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Breast Cancer Research
Published in: Breast Cancer Research 6/2010

Open Access 01-12-2010 | Research article

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: Roger L Milne, Mia M Gaudet, Amanda B Spurdle, Peter A Fasching, Fergus J Couch, Javier Benítez, José Ignacio Arias Pérez, M Pilar Zamora, Núria Malats, Isabel dos Santos Silva, Lorna J Gibson, Olivia Fletcher, Nichola Johnson, Hoda Anton-Culver, Argyrios Ziogas, Jonine Figueroa, Louise Brinton, Mark E Sherman, Jolanta Lissowska, John L Hopper, Gillian S Dite, Carmel Apicella, Melissa C Southey, Alice J Sigurdson, Martha S Linet, Sara J Schonfeld, D Michal Freedman, Arto Mannermaa, Veli-Matti Kosma, Vesa Kataja, Päivi Auvinen, Irene L Andrulis, Gord Glendon, Julia A Knight, Nayana Weerasooriya, Angela Cox, Malcolm WR Reed, Simon S Cross, Alison M Dunning, Shahana Ahmed, Mitul Shah, Hiltrud Brauch, Yon-Dschun Ko, Thomas Brüning, Diether Lambrechts, Joke Reumers, Ann Smeets, Shan Wang-Gohrke, Per Hall, Kamila Czene, Jianjun Liu, Astrid K Irwanto, Georgia Chenevix-Trench, Helene Holland, Graham G Giles, Laura Baglietto, Gianluca Severi, Stig E Bojensen, Børge G Nordestgaard, Henrik Flyger, Esther M John, Dee W West, Alice S Whittemore, Celine Vachon, Janet E Olson, Zachary Fredericksen, Matthew Kosel, Rebecca Hein, Alina Vrieling, Dieter Flesch-Janys, Judith Heinz, Matthias W Beckmann, Katharina Heusinger, Arif B Ekici, Lothar Haeberle, Manjeet K Humphreys, Jonathan Morrison, Doug F Easton, Paul D Pharoah, Montserrat García-Closas, Ellen L Goode, Jenny Chang-Claude, GENICA Network, kConFab, AOCS

Published in: Breast Cancer Research | Issue 6/2010

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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.
Appendix
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Metadata
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
Roger L Milne
Mia M Gaudet
Amanda B Spurdle
Peter A Fasching
Fergus J Couch
Javier Benítez
José Ignacio Arias Pérez
M Pilar Zamora
Núria Malats
Isabel dos Santos Silva
Lorna J Gibson
Olivia Fletcher
Nichola Johnson
Hoda Anton-Culver
Argyrios Ziogas
Jonine Figueroa
Louise Brinton
Mark E Sherman
Jolanta Lissowska
John L Hopper
Gillian S Dite
Carmel Apicella
Melissa C Southey
Alice J Sigurdson
Martha S Linet
Sara J Schonfeld
D Michal Freedman
Arto Mannermaa
Veli-Matti Kosma
Vesa Kataja
Päivi Auvinen
Irene L Andrulis
Gord Glendon
Julia A Knight
Nayana Weerasooriya
Angela Cox
Malcolm WR Reed
Simon S Cross
Alison M Dunning
Shahana Ahmed
Mitul Shah
Hiltrud Brauch
Yon-Dschun Ko
Thomas Brüning
Diether Lambrechts
Joke Reumers
Ann Smeets
Shan Wang-Gohrke
Per Hall
Kamila Czene
Jianjun Liu
Astrid K Irwanto
Georgia Chenevix-Trench
Helene Holland
Graham G Giles
Laura Baglietto
Gianluca Severi
Stig E Bojensen
Børge G Nordestgaard
Henrik Flyger
Esther M John
Dee W West
Alice S Whittemore
Celine Vachon
Janet E Olson
Zachary Fredericksen
Matthew Kosel
Rebecca Hein
Alina Vrieling
Dieter Flesch-Janys
Judith Heinz
Matthias W Beckmann
Katharina Heusinger
Arif B Ekici
Lothar Haeberle
Manjeet K Humphreys
Jonathan Morrison
Doug F Easton
Paul D Pharoah
Montserrat García-Closas
Ellen L Goode
Jenny Chang-Claude
GENICA Network
kConFab
AOCS
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2010
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2797

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