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Synergistic Effects of Polymorphisms in DNA Repair Genes and Endogenous Estrogen Exposure on Female Breast Cancer Risk

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Endogenous estrogen is suggested to initiate cell proliferation and cause oxidative DNA damage during breast tumorigenesis. Cells eliminate DNA damage by means of repair enzymes. Genotypic variants of DNA damage repair genes, participating in base excision repair (BER) and nucleotide excision repair (NER) pathways, may act as modifiers that affect the association between estrogen exposure and breast cancer.

Methods

In a hospital-based case–control study of female breast cancer, DNA samples were obtained from 401 cases and 533 enrolled healthy controls, all of whom were Chinese women in Taiwan. Genotyping of polymorphisms of XRCC1 (Arg194Trp and Arg399Gln), OGG1 (Ser326Cys and Arg229Gln), ERCC2 Lys751Gln, ERCC4 Ser662Pro, and ERCC5 His1104Asp was performed and used to evaluate breast cancer susceptibility.

Results

Of the nonsynonymous polymorphisms, the ERCC5 1104Asp variant was significantly associated with breast cancer (odds ratio = 1.42; 95% confidence interval = 1.08–1.97), and this association was more pronounced in women with lengthy estrogen exposure. A trend toward an increased risk of developing breast cancer was observed in women who carried greater numbers of combined high-risk genotypes of BER and NER genes (P trend = .038). The synergistic effect of multiple genes on the increase of risk was significant in women with a longer period of estrogen exposure (>26 years), greater age at first full-term pregnancy (>26 years), a longer menarche-to-first full-term pregnancy interval (>11 years), and higher body mass index (>22) (all P < .05).

Conclusions

This study demonstrates that genotype polymorphisms related to DNA damage repair confer greater susceptibility to endogenous estrogen in the development of breast cancer in women.

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Acknowledgment

We thank Show-Lin Yang and Yi-Chien Mau for their help with the organization of our study. This project was supported by a research grant from the Chung Shan Medical University and Hospital and Yuanli Lee’s General Hospital (CSMU-LMC-097-003).

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Authors and Affiliations

  1. Division of General Surgery, Yuanli Lee’s General Hospital, Lee’s Medical Corporation, Miaoli, Taiwan

    Ming-Shiean Hsu MD

  2. Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan

    Jyh-Cherng Yu MD, PhD

  3. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    Hsiao-Wei Wang MSc, Chia-Ni Hsiung MSc, Pei-Ei Wu MSc, Chen-Yang Shen PhD & Chun-Wen Cheng PhD

  4. Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan

    Shou-Tung Chen MD, PhD

  5. Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan

    Shian-ling Ding PhD

  6. Taiwan Biobank, Taipei, Taiwan

    Pei-Ei Wu MSc & Chen-Yang Shen PhD

  7. Graduate Institute of Environmental Science, China Medical University, Taichung, Taiwan

    Chen-Yang Shen PhD

  8. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan

    Chun-Wen Cheng PhD

  9. Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

    Chun-Wen Cheng PhD

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  1. Ming-Shiean Hsu MD
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Correspondence to Chen-Yang Shen PhD or Chun-Wen Cheng PhD.

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Hsu, MS., Yu, JC., Wang, HW. et al. Synergistic Effects of Polymorphisms in DNA Repair Genes and Endogenous Estrogen Exposure on Female Breast Cancer Risk. Ann Surg Oncol 17, 760–771 (2010). https://doi.org/10.1245/s10434-009-0802-0

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  • DOI: https://doi.org/10.1245/s10434-009-0802-0

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