TY - JOUR
T1 - Post-GWAS gene-environment interplay in breast cancer
T2 - Results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79 000 women
AU - Barrdahl, Myrto
AU - Canzian, Federico
AU - Joshi, Amit D.
AU - Travis, Ruth C.
AU - Chang-Claude, Jenny
AU - Auer, Paul L.
AU - Gapstur, Susan M.
AU - Gaudet, Mia
AU - Diver, W. Ryan
AU - Henderson, Brian E.
AU - Haiman, Christopher A.
AU - Schumacher, Fredrick R.
AU - Le Marchand, Loïc
AU - Berg, Christine D.
AU - Chanock, Stephen J.
AU - Hoover, Robert N.
AU - Rudolph, Anja
AU - Ziegler, Regina G.
AU - Giles, Graham G.
AU - Baglietto, Laura
AU - Severi, Gianluca
AU - Hankinson, Susan E.
AU - Lindström, Sara
AU - Willet, Walter
AU - Hunter, David J.
AU - Buring, Julie E.
AU - Lee, I. Min
AU - Zhang, Shumin
AU - Dossus, Laure
AU - Cox, David G.
AU - Khaw, Kay Tee
AU - Lund, Eiliv
AU - Naccarati, Alessio
AU - Peeters, Petra H.
AU - Quirós, J. Ramón
AU - Riboli, Elio
AU - Sund, Malin
AU - Trichopoulos, Dimitrios
AU - Prentice, Ross L.
AU - Kraft, Peter
AU - Kaaks, Rudolf
AU - Campa, Daniele
N1 - Publisher Copyright:
© 2014. Published by Oxford University Press.
PY - 2014/11/2
Y1 - 2014/11/2
N2 - 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 (TNMstage, tumor grade, tumor size, age at diagnosis, estrogenreceptor statusandprogesterone 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 (Pinteraction =8.84 3 10-4) 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 hitsandthe epidemiologic risk factors takeninto consideration, butwepropose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC.
AB - 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 (TNMstage, tumor grade, tumor size, age at diagnosis, estrogenreceptor statusandprogesterone 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 (Pinteraction =8.84 3 10-4) 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 hitsandthe epidemiologic risk factors takeninto consideration, butwepropose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC.
UR - http://www.scopus.com/inward/record.url?scp=84929481929&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddu223
DO - 10.1093/hmg/ddu223
M3 - Article
C2 - 24895409
AN - SCOPUS:84929481929
SN - 0964-6906
VL - 23
SP - 5260
EP - 5270
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 19
ER -