Title: Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors
Authors: Rudolph, Anja ×
Milne, Roger L
Truong, Thérèse
Knight, Julia A
Seibold, Petra
Flesch-Janys, Dieter
Behrens, Sabine
Eilber, Ursula
Bolla, Manjeet K
Wang, Qin
Dennis, Joe
Dunning, Alison M
Shah, Mitul
Munday, Hannah R
Darabi, Hatef
Eriksson, Mikael
Brand, Judith S
Olson, Janet
Vachon, Celine M
Hallberg, Emily
Castelao, J Esteban
Carracedo, Angel
Torres, Maria
Li, Jingmei
Humphreys, Keith
Cordina-Duverger, Emilie
Menegaux, Florence
Flyger, Henrik
Nordestgaard, Børge G
Nielsen, Sune F
Yesilyurt, Betul T
Floris, Beppe
Leunen, Karin
Engelhardt, Ellen G
Broeks, Annegien
Rutgers, Emiel J
Glendon, Gord
Mulligan, Anna Marie
Cross, Simon
Reed, Malcolm
Gonzalez-Neira, Anna
Arias Perez, José Ignacio
Provenzano, Elena
Apicella, Carmel
Southey, Melissa C
Spurdle, Amanda
kConFab Investigators
AOCS Group
Häberle, Lothar
Beckmann, Matthias W
Ekici, Arif B
Dieffenbach, Aida Karina
Arndt, Volker
Stegmaier, Christa
McLean, Catriona
Baglietto, Laura
Chanock, Stephen J
Lissowska, Jolanta
Sherman, Mark E
Brüning, Thomas
Hamann, Ute
Ko, Yon-Dschun
Orr, Nick
Schoemaker, Minouk
Ashworth, Alan
Kosma, Veli-Matti
Kataja, Vesa
Hartikainen, Jaana M
Mannermaa, Arto
Swerdlow, Anthony
Giles, Graham G
Brenner, Hermann
Fasching, Peter A
Chenevix-Trench, Georgia
Hopper, John
Benítez, Javier
Cox, Angela
Andrulis, Irene L
Lambrechts, Diether
Gago-Dominguez, Manuela
Couch, Fergus
Czene, Kamila
Bojesen, Stig E
Easton, Doug F
Schmidt, Marjanka K
Guénel, Pascal
Hall, Per
Pharoah, Paul D P
Garcia-Closas, Montserrat
Chang-Claude, Jenny #
Issue Date: Mar-2015
Publisher: Wiley-Liss
Series Title: International Journal of Cancer vol:136 issue:6 pages:E685-96
Article number: 10.1002/ijc.29188
Abstract: 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.
ISSN: 0020-7136
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gynaecological Oncology
Translational Cell & Tissue Research
Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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