Single nucleotide polymorphisms associated with risk for contralateral breast cancer in the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study

Sharon N Teraoka; Jonine L Bernstein; Anne S Reiner; Robert W Haile; Leslie Bernstein; Charles F Lynch; Kathleen E Malone; Marilyn Stovall; Marinela Capanu; Xiaolin Liang; Susan A Smith; Josyf Mychaleckyj; Xuanlin Hou; Lene Mellemkjaer; John D Boice Jr; Ashley Siniard; David Duggan; Duncan C Thomas; Patrick Concannon; WECARE Study Collaborative Group

doi:10.1186/bcr3057

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Single nucleotide polymorphisms associated with risk for contralateral breast cancer in the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study

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Single nucleotide polymorphisms associated with risk for contralateral breast cancer in the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study

Sharon N Teraoka, Jonine L Bernstein, Anne S Reiner, Robert W Haile, Leslie Bernstein, Charles F Lynch, Kathleen E Malone, Marilyn Stovall, Marinela Capanu, Xiaolin Liang, …

Breast cancer research : BCR, Vol.13(6), pp.R114-R114

2011

DOI: 10.1186/bcr3057

PMCID: PMC3326556

PMID: 22087758

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Abstract

Genome-wide association studies, focusing primarily on unilateral breast cancer, have identified single nucleotide polymorphisms (SNPs) in a number of genomic regions that have alleles associated with a significantly increased risk of breast cancer. In the current study we evaluate the contributions of these previously identified regions to the risk of developing contralateral breast cancer. The most strongly disease-associated SNPs from prior studies were tested for association with contralateral breast cancer. A subset of these SNPs, selected upon their main effects on contralateral breast cancer risk was further evaluated for interaction with treatment modalities and estrogen receptor (ER) status. We genotyped 21 SNPs in 708 women with contralateral breast cancer and 1394 women with unilateral breast cancer who serve as the cases and controls in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study. Records of treatment and ER status were available for most of WECARE Study participants. Associations of SNP genotypes and risk for contralateral breast cancer were calculated with multivariable adjusted conditional logistic regression methods. Multiple SNPs in the FGFR2 locus were significantly associated with contralateral breast cancer, including rs1219648 (per allele rate ratio (RR) = 1.25, 95%CI = 1.08-1.45). Statistically significant associations with contralateral breast cancer were also observed at rs7313833, near the PTHLH gene (per allele RR = 1.26, 95%CI = 1.08-1.47), rs13387042 (2q35) (per allele RR = 1.19, 95%CI = 1.02-1.37), rs13281615 (8q24) (per allele RR = 1.21, 95%CI = 1.04-1.40), and rs11235127 near TMEM135 (per allele RR = 1.26, 95%CI = 1.04-1.53). The A allele of rs13387042 (2q35) was significantly associated with contralateral breast cancer in ER negative first tumors while the A allele of rs11235127 (near TMEM135) was significantly associated with contralateral breast cancer in ER positive first tumors. Although some SNP genotypes appeared to modify contralateral breast cancer risk with respect to tamoxifen treatment or particular radiation doses, trend tests for such effects were not significant. Our results indicate that some common risk variants associated with primary breast cancer also increase risk for contralateral breast cancer, and that these risks vary with the ER status of the first tumor.

Genetic Predisposition to Disease

Genome-Wide Association Study

Receptors, Estrogen - genetics

Humans

Genotype

Risk

Case-Control Studies

Breast Neoplasms - radiotherapy

Breast Neoplasms - genetics

Alleles

Female

Polymorphism, Single Nucleotide

Receptor, Fibroblast Growth Factor, Type 2 - genetics

Breast Neoplasms - epidemiology

Details

Title: Subtitle: Single nucleotide polymorphisms associated with risk for contralateral breast cancer in the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study
Creators: Sharon N Teraoka - Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908-0717, USA. st3x@virginia.edu
Jonine L Bernstein
Anne S Reiner
Robert W Haile
Leslie Bernstein
Charles F Lynch
Kathleen E Malone
Marilyn Stovall
Marinela Capanu
Xiaolin Liang
Susan A Smith
Josyf Mychaleckyj
Xuanlin Hou - University of Virginia
Lene Mellemkjaer
John D Boice Jr
Ashley Siniard
David Duggan
Duncan C Thomas
Patrick Concannon
WECARE Study Collaborative Group
Resource Type: Journal article
Publication Details: Breast cancer research : BCR, Vol.13(6), pp.R114-R114
DOI: 10.1186/bcr3057
PMID: 22087758
PMCID: PMC3326556
NLM abbreviation: Breast Cancer Res
ISSN: 1465-5411
eISSN: 1465-542X
Publisher: England
Grant note: R01 CA129639 / NCI NIH HHS R01 CA057569 / NCI NIH HHS U01 CA083178 / NCI NIH HHS R01 AG014358 / NIA NIH HHS R01 CA112450 / NCI NIH HHS R01 CA097397 / NCI NIH HHS R01 CA57569 / NCI NIH HHS R01 CA114236 / NCI NIH HHS
Language: English
Date published: 2011
Academic Unit: Epidemiology
Record Identifier: 9983995111102771

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