Title: Evidence of Gene-Environment Interactions between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors
Authors: Nickels, Stefan ×
Truong, Thérèse
Hein, Rebecca
Stevens, Kristen
Buck, Katharina
Behrens, Sabine
Eilber, Ursula
Schmidt, Martina
Häberle, Lothar
Vrieling, Alina
Gaudet, Mia
Figueroa, Jonine
Schoof, Nils
Spurdle, Amanda B
Rudolph, Anja
Fasching, Peter A
Hopper, John L
Makalic, Enes
Schmidt, Daniel F
Southey, Melissa C
Beckmann, Matthias W
Ekici, Arif B
Fletcher, Olivia
Gibson, Lorna
Dos Santos Silva, Isabel
Peto, Julian
Humphreys, Manjeet K
Wang, Jean
Cordina-Duverger, Emilie
Menegaux, Florence
Nordestgaard, Børge G
Bojesen, Stig E
Lanng, Charlotte
Anton-Culver, Hoda
Ziogas, Argyrios
Bernstein, Leslie
Clarke, Christina A
Brenner, Hermann
Müller, Heiko
Arndt, Volker
Stegmaier, Christa
Brauch, Hiltrud
Brüning, Thomas
Harth, Volker
The Genica Network
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M
Group, Aocs Management
Lambrechts, Diether
Smeets, Dominiek
Neven, Patrick
Paridaens, Robert
Flesch-Janys, Dieter
Obi, Nadia
Wang-Gohrke, Shan
Couch, Fergus J
Olson, Janet E
Vachon, Celine M
Giles, Graham G
Severi, Gianluca
Baglietto, Laura
Offit, Kenneth
John, Esther M
Miron, Alexander
Andrulis, Irene L
Knight, Julia A
Glendon, Gord
Mulligan, Anna Marie
Chanock, Stephen J
Lissowska, Jolanta
Liu, Jianjun
Cox, Angela
Cramp, Helen
Connley, Dan
Balasubramanian, Sabapathy
Dunning, Alison M
Shah, Mitul
Trentham-Dietz, Amy
Newcomb, Polly
Titus, Linda
Egan, Kathleen
Cahoon, Elizabeth K
Rajaraman, Preetha
Sigurdson, Alice J
Doody, Michele M
Guénel, Pascal
Pharoah, Paul D P
Schmidt, Marjanka K
Hall, Per
Easton, Doug F
Garcia-Closas, Montserrat
Milne, Roger L
Chang-Claude, Jenny #
Issue Date: Mar-2013
Publisher: Public Library of Science
Series Title: PLoS Genetics vol:9 issue:3 pages:e1003284
Article number: 10.1371/journal.pgen.1003284
Abstract: Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4×10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1×10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85) in those who drank ≥20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3×10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.
ISSN: 1553-7390
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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