Post-GWAS gene–environment interplay in breast cancer: results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79 000 women
Year: 2014
Type: review
Abstract: We studied the interplay between 39 breast cancer (BC) risk SNPs and established BC risk (body mass index, height, age at menarche, parity, age at menopause, smoking, alcohol and family history of BC) and prognostic factors (TNM stage, tumor grade, tumor size, age at diagnosis, estrogen receptor status and progesterone receptor status) as joint determinants of BC risk.We used a nested case -control design within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), with 16 285 BC cases and 19 376 controls.We performed stratified analyses for both the risk and prognostic factors, testing for heterogeneity for the risk factors, and case -case comparisons for differential associations of polymorphisms by subgroups of the prognostic factors.We analyzed multiplicative interactions between the SNPs and the risk factors.Finally, we also performed a meta-analysis of the interaction ORs from BPC3 and the Breast Cancer Association Consortium.After correction for multiple testing, no significant interaction between the SNPs and the established risk factors in the BPC3 study was found.The meta-analysis showed a suggestive interaction between smoking status and SLC4A7-rs4973768 (P interaction 5 8.84 3 10 24 ) which, although not significant after considering multiple comparison, has a plausible biological explanation.In conclusion, in this study of up to almost 79 000 women we can conclusively exclude any novel major interactions between genome-wide association studies hits and the epidemiologic risk factors taken into consideration, but we propose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC. a Genome Reference Consortium Human, build 37 (http://genome.ucsc.edu/cgi-bin/hgGateway). b This SNP was included in the first analyses conducted in this dataset.c 5p12-rs4415084 or surrogate 5p12-rs920329.d 6q14-rs1917063 or surrogate 6q14-rs9344208.e 6q14-rs9344191 or surrogate 6q14-rs9449341.f ECHDC1, RNF146-rs2180341 or surrogate ECHDC1, RNF146-rs9398840.g ZMIZ1-rs1250003 or surrogate ZMIZ1-rs704010.h RAD51L1-rs999737 or surrogate RAD51L1-rs10483813.i RALY-rs2284378 or surrogate RALY-rs6059651, RALY-rs8119937.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddu223
Authors: Myrto Barrdahl, Federico Canzian, Amit D. Joshi, Ruth C. Travis, Jenny Chang-Claude, Paul L. Auer, Susan M. Gapstur, Mia Gaudet, W. Ryan Diver, Brian E. Henderson, Christopher A. Haiman, Fredrick R. Schumacher, Loïc Le Marchand, Christine D. Berg, Stephen J. Chanock, Robert N. Hoover, Anja Rudolph, Regina G. Ziegler, Graham G. Giles, Laura Baglietto, Gianluca Severi, Susan E. Hankinson, Sara Lindström, Walter Willet, David J. Hunter, Julie E. Buring, I-Min Lee, Shumin Zhang, Laure Dossus, David G. Cox, Kay-Tee Khaw, Eiliv Lund, Alessio Naccarati, Petra H. Peeters, J. Ramón Quirós, Elio Riboli, Malin Sund, Dimitrios Trichopoulos, Ross L. Prentice, Peter Kraft, Rudolf Kaaks, Daniele Campa
Institutions: German Cancer Research Center, Harvard University, University of Oxford, Fred Hutch Cancer Center, University of Wisconsin–Milwaukee, American Cancer Society, University of Southern California, University of Hawaiʻi at Mānoa, University of Hawaii System, University of Hawaii Cancer Center, National Cancer Institute, Division of Cancer Epidemiology and Genetics, The University of Melbourne, Cancer Council Victoria, Monash University, Brigham and Women's Hospital, University of Massachusetts Amherst, Université Paris-Sud, Inserm, Institut Gustave Roussy, Centre de recherche en Epidémiologie et Santé des Populations, Lyon 1 Université, Centre National de la Recherche Scientifique, Université de Lyon, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Imperial College London, University of Cambridge, UiT The Arctic University of Norway, Italian institute for Genomic Medicine, University Medical Center Utrecht, Umeå University, Academy of Athens, Hellenic Health Foundation
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: G1148307873, G1165142596, G1420790711, Discovery, Biology and Risk of Inherited Variants in Breast Cancer, G2919159421, G3255761503, Characterizing Genetic Susceptibility to Breast and Prostate Cancer: The BPC3., G3796112702, G395156118, G4021838900, G4103474500, G433713863, G4430667546, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G4940192625, G5021959070, G5547620395, G5624510383, G5897142711, G614814196, NIHR Senior Investigator Award, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G6723261869, G6967911674, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G8013581208, G8536616440, University of Hawaii Cancer Center CCSG
OpenAlex ID: W2161116593