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Estrogen receptor alpha haplotypes and breast cancer risk in older Caucasian women

  • Epidemiology
  • Published:
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Abstract

Life-long exposure to estrogen is an established risk factor for breast cancer development. The underlying mechanism has been suggested to be the binding of estrogen-to-estrogen receptors in mammary tissue, which in turn promotes the proliferation and differentiation of breast tissue. Polymorphisms and haplotypes in estrogen receptor alpha (ESR1) have been reportedly associated with breast cancer risk; however, the results are not fully consistent. In this study, we investigated breast cancer risk associated with genotypes and haplotypes resulting from four ESR1 single nucleotide polymorphisms (SNPs), rs746432, rs2234693, rs9340799, and rs1801132. Genotyping has been performed on 393 breast cancer cases and 790 randomly selected controls in 1,183 Caucasian women over age 65 from the Study of Osteoporotic Fractures (SOF). We observed an allelic protective effect for SNP rs9340799 with an estimated odds ratio (OR) of 0.82 (95% CI = 0.68–1.00; P = 0.04) after adjustment for age, BMI and hip BMD. A protective effect of this SNP has been reported before in several different studies. We did not replicate the previously reported C–C–A–G haplotype association to breast cancer—the C–C–A–G haplotype from these SNPs was rare in this study (estimated frequency below 0.001% in cases and controls). No other statistically significant associations were observed between ESR1 haplotypes from the same four SNPs and the risk of breast cancer in older Caucasian women.

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Acknowledgements

The Study of Osteoporotic Fractures is supported by National Institutes of Health funding, under the following Grant Numbers: AG05407, AR35582, AG05394, AR35584, and AR35583.

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Authors and Affiliations

  1. Human Genetics Department, Roche Molecular Systems, Inc., 1145 Atlantic Ave, Alameda, CA, 94555, USA

    Jun Wang, Russell Higuchi, Jia Li, Nanette Umblas & Jocelyn Lee

  2. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    Francesmary Modugno

  3. University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Francesmary Modugno

  4. California Pacific Medical Center Research Institute, San Francisco, CA, USA

    Li-Yung Lui & Steven R. Cummings

  5. San Francisco Coordinating Center, San Francisco, CA, USA

    Li-Yung Lui, Jeffery A. Tice & Steven R. Cummings

  6. Department of Medicine, University of California (San Francisco), San Francisco, CA, USA

    Elad Ziv & Jeffery A. Tice

  7. Department of Biostatistics and Bioinformatics, Roche Molecular Systems, Inc., Alameda, CA, USA

    Brian Rhees

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  1. Jun Wang
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  2. Russell Higuchi
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Correspondence to Jun Wang.

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Wang, J., Higuchi, R., Modugno, F. et al. Estrogen receptor alpha haplotypes and breast cancer risk in older Caucasian women. Breast Cancer Res Treat 106, 273–280 (2007). https://doi.org/10.1007/s10549-007-9497-8

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  • DOI: https://doi.org/10.1007/s10549-007-9497-8

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