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Genetic variants on chromosome 5p12 are associated with risk of breast cancer in African American women: the Black Women’s Health Study

  • Epidemiology
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Abstract

Two single nucleotide polymorphisms (SNPs), rs4415084, and rs10941679 on chromosome 5p12 were associated with risk of breast cancer in a recent genome-wide association study (GWAS) of women of European ancestry. Both SNPs are located in a large high-LD region and the causal variant(s) are still unknown. We conducted a nested case–control study in a cohort of African American women to replicate and narrow the region carrying the causal variant(s). We evaluated 14 tagging SNPs in a 98 kb LD block surrounding the index SNPs in 886 breast cancer cases and 1,089 controls from the Black Women’s Health Study. We used the Cochran–Armitage trend test to assess association with breast cancer risk. Odds ratios were derived from logistic regression analyses adjusted for potential confounders including percent European admixture. We confirmed the reported association of rs4415084 SNP with overall risk of breast cancer (P = 0.06), and, as in the original study, observed a stronger association with estrogen receptor positive tumors (P = 0.03). We identified four other SNPs (rs6451770, rs12515012, rs13156930, and rs16901937) associated with risk of breast cancer at the nominal alpha value of 0.05; all of them were located in a 59 kb HapMap YRI LD block. After correction for multiple testing, the association with SNP rs16901937 remained significant (P permutated = 0.038). The G allele was associated with a 21% increased risk of breast cancer overall and with a 32% increase in tumors positive for both estrogen and progesterone receptors. The present results from an African ancestry (AA) population confirm the presence of breast cancer susceptibility genetic variants in the chromosome 5p12 region. We successfully used the shorter range of LD in our AA sample to refine the localization of the putative causal variant.

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Acknowledgments

We thank the Black Women’s Health Study participants for their continuing participation in this research effort. This work was supported by grants R01CA058420 and R01CA098663 from the National Cancer Institute, Division of Cancer Control and Population Science (http://www.cancercontrol.cancer.gov). The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research Resources (http://www.broadinstitute.org/sections/science/projects/broad/ncrr-center-genotyping-analysis).

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Authors and Affiliations

  1. Slone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, Boston, MA, 02215, USA

    Edward A. Ruiz-Narvaez, Lynn Rosenberg, Deborah A. Boggs, Yvette C. Cozier & Julie R. Palmer

  2. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

    Edward A. Ruiz-Narvaez, Lynn Rosenberg, Yvette C. Cozier & Julie R. Palmer

  3. Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

    Charles N. Rotimi & Adebowale Adeyemo

  4. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

    L. Adrienne Cupples

  5. Georgetown University Medical Center, Washington, DC, USA

    Lucile L. Adams-Campbell

Authors
  1. Edward A. Ruiz-Narvaez
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  2. Lynn Rosenberg
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  3. Charles N. Rotimi
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  4. L. Adrienne Cupples
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  5. Deborah A. Boggs
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  6. Adebowale Adeyemo
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  7. Yvette C. Cozier
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  8. Lucile L. Adams-Campbell
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  9. Julie R. Palmer
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Correspondence to Julie R. Palmer.

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Ruiz-Narvaez, E.A., Rosenberg, L., Rotimi, C.N. et al. Genetic variants on chromosome 5p12 are associated with risk of breast cancer in African American women: the Black Women’s Health Study. Breast Cancer Res Treat 123, 525–530 (2010). https://doi.org/10.1007/s10549-010-0775-5

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  • DOI: https://doi.org/10.1007/s10549-010-0775-5

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