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Single-nucleotide polymorphisms in DNA bypass polymerase genes and association with breast cancer and breast cancer subtypes among African Americans and Whites

  • Epidemiology
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Abstract

DNA damage recognition and repair is a complex system of genes focused on maintaining genomic stability. Recently, there has been a focus on how breast cancer susceptibility relates to genetic variation in the DNA bypass polymerases pathway. Race-stratified and subtype-specific logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between 22 single-nucleotide polymorphisms (SNPs) in seven bypass polymerase genes and breast cancer risk in the Carolina Breast Cancer Study, a population-based, case–control study (1,972 cases and 1,776 controls). We used SNP-set kernel association test (SKAT) to evaluate the multi-gene, multi-locus (combined) SNP effects within bypass polymerase genes. We found similar ORs for breast cancer with three POLQ SNPs (rs487848 AG/AA vs. GG; OR = 1.31, 95 % CI 1.03–1.68 for Whites and OR = 1.22, 95 % CI 1.00–1.49 for African Americans), (rs532411 CT/TT vs. CC; OR = 1.31, 95 % CI 1.02–1.66 for Whites and OR = 1.22, 95 % CI 1.00–1.48 for African Americans), and (rs3218634 CG/CC vs. GG; OR = 1.29, 95 % CI 1.02–1.65 for Whites). These three SNPs are in high linkage disequilibrium in both races. Tumor subtype analysis showed the same SNPs to be associated with increased risk of Luminal breast cancer. SKAT analysis showed no significant combined SNP effects. These results suggest that variants in the POLQ gene may be associated with the risk of Luminal breast cancer.

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Acknowledgments

The authors would like to thank the participants of the Carolina Breast Cancer Study, the UNC BioSpecimen Processing Facility for our DNA extractions, blood processing, storage, and sample disbursement (https://genome.unc.edu/bsp), the UNC Mammalian Genotyping Core for CBCS sample genotyping (http://mgc.unc.edu), and Jessica Tse and Katie O’Brien for their technical assistance and support. Finally, we would like to acknowledge Dr. Robert Millikan, the previous Principal Investigator of the CBCS, for his guidance and inspiration for this paper. This research was funded in part by the University Cancer Research Fund of North Carolina, the National Cancer Institute Specialized Program of Research Excellence (SPORE) in Breast Cancer (NIH/NCI P50-CA58223).

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Authors and Affiliations

  1. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA

    Leila Family, Jeannette T. Bensen, Melissa A. Troester & Andrew F. Olshan

  2. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    Jeannette T. Bensen, Melissa A. Troester, Carey K. Anders & Andrew F. Olshan

  3. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA

    Michael C. Wu

  4. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Michael C. Wu

  5. Division of Hematology-Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA

    Carey K. Anders

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  1. Leila Family
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Correspondence to Leila Family.

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Family, L., Bensen, J.T., Troester, M.A. et al. Single-nucleotide polymorphisms in DNA bypass polymerase genes and association with breast cancer and breast cancer subtypes among African Americans and Whites. Breast Cancer Res Treat 149, 181–190 (2015). https://doi.org/10.1007/s10549-014-3203-4

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