
Activities by Research Fields
Genetic Epidemiology in EPIC
The role of inherited genetic variation, particularly of common variants, in the etiology of noncommunicable diseases, particularly cancer, cardiovascular disease, and diabetes, is a major research theme within EPIC. Taking advantage of rapid technical innovations over the past decade, EPIC researchers have both led and collaborated in a wide range of candidate gene studies, genome-wide association studies (GWAS), and post-GWAS investigations, including investigations of gene—environment, gene—gene and gene—diet interactions and risk modelling. These studies are contributing to the understanding of genetic susceptibility to major noncommunicable diseases, with EPIC data contributing to the:
- Identification of a large number of susceptibility loci for most common cancers;
- Development of models for risk prediction and stratification with potential application in clinical and research settings;
- Elucidation of mechanisms of disease and biological pathways, providing potential targets for further research on strategies for prevention and treatment.
Over the past decade, genetic research in EPIC has benefited from the involvement and expertise of researchers and facilities in a number of centres of excellence across the EPIC centres and core institutes, such as: IARC, France; the German Cancer Research Center (DKFZ) in Heidelberg, Germany; and Imperial College London and the University of Cambridge, United Kingdom; as well as from collaboration with other leading international institutes, including the United States National Cancer Institute (NCI), Harvard University, and the University of Southern California. In addition to current studies on the genetic epidemiology of cancer, cardiovascular disease, and diabetes within EPIC, other notable projects include large international collaborative projects. For example, senior EPIC researchers were among the founding members of the NCI-funded Breast and Prostate Cancer Cohort Consortium (BPC3), which not only has made a significant contribution to our understanding of the genetic susceptibility to the most commonly diagnosed cancers among men and women but also has provided a model on which other large genetic cohort consortia have been based, such as the NCI-funded Pancreatic Cancer Cohort Consortium (PanScan), the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Ovarian Cancer Cohort Consortium (OC3).
EPIC is making a major contribution to the Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative, contributing approximately 23 000 samples from EPIC nested case—control studies of five cancer sites (breast, colorectum, lung, ovary, and prostate) to the OncoArray genotyping project. Specifically, the GAME-ON initiative aims to provide a rigorous knowledge base that will enable clinical translation and public health dissemination of the GWAS findings. The specific aims involving post-GWAS work within this project include: replication of previous findings and identification of new susceptibility loci through pooled or meta-analyses and extension of GWAS to diverse populations; fine-mapping of identified loci to better pinpoint causal variants; unravelling the function of identified genetic variants through functional and animal model studies; examining the effect of gene—gene and gene—environment interplay in modulating the risk of disease; and using the knowledge acquired from these studies to develop risk prediction mechanisms that can be used by the general population and in clinics.
Other key projects, major activities, and collaborations in EPIC by disease type include, for example:
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Breast Cancer
- Breast and Prostate Cancer Cohort Consortium (BPC3) – breast cancer hub – EPIC-led projects, including candidate gene studies, estrogen-receptor-negative breast cancer GWAS, gene—environment, gene—hormone, and risk modelling studies
- Breast Cancer Association Consortium (BCAC)
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Colorectal Cancer
- Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO)
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Ovarian Cancer
- Ovarian Cancer Cohort Consortium (OC3)
- Ovarian Cancer Association Consortium (OCAC)
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Pancreatic Cancer
- Pancreatic Cancer Cohort Consortium (PanScan)
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Prostate Cancer
- Breast and Prostate Cancer Cohort Consortium (BPC3) – activities including candidate gene studies, aggressive prostate cancer GWAS, gene—diet and gene—hormone studies
- PRACTICAL and Clinical Ellipse Consortia – post-GWAS studies
Selected publications
- Agudo A, Bonet C, Sala N et al. Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Carcinogenesis. 2013 Jun;34(6):1244-50. PMID: 23389292
- Amundadottir L, Kraft P, Stolzenberg-Solomon RZ et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet 2009 Sep;41(9):986-90. PMID: 19648918
- Beckmann L, Hüsing A, Setiawan VW et al. Comprehensive analysis of hormone and genetic variation in 36 genes related to steroid hormone metabolism in pre- and postmenopausal women from the Breast and Prostate Cancer Cohort Consortium (BPC3). J Clin Endocrinol Metab 2011 Feb;96(2):E360-7. PMID: 21177793
- Campa D, Kaaks R, Le Marchand L et al. Interactions between genetic variants and breast cancer risk factors in the Breast and Prostate Cancer Cohort Consortium. J Nat Cancer Inst 2011 Aug 17;103(16):1252-63. PMID: 21791674
- Canzian F, Cox DG, Setiawan VW et al. Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI Breast and Prostate Cancer Cohort Consortium. Hum Mol Genet 2010 Oct 1;19(19):3873-84. PMID: 20634197
- Cox DG, Blanché H, Pearce CL et al. A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). Breast Cancer Res. 2006;8(5):R54. PMID: 16987421
- Dossus L, Kaaks R, Canzian F et al. PTGS2 and IL6 genetic variation and risk of breast and prostate cancer: results from the Breast and Prostate Cancer Cohort Consortium (BPC3). Carcinogenesis 2010 Mar;31(3):455-61. PMID: 19965896
- Duell EJ, Sala N, Travier N et al. Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and aldehyde dehydrogenase (ALDH2), alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Carcinogenesis 2012 Feb;33(2):361-7. PMID: 22144473
- Hüsing A, Canzian F, Beckmann L et al. Prediction of breast cancer risk by genetic risk factors, overall and by hormone receptor status. J Med Genet 2012 Sep;49(9):601-8. PMID: 22972951
- Klein AP, Lindström S, Mendelsohn JB et al. An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population. PloS One 2013 Sep 13;8(9):e72311. PMID: 24058443
- Leenders M, Bhattacharjee S, Vineis P et al. Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4. Cancer Causes Control. 2013 Mar;24(3):595-602. PMID: 23334854
- Li D, Duell EJ, Yu K et al. Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer. Carcinogenesis 2012 Jul;33(7):1384-90. PMID: 22523087
- Petersen GM, Amundadottir L, Fuchs CS et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet. 2010 Mar;42(3):224-8. PMID: 20101243
- Sala N, Muñoz X, Travier N et al. Prostate stem-cell antigen gene is associated with diffuse and intestinal gastric cancer in Caucasians: results from the EPIC-EURGAST study. Int J Cancer. 2012 May 15;130(10):2417-27. PMID: 21681742
- Siddiq A, Couch FJ, Chen GK et al. A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11. Hum Mol Genet. 2012 Dec 15;21(24):5373-84. PMID: 22976474
- Tang H, Wei P, Duell EJ et al. Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene and pathway-based interaction analysis of GWAS data. Carcinogenesis 2014 Feb 10. PMID: 24419231
- Tang H, Wei P, Duell EJ et al. Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis. Cancer Epidemiol Biomarkers Prev. 2014 Jan;23(1):98-106. PMID: 24136929
- Tsilidis KK, Travis RC, Appleby PN et al. Insulin-like growth factor pathway genes and blood concentrations, dietary protein and risk of prostate cancer in the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). Int J Cancer. 2013 Jul 15;133(2):495-504. PMID: 23341348
- Wu C, Kraft P, Stolzenberg-Solomon R et al. Genome-wide association study of survival in patients with pancreatic adenocarcinoma. Gut. 2014 Jan;63(1):152-60. PMID: 23180869