Title: Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the Breast Cancer Association Consortium: a combined case-control study
Authors: Milne, Roger L ×
Gaudet, Mia M
Spurdle, Amanda B
Fasching, Peter A
Couch, Fergus J
Benitez, Javier
Arias Perez, Jose Ignacio
Zamora, Maria Pilar
Malats, Nuria
Dos Santos Silva, Isabel
Gibson, Lorna J
Fletcher, Olivia
Johnson, Nichola
Anton-Culver, Hoda
Ziogas, Argyrios
Figueroa, Jonine
Brinton, Louise
Sherman, Mark E
Lissowska, Jolanta
Hopper, John L
Dite, Gillian S
Apicella, Carmel
Southey, Melissa C
Sigurdson, Alice J
Linet, Martha S
Schonfeld, Sara J
Freedman, D Michal
Mannermaa, Arto
Kosma, Veli-Matti
Kataja, Vesa
Auvinen, Paivi
Andrulis, Irene L
Glendon, Gord
Knight, Julia A
Weerasooriya, Nayana
Cox, Angela
Reed, Malcolm Wr
Cross, Simon S
Dunning, Alison M
Ahmed, Shahana
Shah, Mitul
Brauch, Hiltrud
Bruning, Thomas
Genica Network, The
Lambrechts, Diether
Reumers, Joke
Smeets, Ann
Wang-Gohrke, Shan
Hall, Per
Czene, Kamila
Liu, Jianjun
Irwanto, Astrid K
Chenevix-Trench, Georgia
Holland, Helene
Kconfab Investigators, The
Aocs Investigators, The
Giles, Graham G
Severi, Gianluca
Baglietto, Laura
Bojesen, Stig E
Nordestgaard, Borge G
Flyger, Henrik
John, Esther M
West, Dee W
Whittemore, Alice S
Vachon, Celine
Olson, Janet E
Fredericksen, Zachary
Kosel, Matthew
Hein, Rebecca
Vrieling, Alina
Flesch-Janys, Dieter
Heinz, Judith
Beckmann, Matthias
Heusinger, Katharina
Ekici, Arif B
Haeberle, Lothar
Easton, Douglas F
Humphreys, Manjeet K
Morrison, Jonathan
Pharoah, Paul D
Garcia-Closas, Montserrat
Goode, Ellen L
Chang-Claude, Jenny #
Issue Date: Dec-2010
Publisher: Biomed Central Ltd
Series Title: Breast Cancer Research vol:12 issue:6 pages:R110
Article number: R110
Abstract: ABSTRACT: INTRODUCTION: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. METHODS: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 [FGFR2], 8q24-rs13281615, 11p15-rs3817198 [LSP1], 5q11-rs889312 [MAP3K1], 16q12-rs3803662 [TOX3], 2q35-rs13387042, 5p12-rs10941679 [MRPS30], 17q23-rs6504950 [COX11], 3p24-rs4973768 [SLC4A7], CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. RESULTS: These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. CONCLUSIONS: The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified.
ISSN: 1465-542X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Multidisciplinary Breast Clinic Section (-)
Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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