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Open Access Research article

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

Sharon N Teraoka12*, Jonine L Bernstein3, Anne S Reiner3, Robert W Haile4, Leslie Bernstein5, Charles F Lynch6, Kathleen E Malone7, Marilyn Stovall8, Marinela Capanu3, Xiaolin Liang3, Susan A Smith8, Josyf Mychaleckyj19, Xuanlin Hou1, Lene Mellemkjaer10, John D Boice1112, Ashley Siniard13, David Duggan13, Duncan C Thomas4 and The WECARE Study Collaborative Group, and Patrick Concannon12

Author Affiliations

1 Center for Public Health Genomics, University of Virginia, P.O. Box 800717, Charlottesville, VA, 22908-0717, USA

2 Department of Biochemistry and Molecular Genetics, University of Virginia, P.O. Box 800733, Charlottesville, VA, USA

3 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 307 East 63rd Street, 3rd Floor, New York, NY, 10065, USA

4 Department of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90033, USA

5 Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA

6 Department of Epidemiology, University of Iowa, E220 General Hospital, Iowa City, IA, 52242, USA

7 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA, 98109, USA

8 Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd. unit 544, Houston, TX, 77030, USA

9 Department of Public Health Sciences, P.O. Box 800717, University of Virginia, Charlottesville, VA, 22908-0717, USA

10 Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark

11 International Epidemiology Institute, 1455 Research Boulevard, Suite 550, Rockville, MD, 20850-6115, USA

12 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 691 Preston Building, Nashville, TN, 37232-6838, USA

13 Translational Genomic Research Institute (TGen), 445 N. Fifth Street, Phoenix, AZ, 85004, USA

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Breast Cancer Research 2011, 13:R114  doi:10.1186/bcr3057

Published: 17 November 2011

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusions

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.