Breast Cancer Research and Treatment

, Volume 106, Issue 2, pp 273–280 | Cite as

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

  • Jun Wang
  • Russell Higuchi
  • Francesmary Modugno
  • Jia Li
  • Nanette Umblas
  • Jocelyn Lee
  • Li-Yung Lui
  • Elad Ziv
  • Jeffery A. Tice
  • Steven R. Cummings
  • Brian Rhees


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.


Estrogen receptor alpha Haplotype Single nucleotide polymorphism Association Breast cancer 



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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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Jun Wang
    • 1
  • Russell Higuchi
    • 1
  • Francesmary Modugno
    • 2
    • 3
  • Jia Li
    • 1
  • Nanette Umblas
    • 1
  • Jocelyn Lee
    • 1
  • Li-Yung Lui
    • 4
    • 5
  • Elad Ziv
    • 6
  • Jeffery A. Tice
    • 5
    • 6
  • Steven R. Cummings
    • 4
    • 5
  • Brian Rhees
    • 7
  1. 1.Human Genetics DepartmentRoche Molecular Systems, Inc. AlamedaUSA
  2. 2.Department of Epidemiology, Graduate School of Public HealthUniversity of PittsburghPittsburghUSA
  3. 3.University of Pittsburgh Cancer Institute PittsburghUSA
  4. 4.California Pacific Medical Center Research InstituteSan FranciscoUSA
  5. 5.San Francisco Coordinating CenterSan FranciscoUSA
  6. 6.Department of MedicineUniversity of California (San Francisco)San FranciscoUSA
  7. 7.Department of Biostatistics and BioinformaticsRoche Molecular Systems, Inc.AlamedaUSA

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