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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 RL,  Gaudet MM,  Spurdle AB,  Fasching PA,  Couch FJ,  Benítez J,  Arias Pérez JI,  Zamora MP,  Malats N,  Dos Santos Silva I,  Gibson LJ,  Fletcher O,  Johnson N,  Anton-Culver H,  Ziogas A,  Figueroa J,  Brinton L,  Sherman ME,  Lissowska J,  Hopper JL,  Dite GS,  Apicella C,  Southey MC,  Sigurdson AJ,  Linet MS,  Schonfeld SJ,  Freedman DM,  Mannermaa A,  Kosma VM,  Kataja V,  Auvinen P,  Andrulis IL,  Glendon G,  Knight JA,  Weerasooriya N,  Cox A,  Reed MW,  Cross SS,  Dunning AM,  Ahmed S,  Shah M,  Brauch H,  Ko YD,  Brüning T,  GENICA Network,  Lambrechts D,  Reumers J,  Smeets A,  Wang-Gohrke S,  Hall P,  Czene K,  Liu J,  Irwanto AK,  Chenevix-Trench G,  Holland H,  kConFab,  AOCS,  Giles GG,  Baglietto L,  Severi G,  Bojensen SE,  Nordestgaard BG,  Flyger H,  John EM,  West DW,  Whittemore AS,  Vachon C,  Olson JE,  Fredericksen Z,  Kosel M,  Hein R,  Vrieling A,  Flesch-Janys D,  Heinz J,  Beckmann MW,  Heusinger K,  Ekici AB,  Haeberle L,  Humphreys MK,  Morrison J,  Easton DF,  Pharoah PD,  García-Closas M,  Goode EL,  Chang-Claude J
Journal: Breast Cancer Res
Date: 2010
Branches: MEB, REB
PubMed ID: 21194473
PMC ID: PMC3046455
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.