life, Sleep Initiation and Maintenance Disorders, Epidemiology, heart rate, 030212 general & internal medicine, Slow-wave sleep, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, blood pressure, determinants, Middle Aged, 3. Good health, wearables, Nokia, Female, epidemiology, Sleep (system call), Adult, Sleep Wake Disorders, medicine.medical_specialty, lifestyle, Adolescent, Health Informatics, Wearable Electronic Devices, Young Adult, 03 medical and health sciences, Heart rate, medicine, Humans, sleep, Life Style, Simulation, Original Paper, business.industry, weight, Odds ratio, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Blood pressure, Quality of Life, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Demography
Abstract

Background: Sleep is a modifiable lifestyle factor that can be a target for efficient intervention studies to improve the quality of life and decrease the risk or burden of some chronic conditions. Knowing the profiles of individuals with poor sleep patterns is therefore a prerequisite. Wearable devices have recently opened new areas in medical research as potential efficient tools to measure lifestyle factors such as sleep quantity and quality. Objectives: The goal of our research is to identify the determinants of poor sleep based on data from a large population of users of connected devices. Methods: We analyzed data from 15,839 individuals (13,658 males and 2181 females) considered highly connected customers having purchased and used at least 3 connected devices from the consumer electronics company Withings (now Nokia). Total and deep sleep durations as well as the ratio of deep/total sleep as a proxy of sleep quality were analyzed in association with available data on age, sex, weight, heart rate, steps, and diastolic and systolic blood pressures. Results: With respect to the deep/total sleep duration ratio used as a proxy of sleep quality, we have observed that those at risk of having a poor ratio (≤0.40) were more frequently males (odds ratio [OR]female vs male=0.45, 95% CI 0.38-0.54), younger individuals (OR>60 years vs 18-30 years=0.47, 95% CI 0.35-0.63), and those with elevated heart rate (OR>78 bpm vs ≤61 bpm=1.18, 95% CI 1.04-1.34) and high systolic blood pressure (OR>133 mm Hg vs ≤116 mm Hg=1.22, 95% CI 1.04-1.43). A direct association with weight was observed for total sleep duration exclusively. Conclusions: Wearables can provide useful information to target individuals at risk of poor sleep. Future alert or mobile phone notification systems based on poor sleep determinants measured with wearables could be tested in intervention studies to evaluate the benefits. [J Med Internet Res 2017;19(10):e363]

Published
2017

33. 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

34. Impaired functional vitamin B6 status is associated with increased risk of lung cancer

Author

Theofylaktopoulou, Despoina, Midttun, Øivind, Ueland, Per M., Meyer, Klaus, Fanidi, Anouar, Zheng, Wei, Shu, Xiao Ou, Xiang, Yong Bing, Prentice, Ross, Pettinger, Mary, Thomson, Cynthia A., Giles, Graham G., Hodge, Allison, Cai, Qiuyin, Blot, William J., Wu, Jie, Johansson, Mikael, Hultdin, Johan, Grankvist, Kjell, Stevens, Victoria L., McCullough, Marjorie M., Weinstein, Stephanie J., Albanes, Demetrius, Ziegler, Regina, Freedman, Neal D., Langhammer, Arnulf, Hveem, Kristian, Næss, Marit, Sesso, Howard D., Gaziano, J. Michael, Buring, Julie E., Lee, I. Min, Severi, Gianluca, Zhang, Xuehong, Stampfer, Meir J., Han, Jiali, Smith-Warner, Stephanie A., Zeleniuch-Jacquotte, Anne, Le Marchand, Loic, Yuan, Jian Min, Wang, Renwei, Butler, Lesley M., Koh, Woon Puay, Gao, Yu Tang, Rothman, Nathaniel, Ericson, Ulrika, Sonestedt, Emily, Visvanathan, Kala, Jones, Miranda R., Relton, Caroline, Brennan, Paul, Johansson, Mattias, and Ulvik, Arve

Subjects
Male, Lung Cancer Cohort Consortium, Lung Neoplasms, pyridoxal 5′-phosphate, functional vitamin B6 marker, Middle Aged, Vitamin B 6, Article, Cohort Studies, xanthurenic acid [3-hydroxykynurenine], Risk Factors, Case-Control Studies, Carcinoma, Squamous Cell, Odds Ratio, Humans, Female, ICEP, Biomarkers, Aged
Abstract

Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5′-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case–control study consisting of 5,364 matched case–control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4th vs. 1st) was 1.25 (95% confidence interval, 1.10–1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.

Published
2017

35. Use of a Novel Nonparametric Version of DEPTH to Identify Genomic Regions Associated with Prostate Cancer Risk

Author

MacInnis, Robert J, Schmidt, Daniel F, Makalic, Enes, Severi, Gianluca, FitzGerald, Liesel M, Reumann, Matthias, Kapuscinski, Miroslaw K, Kowalczyk, Adam, Zhou, Zeyu, Goudey, Benjamin, Qian, Guoqi, Bui, Quang M, Park, Daniel J, Freeman, Adam, Southey, Melissa C, Al Olama, Ali Amin, Kote-Jarai, Zsofia, Eeles, Rosalind A, Hopper, John L, Giles, Graham G, UK Genetic Prostate Cancer Study Collaborators, Amin Al Olama, Ali [0000-0002-7178-3431], and Apollo - University of Cambridge Repository

Subjects
Machine Learning, Male, Australia, Humans, Prostatic Neoplasms, Genetic Predisposition to Disease, Middle Aged, Polymorphism, Single Nucleotide, United Kingdom, Genome-Wide Association Study
Abstract

BACKGROUND: We have developed a genome-wide association study analysis method called DEPTH (DEPendency of association on the number of Top Hits) to identify genomic regions potentially associated with disease by considering overlapping groups of contiguous markers (e.g., SNPs) across the genome. DEPTH is a machine learning algorithm for feature ranking of ultra-high dimensional datasets, built from well-established statistical tools such as bootstrapping, penalized regression, and decision trees. Unlike marginal regression, which considers each SNP individually, the key idea behind DEPTH is to rank groups of SNPs in terms of their joint strength of association with the outcome. Our aim was to compare the performance of DEPTH with that of standard logistic regression analysis. METHODS: We selected 1,854 prostate cancer cases and 1,894 controls from the UK for whom 541,129 SNPs were measured using the Illumina Infinium HumanHap550 array. Confirmation was sought using 4,152 cases and 2,874 controls, ascertained from the UK and Australia, for whom 211,155 SNPs were measured using the iCOGS Illumina Infinium array. RESULTS: From the DEPTH analysis, we identified 14 regions associated with prostate cancer risk that had been reported previously, five of which would not have been identified by conventional logistic regression. We also identified 112 novel putative susceptibility regions. CONCLUSIONS: DEPTH can reveal new risk-associated regions that would not have been identified using a conventional logistic regression analysis of individual SNPs. IMPACT: This study demonstrates that the DEPTH algorithm could identify additional genetic susceptibility regions that merit further investigation. Cancer Epidemiol Biomarkers Prev; 25(12); 1619-24. ©2016 AACR.

Published
2016
Full Text
View/download PDF

36. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer:Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

Author

Khankari, Nikhil K., Shu, Xiao Ou, Wen, Wanqing, Kraft, Peter, Lindström, Sara, Peters, Ulrike, Schildkraut, Joellen, Schumacher, Fredrick, Bofetta, Paolo, Risch, Angela, Bickeböller, Heike, Amos, Christopher I., Easton, Douglas, Eeles, Rosalind A., Gruber, Stephen B., Haiman, Christopher A., Hunter, David J., Chanock, Stephen J., Pierce, Brandon L., Zheng, Wei, Blalock, Kendra, Campbell, Peter T., Casey, Graham, Conti, David V., Edlund, Christopher K., Figueiredo, Jane, James Gauderman, W., Gong, Jian, Green, Roger C., Harju, John F., Harrison, Tabitha A., Jacobs, Eric J., Jenkins, Mark A., Jiao, Shuo, Li, Li, Lin, Yi, Manion, Frank J., Moreno, Victor, Mukherjee, Bhramar, Raskin, Leon, Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Stenzel, Stephanie L., Thomas, Duncan C., Hopper, John L., Southey, Melissa C., Makalic, Enes, Schmidt, Daniel F., Fletcher, Olivia, Peto, Julian, Gibson, Lorna, dos Santos Silva, Isabel, Ahsan, Habib, Whittemore, Alice, Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel, van der Luijt, Rob B., Uitterlinden, Andre G., Hofman, Albert, Meindl, Alfons, Schmutzler, Rita K., Müller-Myhsok, Bertram, Lichtner, Peter, Nevanlinna, Heli, Muranen, Taru A., Aittomäki, Kristiina, Blomqvist, Carl, Chang-Claude, Jenny, Hein, Rebecca, Dahmen, Norbert, Beckman, Lars, Crisponi, Laura, Hall, Per, Czene, Kamila, Irwanto, Astrid, Liu, Jianjun, Easton, Douglas F., Turnbull, Clare, Rahman, Nazneen, Eeles, Rosalind, Kote-Jarai, Zsofia, Muir, Kenneth, Giles, Graham, Neal, David, Donovan, Jenny L., Hamdy, Freddie C., Wiklund, Fredrik, Gronberg, Henrik, Haiman, Christopher, Schumacher, Fred, Travis, Ruth, Riboli, Elio, Hunter, David, Gapstur, Susan, Berndt, Sonja, Chanock, Stephen, Han, Younghun, Su, Li, Wei, Yongyue, Hung, Rayjean J., Brhane, Yonathan, McLaughlin, John, Brennan, Paul, McKay, James D., Rosenberger, Albert, Houlston, Richard S., Caporaso, Neil, Teresa Landi, Maria, Heinrich, Joachim, Wu, Xifeng, Ye, Yuanqing, Christiani, David C., Human genetics, CCA - Evaluation of Cancer Care, Eeles, Rosalind A [0000-0002-7472-5384], and Apollo - University of Cambridge Repository

Subjects
Oncology, Male, Lung Neoplasms, Social Sciences, Genome-wide association study, Biochemistry, 0302 clinical medicine, Sociology, Odds Ratio, Prospective Studies, Aged, 80 and over, Prostate Diseases, 11 Medical And Health Sciences, General Medicine, Genomics, 3. Good health, 030220 oncology & carcinogenesis, Meta-analysis, Physical Sciences, Transdisciplinary Research in Cancer of the Lung (TRICL), Medicine, DIFFERENT ANATOMIC SITES, BODY-MASS-INDEX, Statistics (Mathematics), medicine.medical_specialty, 03 medical and health sciences, Exocrine Glands, SDG 3 - Good Health and Well-being, Genome-Wide Association Studies, Genetics, Humans, Statistical Methods, Molecular Biology, RECTAL-CANCER, Aged, Science & Technology, Biology and Life Sciences, Computational Biology, Genetic Variation, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Genitourinary Tract Tumors, 030104 developmental biology, Relative risk, OLDER WOMEN, Prostate Gland, Mathematics, Meta-Analysis, Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE), 0301 basic medicine, Bioinformatics, Lung and Intrathoracic Tumors, Mathematical and Statistical Techniques, NETHERLANDS COHORT, Consortia, Risk Factors, GROWTH-FACTOR (IGF)-I, Medicine and Health Sciences, Prospective cohort study, Prostate Cancer, Middle Aged, Research Design, Female, Anatomy, Colorectal Neoplasms, Life Sciences & Biomedicine, NORWEGIAN MEN, Research Article, Biotechnology, Adult, Urology, IGF-BINDING PROTEINS, Research and Analysis Methods, Young Adult, Medicine, General & Internal, Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE), General & Internal Medicine, Internal medicine, Mendelian randomization, medicine, Journal Article, Colorectal Transdisciplinary Study (CORECT), Lung cancer, Colorectal Cancer, business.industry, Cancers and Neoplasms, Prostatic Neoplasms, JAPANESE MEN, Human Genetics, Cell Biology, Genome Analysis, Body Height, Prostate cancer, Lung and intrathoracic tumors, Prospective studies, Colorectal cancer, Prostate gland, Genome-wide association studies, FOLLOW-UP, business, Genome-Wide Association Study
Abstract

Background Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers., In a Mendelian randomisation study Pierce and colleagues show a genetic association between adult height and increased risk of colorectal and lung cancer., Author Summary Why Was This Study Done? Several previous observational studies have examined the association between adult height and risk of cancers of the lung, colon/rectum, and prostate; however, it remains unclear whether adult height is indeed related to the risk of these cancers. What Did the Researchers Do and Find? We conducted a systematic review and meta-analysis of prospective cohort studies that examined the association between adult height and the risk of colorectal, lung, and prostate cancers. To overcome inherent limitations of observational study designs, we conducted Mendelian randomization analyses using genetic data generated from a large multi-center consortium study including 47,800 cases and 81,353 controls. In the meta-analysis of the prospective observational studies, we found a 12% increased risk of colorectal cancer, a 7% increased risk of prostate cancer, and a 6% increased risk of lung cancer for every ten-centimeter increase in height, and this increased risk was corroborated in the Mendelian randomization analyses for colorectal (58%) and lung cancer (10%). What Do These Findings Mean? Our study provides strong evidence for an association between adult height and risk of colorectal and lung cancer, and suggests that certain genetic and biological factors that affect height may also affect the risk of these cancers. However, our meta-analysis was limited to published studies, and the sample size for the Mendelian randomization analysis for colorectal cancer was relatively small, affecting the precision of the risk estimate.

Published
2016

37. A meta-analysis of individual participant data reveals an association between circulating levels of IGF-I and prostate cancer risk

Author

Travis, Ruth, Appleby, Paul, Martin, Richard, Holly, Jeff M.P., Albanes, Demetrius, Black, Amanda, Bueno-De-Mesquita, H. Bas, Chan, June, Chen, Chu, Chirlaque, María-Dolores, Cook, Michael, Deschasaux, Mélanie, Donovan, Jenny, Ferrucci, Luigi, Galan, Pilar, Giles, Graham, Giovannucci, Edward, Gunter, Marc, Habel, Laurel, Hamdy, Freddie, Helzlsouer, Kathy, Hercberg, Serge, Hoover, Robert, Janssen, Joseph A.M.J.L., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loïc, Metter, E. Jeffrey, Mikami, Kazuya, Morris, Joan, Neal, David, Neuhouser, Marian, Ozasa, Kotaro, Palli, Domenico, Platz, Elizabeth, Pollak, Michael, Price, Alison, Roobol, Monique, Schaefer, Catherine, Schenk, Jeannette, Severi, Gianluca, Stampfer, Meir, Stattin, Pär, Tamakoshi, Akiko, Tangen, Catherine, Touvier, Mathilde, Wald, Nicholas, Weiss, Noel, Ziegler, Regina, Key, Timothy, Allen, Naomi, Nuffield Department of Population Health [Oxford], University of Oxford [Oxford], School of Social and Community Medicine [Bristol], University of Bristol [Bristol], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of California [San Francisco] (UCSF), University of California, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institute on Aging [Bethesda, USA] (NIA), University of Melbourne, Harvard School of Public Health, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Kaiser Permanente, Nuffield (Nuffield), Mercy Medical Center, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Occupational and Environmental Health [Kitakyushu] (UEOH), University of Hawai‘i [Mānoa] (UHM), Kyoto Prefectural University of Medicine [Kyoto, Japon], Queen Mary University of London (QMUL), University of Cambridge [UK] (CAM), Radiation Effects Research Foundation, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Cancer Prevention Research Unit, Department of Oncology, McGill University = Université McGill [Montréal, Canada]-Jewish General Hospital, University of Washington [Seattle], Cancer Epidemiology Centre, Cancer Council Victoria, Human Genetics Foundation (HuGeF), Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Hokkaido University Hospital [Sapporo], University of Oxford, University of California [San Francisco] (UC San Francisco), University of California (UC), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and Deschasaux-Tanguy, Mélanie

Subjects
Urologic Diseases, Male, Aging, Oncology and Carcinogenesis, Article, growth-factor-i, serum-insulin, Risk Factors, prevention trial, Humans, Oncology & Carcinogenesis, Insulin-Like Growth Factor I, factor axis, igfbp-3, Cancer, Aged, Prostate Cancer, hyperplasia, Prostatic Neoplasms, Middle Aged, susceptibility loci, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, factor-binding protein-2, Centre for Surgical Research, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, factor (igf)-i, diet, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. Aftermutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development.

Published
2016

38. Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies

Author

Key, Timothy J, Appleby, Paul N, Travis, Ruth C, Albanes, Demetrius, Alberg, Anthony J, Barricarte, Aurelio, Black, Amanda, Boeing, Heiner, Bueno-de-Mesquita, H Bas, Chan, June M, Chen, Chu, Cook, Michael B, Donovan, Jenny L, Galan, Pilar, Gilbert, Rebecca, Giles, Graham G, Giovannucci, Edward, Goodman, Gary E, Goodman, Phyllis J, Gunter, Marc J, Hamdy, Freddie C, Heliövaara, Markku, Helzlsouer, Kathy J, Henderson, Brian E, Hercberg, Serge, Hoffman-Bolton, Judy, Hoover, Robert N, Johansson, Mattias, Khaw, Kay-Tee, King, Irena B, Knekt, Paul, Kolonel, Laurence N, Le Marchand, Loic, Männistö, Satu, Martin, Richard M, Meyer, Haakon E, Mondul, Alison M, Moy, Kristin A, Neal, David E, Neuhouser, Marian L, Palli, Domenico, Platz, Elizabeth A, Pouchieu, Camille, Rissanen, Harri, Schenk, Jeannette M, Severi, Gianluca, Stampfer, Meir J, Tjønneland, Anne, Touvier, Mathilde, Trichopoulou, Antonia, Weinstein, Stephanie J, Ziegler, Regina G, Zhou, Cindy Ke, Allen, Naomi E, and Endogenous Hormones Nutritional Biomarkers Prostate Cancer Collaborative Group

Subjects
Adult, Male, Urologic Diseases, Aging, alpha-Tocopherol, vitamin E, Medical and Health Sciences, vitamin A, Cohort Studies, Lycopene, Engineering, Meta-Analysis as Topic, nested case-control study, Risk Factors, Clinical Research, Humans, Prospective Studies, Neoplasm Staging, Cancer, Nutrition, Endogenous Hormones Nutritional Biomarkers Prostate Cancer Collaborative Group, Nutrition & Dietetics, Prostate Cancer, Prevention, Prostate, carotenoids, Prostatic Neoplasms, biomarkers, Middle Aged, Observational Studies as Topic, Cross-Sectional Studies, Case-Control Studies, Neoplasm Grading, pooled analysis, tocopherols, retinol
Abstract

BackgroundIndividual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.ObjectiveThe objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, α-tocopherol, and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors.DesignPrincipal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets.ResultsData were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For α-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). γ-Tocopherol was not associated with risk.ConclusionsOverall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol. Whether these associations reflect causal relations is unclear.

Published
2015

39. 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

40. 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

41. Common non-synonymous snps associated with breast cancer susceptibility: findings from the breast cancer association consortium

Author

Milne, Roger L., Burwinkel, Barbara, Michailidou, Kyriaki, Arias-Perez, Jose-Ignacio, Zamora, M. Pilar, Menéndez-Rodríguez, Primitiva, Hardisson, David, Mendiola, Marta, González-Neira, Anna, Pita, Guillermo, Alonso, M. Rosario, Dennis, Joe, Wang, Qin, Bolla, Manjeet K., Swerdlow, Anthony, Ashworth, Alan, Orr, Nick, Schoemaker, Minouk, Ko, Yon-Dschun, Brauch, Hiltrud, Hamann, Ute, Andrulis, Irene L., Knight, Julia A., Glendon, Gord, Tchatchou, Sandrine, Matsuo, Keitaro, Ito, Hidemi, Iwata, Hiroji, Tajima, Kazuo, Li, Jingmei, Brand, Judith S., Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volker, Stegmaier, Christa, Lambrechts, Diether, Peuteman, Gilian, Christiaens, Marie-Rose, Smeets, Ann, Jakubowska, Anna, Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katazyna, Hartman, Mikael, Hui, Miao, Yen Lim, Wei, Wan Chan, Ching, Marme, Federick, Yang, Rongxi, Bugert, Peter, Lindblom, Annika, Margolin, Sara, García-Closas, Montserrat, Chanock, Stephen J., Lissowska, Jolanta, Figueroa, Jonine D., Bojesen, Stig E., Nordestgaard, Børge G., Flyger, Henrik, Hooning, Maartje J., Kriege, Mieke, van den Ouweland, Ans M.W., Koppert, Linetta B., Fletcher, Olivia, Johnson, Nichola, dos-Santos-Silva, Isabel, Peto, Julian, Zheng, Wei, Deming-Halverson, Sandra, Shrubsole, Martha J., Long, Jirong, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Cox, Angela, Cross, Simon S., Reed, Malcolm W.R., Schmidt, Marjanka K., Broeks, Annegien, Cornelissen, Sten, Braaf, Linde, Kang, Daehee, Choi, Ji-Yeob, Park, Sue K., Noh, Dong-Young, Simard, Jacques, Dumont, Martine, Goldberg, Mark S., Labrèche, France, Fasching, Peter A., Hein, Alexander, Ekici, Arif B., Beckmann, Matthias W., Radice, Paolo, Peterlongo, Paolo, Azzollini, Jacopo, Barile, Monica, Sawyer, Elinor, Tomlinson, Ian, Kerin, Michael, Miller, Nicola, Hopper, John L., Schmidt, Daniel F., Makalic, Enes, Southey, Melissa C., Hwang Teo, Soo, Har Yip, Cheng, Sivanandan, Kavitta, Tay, Wan-Ting, Shen, Chen-Yang, Hsiung, Chia-Ni, Yu, Jyh-Cherng, Hou, Ming-Feng, Guénel, Pascal, Truong, Therese, Sanchez, Marie, Mulot, Claire, Blot, William, Cai, Qiuyin, Nevanlinna, Heli, Muranen, Taru A., Aittomäki, Kristiina, Blomqvist, Carl, Wu, Anna H., Tseng, Chiu-Chen, Van Den Berg, David, Stram, Daniel O., Bogdanova, Natalia, Dörk, Thilo, Muir, Kenneth, Lophatananon, Artitaya, Stewart-Brown, Sarah, Siriwanarangsan, Pornthep, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Shu, Xiao-Ou, Lu, Wei, Gao, Yu-Tang, Zhang, Ben, Couch, Fergus J., Toland, Amanda E., Yannoukakos, Drakoulis, Sangrajrang, Suleeporn, McKay, James, Wang, Xianshu, Olson, Janet E., Vachon, Celine, Purrington, Kristen, Severi, Gianluca, Baglietto, Laura, Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick, Le Marchand, Loic, Devilee, Peter, Tollenaar, Robert A.E.M., Seynaeve, Caroline, Czene, Kamila, Eriksson, Mikael, Humphreys, Keith, Darabi, Hatef, Ahmed, Shahana, Shah, Mitul, Pharoah, Paul D.P., Hall, Per, Giles, Graham G., Benítez, Javier, Dunning, Alison M., Chenevix-Trench, Georgia, Easton, Douglas F., Berchuck, Andrew, Eeles, Rosalind A., Olama, Ali Amin Al, Kote-Jarai, Zsofia, Benlloch, Sara, Antoniou, Antonis, McGuffog, Lesley, Offit, Ken, Lee, Andrew, Dicks, Ed, Luccarini, Craig, Tessier, Daniel C., Bacot, Francois, Vincent, Daniel, LaBoissière, Sylvie, Robidoux, Frederic, Nielsen, Sune F., Cunningham, Julie M., Windebank, Sharon A., Hilker, Christopher A., Meyer, Jeffrey, Angelakos, Maggie, Maskiell, Judi, van der Schoot, Ellen, Rutgers, Emiel, Verhoef, Senno, Hogervorst, Frans, Boonyawongviroj, Prat, Siriwanarungsan, Pornthep, Schrauder, Michael, Rübner, Matthias, Oeser, Sonja, Landrith, Silke, Williams, Eileen, Ryder-Mills, Elaine, Sargus, Kara, McInerney, Niall, Colleran, Gabrielle, Rowan, Andrew, Jones, Angela, Sohn, Christof, Schneeweiß, Andeas, Álvarez, Núria, Lacey, James, Wang, Sophia, Ma, Huiyan, Lu, Yani, Deapen, Dennis, Pinder, Rich, Lee, Eunjung, Schumacher, Fred, Horn-Ross, Pam, Reynolds, Peggy, Nelson, David, Ziegler, Hartwig, Wolf, Sonja, Hermann, Volker, Lo, Wing-Yee, Justenhoven, Christina, Baisch, Christian, Fischer, Hans-Peter, Brüning, Thomas, Pesch, Beate, Rabstein, Sylvia, Lotz, Anne, Harth, Volker, Heikkinen, Tuomas, Erkkilä, Irja, Aaltonen, Kirsimari, von Smitten, Karl, Antonenkova, Natalia, Hillemanns, Peter, Christiansen, Hans, Myöhänen, Eija, Kemiläinen, Helena, Thorne, Heather, Niedermayr, Eveline, Bowtell, D, Chenevix-Trench, G, deFazio, A, Gertig, D, Green, A, Webb, P, Green, A., Parsons, P., Hayward, N., Webb, P., Whiteman, D., Fung, Annie, Yashiki, June, Smeets, Dominiek, Brussel, Thomas Van, Corthouts, Kathleen, Obi, Nadia, Heinz, Judith, Behrens, Sabine, Eilber, Ursula, Celik, Muhabbet, Olchers, Til, Manoukian, Siranoush, Peissel, Bernard, Scuvera, Giulietta, Zaffaroni, Daniela, Bonanni, Bernardo, Feroce, Irene, Maniscalco, Angela, Rossi, Alessandra, Bernard, Loris, Tranchant, Martine, Valois, Marie-France, Turgeon, Annie, Heguy, Lea, Sze Yee, Phuah, Kang, Peter, Nee, Kang In, Mariapun, Shivaani, Sook-Yee, Yoon, Lee, Daphne, Ching, Teh Yew, Taib, Nur Aishah Mohd, Otsukka, Meeri, Mononen, Kari, Selander, Teresa, Weerasooriya, Nayana, staff, OFBCR, Krol-Warmerdam, E., Molenaar, J., Blom, J., Brinton, Louise, Szeszenia-Dabrowska, Neonila, Peplonska, Beata, Zatonski, Witold, Chao, Pei, Stagner, Michael, Bos, Petra, Blom, Jannet, Crepin, Ellen, Nieuwlaat, Anja, Heemskerk, Annette, Higham, Sue, Cross, Simon, Cramp, Helen, Connley, Dan, Balasubramanian, Sabapathy, Brock, Ian, Conroy, Don, Baynes, Caroline, and Chua, Kimberley

Subjects
Adult, A Kinase Anchor Proteins, Alleles, Ataxin-7, Breast Neoplasms, Case-Control Studies, Cytoskeletal Proteins, Female, Genome-Wide Association Study, Humans, Middle Aged, Nerve Tissue Proteins, Protein-Serine-Threonine Kinases, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Molecular Biology, Genetics, Genetics (clinical), Protein Serine-Threonine Kinases, Medizinische Fakultät, NIMA-Related Kinases, ddc:610, Polymorphism, risk, variants, Association Studies Articles, identifies 2, Single Nucleotide, confer susceptibility, 5p12, loci, alleles, genome-wide association, metaanalysis
Abstract

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.

Published
2014

42. Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer

Author

Purrington, Kristen S, Slager, Susan, Eccles, Diana, Yannoukakos, Drakoulis, Fasching, Peter A, Miron, Penelope, Carpenter, Jane, Chang-Claude, Jenny, Martin, Nicholas G, Montgomery, Grant W, Kristensen, Vessela, Anton-Culver, Hoda, Goodfellow, Paul, Tapper, William J, Rafiq, Sajjad, Gerty, Susan M, Durcan, Lorraine, Konstantopoulou, Irene, Fostira, Florentia, Vratimos, Athanassios, Apostolou, Paraskevi, Konstanta, Irene, Kotoula, Vassiliki, Lakis, Sotiris, Dimopoulos, Meletios A, Skarlos, Dimosthenis, Pectasides, Dimitrios, Fountzilas, George, Beckmann, Matthias W, Hein, Alexander, Ruebner, Matthias, Ekici, Arif B, Hartmann, Arndt, Schulz-Wendtland, Ruediger, Renner, Stefan P, Janni, Wolfgang, Rack, Brigitte, Scholz, Christoph, Neugebauer, Julia, Andergassen, Ulrich, Lux, Michael P, Haeberle, Lothar, Clarke, Christine, Pathmanathan, Nirmala, Rudolph, Anja, Flesch-Janys, Dieter, Nickels, Stefan, Olson, Janet E, Ingle, James N, Olswold, Curtis, Slettedahl, Seth, Eckel-Passow, Jeanette E, Anderson, S Keith, Visscher, Daniel W, Cafourek, Victoria L, Sicotte, Hugues, Prodduturi, Naresh, Weiderpass, Elisabete, Bernstein, Leslie, Ziogas, Argyrios, Ivanovich, Jennifer, Giles, Graham G, Baglietto, Laura, Southey, Melissa, Kosma, Veli-Matti, Fischer, Hans-Peter, GENICA Network, Reed, Malcom WR, Cross, Simon S, Deming-Halverson, Sandra, Shrubsole, Martha, Cai, Qiuyin, Shu, Xiao-Ou, Daly, Mary, Weaver, Joellen, Ross, Eric, Klemp, Jennifer, Sharma, Priyanka, Torres, Diana, Rüdiger, Thomas, Wölfing, Heidrun, Ulmer, Hans-Ulrich, Försti, Asta, Khoury, Thaer, Kumar, Shicha, Pilarski, Robert, Shapiro, Charles L, Greco, Dario, Heikkilä, Päivi, Aittomäki, Kristiina, Blomqvist, Carl, Irwanto, Astrid, Liu, Jianjun, Pankratz, Vernon Shane, Wang, Xianshu, Severi, Gianluca, Mannermaa, Arto, Easton, Douglas, Hall, Per, Brauch, Hiltrud, Cox, Angela, Zheng, Wei, Godwin, Andrew K, Hamann, Ute, Ambrosone, Christine, Toland, Amanda Ewart, Nevanlinna, Heli, Vachon, Celine M, and Couch, Fergus J

Subjects
Adult, Aged, 80 and over, Quantitative Trait Loci, Oncology and Carcinogenesis, Estrogen Receptor alpha, Triple Negative Breast Neoplasms, Middle Aged, Polymorphism, Single Nucleotide, Young Adult, Case-Control Studies, Humans, Genetic Predisposition to Disease, Female, Oncology & Carcinogenesis, GENICA Network, Chromosomes, Human, Pair 19, Aged, Genome-Wide Association Study
Abstract

Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.

Published
2014

43. Anthropometric measures and bladder cancer risk: a prospective study in the EPIC cohort

Author

Roswall, Nina, Freisling, Heinz, Bueno-de-Mesquita, H B As, Ros, Martine, Christensen, Jane, Overvad, Kim, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Fagherazzi, Guy, Chang-Claude, Jenny, Kaaks, Rudolf, Steffen, Annika, Boeing, Heiner, Argüelles, Marcial, Agudo, Antonio, Sánchez, María-José, Chirlaque, Maria-Dolores, Gurrea, Aurelio Barricarte, Amiano, Pilar, Wareham, Nick, Khaw, Kay-Tee, Bradbury, Kathryn Erica, Trichopoulou, Antonia, Papatesta, Helen-Maria, Trichopoulos, Dimitrios, Palli, Domenico, Pala, Valeria, Tumino, Rosario, Sacerdote, Carlotta, Mattiello, Amalia, Peeters, Petra H, Ehrnström, Roy, Brennan, Paul, Ferrari, Pietro, Ljungberg, Börje, Norat, Teresa, Gunter, Marc, Riboli, Elio, Weiderpass, Elisabete, and Halkjaer, Jytte

Subjects
Adult, Aged, 80 and over, Male, Anthropometry, Waist-Hip Ratio, Smoking, Middle Aged, Body Mass Index, Young Adult, Urinary Bladder Neoplasms, Risk Factors, Humans, Female, Obesity, Prospective Studies, Waist Circumference, Aged, Proportional Hazards Models
Abstract

Anthropometric measures have been related to risk of several cancers. For bladder cancer, however, evidence is sparse. Comparability of existing studies is hampered by use of different obesity-measures, inadequate control for smoking, and few female cases. This study examined associations between height, weight, waist and hip circumference, waist-hip-ratio, waist-height-ratio, BMI, recalled weight at age 20 and bladder cancer, and investigated effect modification by age, tumor aggressiveness and smoking. The study was conducted in the European Prospective Investigation into Cancer and Nutrition cohort, in 390,878 participants. Associations were calculated using Cox Proportional Hazards Models. During follow-up, 1,391 bladder cancers (1,018 male; 373 female) occurred. Height was unrelated to bladder cancer in both genders. We found a small but significant positive association with weight (1.04 (1.01-1.07) per 5 kilo), BMI (1.05 (1.02-1.08) per 2 units), waist circumference (1.04 (1.01-1.08) per 5 cm), waist-hip-ratio (1.07 (1.02-1.13) per 0.05 unit) and waist-height ratio (1.07 (1.01-1.13) per 0.05 unit) in men. Stratification by smoking status confined associations in men to former smokers. In never smokers, we found no significant associations, suggesting residual confounding by smoking. Results did not differ with tumor aggressiveness and age. Residual analyses on BMI/waist circumference showed a significantly higher disease risk with BMI in men (p = 0.01), but no association with waist circumference. In conclusion, in this large study, height was unrelated to bladder cancer, whereas overweight was associated with a slightly higher bladder cancer risk in men. This association may, however, be distorted by residual confounding by smoking. © 2014 Wiley Periodicals, Inc.

Published
2014

44. 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

45. Dynamics of smoking-induced genome-wide methylation changes with time since smoking cessation

Author

Guida, Florence, Sandanger, Torkjel M, Castagné, Raphaële, Campanella, Gianluca, Polidoro, Silvia, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Sacerdote, Carlotta, Panico, Salvatore, Severi, Gianluca, Kyrtopoulos, Soterios A, Georgiadis, Panagiotis, Vermeulen, Roel C H, Lund, Eiliv, Vineis, Paolo, Chadeau-Hyam, Marc, Risk Assessment, Infection & Immunity, dIRAS RA-I&I RA, LS IRAS EEPI GRA (Gezh.risico-analyse), Guida, Florence, Sandanger, Torkjel M, Castagné, Raphaële, Campanella, Gianluca, Polidoro, Silvia, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Sacerdote, Carlotta, Panico, Salvatore, Severi, Gianluca, Kyrtopoulos, Soterios A, Georgiadis, Panagioti, Vermeulen, Roel C. H, Lund, Eiliv, Vineis, Paolo, Chadeau Hyam, Marc, Risk Assessment, Infection & Immunity, dIRAS RA-I&I RA, and LS IRAS EEPI GRA (Gezh.risico-analyse)

Subjects
Adult, Male, Time Factors, Time Factor, medicine.medical_treatment, Biology, Bioinformatics, Epigenesis, Genetic, Genetics, medicine, Humans, Epigenetics, Lung cancer, Molecular Biology, Genetics (clinical), Genetic association, Aged, Genome, Human, Smoking, Case-control study, General Medicine, Methylation, Articles, DNA Methylation, Middle Aged, medicine.disease, CpG site, Case-Control Studies, DNA methylation, Smoking cessation, CpG Islands, Female, Smoking Cessation, Case-Control Studie, CpG Island, Human
Abstract

Several studies have recently identified strong epigenetic signals related to tobacco smoking. However, an aspect that did not receive much attention is the evolution of epigenetic changes with time since smoking cessation. We conducted a series of epigenome-wide association studies to capture the dynamics of smoking-induced epigenetic changes after smoking cessation, using genome-wide methylation profiles obtained from blood samples in 745 women from 2 European populations. Two distinct classes of CpG sites were identified: sites whose methylation reverts to levels typical of never smokers within decades after smoking cessation, and sites remaining differentially methylated, even more than 35 years after smoking cessation. Our results suggest that the dynamics of methylation changes following smoking cessation are driven by a differential and site-specific magnitude of the smoking-induced alterations (with persistent sites being most affected) irrespective of the intensity and duration of smoking. Analyses of the link between methylation and expression levels revealed that methylation predominantly and remotely down-regulates gene expression. Among genes whose expression was associated with our candidate CpG sites, LRRN3 appeared to be particularly interesting as it was one of the few genes whose methylation and expression were directly associated, and the only gene in which both methylation and gene expression were found associated with smoking. Our study highlights persistent epigenetic markers of smoking, which can potentially be detected decades after cessation. Such historical signatures are promising biomarkers to refine individual risk profiling of smoking-induced chronic disease such as lung cancer.

Published
2015

46. Genetic predisposition to in situ and invasive lobular carcinoma of the breast

Author

Sawyer, Elinor, Roylance, Rebecca, Petridis, Christos, Brook, Mark N, Nowinski, Salpie, Papouli, Efterpi, Fletcher, Olivia, Pinder, Sarah, Hanby, Andrew, Kohut, Kelly, Gorman, Patricia, Caneppele, Michele, Peto, Julian, Dos Santos Silva, Isabel, Johnson, Nichola, Swann, Ruth, Dwek, Miriam, Perkins, Katherine-Anne, Gillett, Cheryl, Houlston, Richard, Ross, Gillian, De Ieso, Paolo, Southey, Melissa C, Hopper, John L, Provenzano, Elena, Apicella, Carmel, Wesseling, Jelle, Cornelissen, Sten, Keeman, Renske, Fasching, Peter A, Jud, Sebastian M, Ekici, Arif B, Beckmann, Matthias W, Kerin, Michael J, Marme, Federick, Schneeweiss, Andreas, Sohn, Christof, Burwinkel, Barbara, Guénel, Pascal, Truong, Therese, Laurent-Puig, Pierre, Kerbrat, Pierre, Bojesen, Stig E, Nordestgaard, Børge G, Nielsen, Sune F, Flyger, Henrik, Milne, Roger L, Perez, Jose Ignacio Arias, Menéndez, Primitiva, Benitez, Javier, Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volker, Stegmaier, Christa, Meindl, Alfons, Lichtner, Peter, Schmutzler, Rita K, Lochmann, Magdalena, Brauch, Hiltrud, Fischer, Hans-Peter, Ko, Yon-Dschun, GENICA Network, Nevanlinna, Heli, Muranen, Taru A, Aittomäki, Kristiina, Blomqvist, Carl, Bogdanova, Natalia V, Dörk, Thilo, Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M, Chenevix-Trench, Georgia, KConFab Investigators, Lambrechts, Diether, Weltens, Caroline, Van Limbergen, Erik, Hatse, Sigrid, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Radice, Paolo, Peterlongo, Paolo, Bonanni, Bernardo, Volorio, Sara, Giles, Graham G, Severi, Gianluca, Baglietto, Laura, McLean, Catriona A, Haiman, Christopher A, Henderson, Brian E, Schumacher, Fredrick, Le Marchand, Loic, Simard, Jacques, Goldberg, Mark S, Labrèche, France, Dumont, Martine, Kristensen, Vessela, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Kauppila, Saila, Andrulis, Irene L, Knight, Julia A, Glendon, Gord, Mulligan, Anna Marie, Devillee, Peter, Tollenaar, Rob AEM, Seynaeve, Caroline M, Kriege, Mieke, Figueroa, Jonine, Chanock, Stephen J, Sherman, Mark E, Hooning, Maartje J, Hollestelle, Antoinette, Van Den Ouweland, Ans MW, Van Deurzen, Carolien HM, Li, Jingmei, Czene, Kamila, Humphreys, Keith, Cox, Angela, Cross, Simon S, Reed, Malcolm WR, Shah, Mitul, Jakubowska, Anna, Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Swerdlow, Anthony, Ashworth, Alan, Orr, Nicholas, Schoemaker, Minouk, Couch, Fergus J, Hallberg, Emily, González-Neira, Anna, Pita, Guillermo, Alonso, M Rosario, Tessier, Daniel C, Vincent, Daniel, Bacot, Francois, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Michailidou, Kyriaki, Dunning, Alison M, Hall, Per, Easton, Doug, Pharoah, Paul, Schmidt, Marjanka K, Tomlinson, Ian, and Garcia-Closas, Montserrat

Subjects
Genotype, Breast Neoplasms, Middle Aged, Polymorphism, Single Nucleotide, 3. Good health, body regions, Carcinoma, Lobular, Case-Control Studies, Humans, Female, Genetic Predisposition to Disease, skin and connective tissue diseases, Carcinoma in Situ, Genome-Wide Association Study
Abstract

Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P

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

Author

Rolandsson, Olov, Hampe, Christiane S, Sharp, Stephen J, Ardanaz, Eva, Boeing, Heiner, Fagherazzi, Guy, Mancini, Francesca Romana, Nilsson, Peter M, Overvad, Kim, Chirlaque, Maria-Dolores, Dorronsoro, Miren, Gunter, Marc J, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay-Tee, Krogh, Vittorio, Kühn, Tilman, Palli, Domenico, Panico, Salvatore, Sacerdote, Carlotta, Sánchez, Maria-José, Severi, Gianluca, Spijkerman, Annemieke MW, Tumino, Rosario, Van Der Schouw, Yvonne T, Riboli, Elio, Forouhi, Nita G, Langenberg, Claudia, and Wareham, Nicholas J

Subjects
Adult, Male, Glutamate Decarboxylase, Autoimmunity, Type 2 diabetes, Middle Aged, Genetic risk score, Antibodies, 3. Good health, Autoantibody, Type 1 diabetes, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Incident diabetes, Case-Control Studies, Humans, Female, Aged
Abstract

AIMS/HYPOTHESIS: Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. METHODS: GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. RESULTS: GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. CONCLUSIONS/INTERPRETATION: Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.

48. Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models: results from the EPIC cohort

Author

Fortner, Renée T, Vitonis, Allison F, Schock, Helena, Hüsing, Anika, Johnson, Theron, 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, Benetou, Vassiliki, La Vecchia, Carlo, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Matullo, Giuseppe, Mattiello, Amalia, Onland-Moret, N Charlotte, Peeters, Petra H, Weiderpass, Elisabete, Gram, Inger Torhild, Jareid, Mie, Quirós, J Ramón, Duell, Eric J, Sánchez, Maria-Jose, Chirlaque, María Dolores, Ardanaz, Eva, Larrañaga, Nerea, Nodin, Björn, Brändstedt, Jenny, Idahl, Annika, Khaw, Kay-Tee, Allen, Naomi, Gunter, Marc, Johansson, Mattias, Dossus, Laure, Merritt, Melissa A, Riboli, Elio, Cramer, Daniel W, Kaaks, Rudolf, and Terry, Kathryn L

Subjects
Adult, Ovarian Neoplasms, CA15.3, HE4, Middle Aged, 3. Good health, Cohort Studies, Europe, CA125, Cross-Sectional Studies, Ovarian cancer, Risk Factors, Area Under Curve, Case-Control Studies, Population Surveillance, Early detection markers, Biomarkers, Tumor, Humans, Female, Early Detection of Cancer, Aged
Abstract

BACKGROUND: Ovarian cancer early detection markers CA125, CA15.3, HE4, and CA72.4 vary between healthy women, limiting their utility for screening. METHODS: We evaluated cross-sectional relationships between lifestyle and reproductive factors and these markers among controls (n = 1910) from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Improvements in discrimination of prediction models adjusting for correlates of the markers were evaluated among postmenopausal women in the nested case-control study (n = 590 cases). Generalized linear models were used to calculate geometric means of CA125, CA15.3, and HE4. CA72.4 above vs. below limit of detection was evaluated using logistic regression. Early detection prediction was modeled using conditional logistic regression. RESULTS: CA125 concentrations were lower, and CA15.3 higher, in post- vs. premenopausal women (p ≤ 0.02). Among postmenopausal women, CA125 was higher among women with higher parity and older age at menopause (ptrend ≤ 0.02), but lower among women reporting oophorectomy, hysterectomy, ever use of estrogen-only hormone therapy, or current smoking (p < 0.01). CA15.3 concentrations were higher among heavier women and in former smokers (p ≤ 0.03). HE4 was higher with older age at blood collection and in current smokers, and inversely associated with OC use duration, parity, and older age at menopause (≤ 0.02). No associations were observed with CA72.4. Adjusting for correlates of the markers in prediction models did not improve the discrimination. CONCLUSIONS: This study provides insights into sources of variation in ovarian cancer early detection markers in healthy women and informs about the utility of individualizing marker cutpoints based on epidemiologic factors.

49. Mitochondrial DNA Copy-Number Variation and Pancreatic Cancer Risk in the Prospective EPIC Cohort

Author

Gentiluomo, Manuel, Katzke, Verena A, Kaaks, Rudolf, Tjønneland, Anne, Severi, Gianluca, Perduca, Vittorio, Boutron-Ruault, Marie-Christine, Weiderpass, Elisabete, Ferrari, Pietro, Johnson, Theron, Schulze, Matthias B, Bergmann, Manuela, Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Palli, Domenico, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-De-Mesquita, Bas, Vermeulen, Roel, Sandanger, Torkjel M, Quirós, J Ramón, Rodriguez-Barranco, Miguel, Amiano, Pilar, Colorado-Yohar, Sandra, Ardanaz, Eva, Sund, Malin, Khaw, Kay-Tee, Wareham, Nicholas J, Schmidt, Julie A, Jakszyn, Paula, Morelli, Luca, Canzian, Federico, and Campa, Daniele

Subjects
2. Zero hunger, Adult, Male, DNA Copy Number Variations, Incidence, Age Factors, Middle Aged, Protective Factors, Real-Time Polymerase Chain Reaction, DNA, Mitochondrial, Risk Assessment, 3. Good health, Mitochondria, Europe, Pancreatic Neoplasms, Risk Factors, Case-Control Studies, Biomarkers, Tumor, Leukocytes, Humans, Female, Prospective Studies, Aged
Abstract

BACKGROUND: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited. METHODS: To further our knowledge on this topic, we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. RESULTS: We observed lower mtDNA copy number with advancing age (P = 6.54 × 10-5) and with a high body mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.16-0.79; P = 0.01] when comparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 (95% CI, 0.07-0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses. CONCLUSIONS: Our results suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk. IMPACT: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer.

50. The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium

Author

Guida, Florence, Tan, Vanessa Y, Corbin, Laura J, Smith-Byrne, Karl, Alcala, Karine, Langenberg, Claudia, Stewart, Isobel D, Butterworth, Adam S, Surendran, Praveen, Achaintre, David, Adamski, Jerzy, Amiano Exezarreta, Pilar, Bergmann, Manuela M, Bull, Caroline J, Dahm, Christina C, Gicquiau, Audrey, Giles, Graham G, Gunter, Marc J, Haller, Toomas, Langhammer, Arnulf, Larose, Tricia L, Ljungberg, Börje, Metspalu, Andres, Milne, Roger L, Muller, David C, Nøst, Therese H, Pettersen Sørgjerd, Elin, Prehn, Cornelia, Riboli, Elio, Rinaldi, Sabina, Rothwell, Joseph A, Scalbert, Augustin, Schmidt, Julie A, Severi, Gianluca, Sieri, Sabina, Vermeulen, Roel, Vincent, Emma E, Waldenberger, Melanie, Timpson, Nicholas J, and Johansson, Mattias

Subjects
2. Zero hunger, Male, Victoria, Incidence, Mendelian Randomization Analysis, Middle Aged, Risk Assessment, Kidney Neoplasms, 3. Good health, Body Mass Index, Europe, Risk Factors, Case-Control Studies, Metabolome, Humans, Metabolomics, Female, Obesity, Prospective Studies, Biomarkers, Aged
Abstract

BACKGROUND: Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI). METHODS AND FINDINGS: We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case-control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10-8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10-5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some-but not all-metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., -0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10-5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10-3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds. CONCLUSIONS: This study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI-the principal modifiable risk factor of kidney cancer.

Catalog

Books, media, physical & digital resources
See catalog results