TY - JOUR

T1 - Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

AU - Rudolph, Anja

AU - Milne, Roger L

AU - Truong, Thérèse

AU - Knight, Julia A

AU - Seibold, Petra

AU - Flesch-Janys, Dieter

AU - Behrens, Sabine

AU - Eilber, Ursula

AU - Bolla, Manjeet K

AU - Wang, Qin

AU - Dennis, Joe

AU - Dunning, Alison M

AU - Shah, Mitul

AU - Munday, Hannah R

AU - Darabi, Hatef

AU - Eriksson, Mikael

AU - Brand, Judith S

AU - Olson, Janet

AU - Vachon, Celine M

AU - Hallberg, Emily

AU - Castelao, J Esteban

AU - Carracedo, Angel

AU - Torres, Maria

AU - Li, Jingmei

AU - Humphreys, Keith

AU - Cordina-Duverger, Emilie

AU - Menegaux, Florence

AU - Flyger, Henrik

AU - Nordestgaard, Børge G

AU - Nielsen, Sune F

AU - Yesilyurt, Betul T

AU - Floris, Giuseppe

AU - Leunen, Karin

AU - Engelhardt, Ellen G

AU - Broeks, Annegien

AU - Rutgers, Emiel J

AU - Glendon, Gord

AU - Mulligan, Anna Marie

AU - Cross, Simon

AU - Reed, Malcolm

AU - Gonzalez-Neira, Anna

AU - Arias Perez, José Ignacio

AU - Provenzano, Elena

AU - Apicella, Carmel

AU - Southey, Melissa C

AU - Spurdle, Amanda

AU - Häberle, Lothar

AU - Beckmann, Matthias W

AU - Ekici, Arif B

AU - Bojesen, Stig E

AU - kConFab Investigators

N1 - © 2014 UICC.

PY - 2015/3

Y1 - 2015/3

N2 - A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint ) <1.1 × 10(-3) . None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women ≥170 cm (OR = 1.22, p = 0.017), but inversely associated with ER-negative BC risk in women <160 cm (OR = 0.83, p = 0.039, pint = 1.9 × 10(-4) ). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR = 0.85, p = 2.0 × 10(-4) ), and absent in women who had had just one (OR = 0.96, p = 0.19, pint = 6.1 × 10(-4) ). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR = 0.93, p = 2.8 × 10(-5) ), but no association was observed in current smokers (OR = 1.07, p = 0.14, pint = 3.4 × 10(-4) ). In conclusion, recently identified BC susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies.

AB - A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint ) <1.1 × 10(-3) . None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women ≥170 cm (OR = 1.22, p = 0.017), but inversely associated with ER-negative BC risk in women <160 cm (OR = 0.83, p = 0.039, pint = 1.9 × 10(-4) ). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR = 0.85, p = 2.0 × 10(-4) ), and absent in women who had had just one (OR = 0.96, p = 0.19, pint = 6.1 × 10(-4) ). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR = 0.93, p = 2.8 × 10(-5) ), but no association was observed in current smokers (OR = 1.07, p = 0.14, pint = 3.4 × 10(-4) ). In conclusion, recently identified BC susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies.

KW - Breast Neoplasms

KW - Female

KW - Gene-Environment Interaction

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Humans

KW - Polymorphism, Single Nucleotide

KW - Receptors, Estrogen

KW - Risk Factors

U2 - 10.1002/ijc.29188

DO - 10.1002/ijc.29188

M3 - Journal article

C2 - 25227710

VL - 136

SP - E685-E696

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 6

ER -