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MSH2 rs2303425 Polymorphism is Associated with Early-Onset Breast Cancer in Taiwan

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Accumulated evidence indicates that the incidence of early-onset breast cancer has rapidly increased in Taiwan and other Asian compared to Western countries. The mismatch repair (MMR) pathway might be one of the crucial mechanisms of predisposition to early breast cancer. In this study, we explored whether MMR gene polymorphisms contribute to the risk of breast cancer in young women.

Methods

This was a 2-stage case–control study including 737 cases and 719 controls. After eight single nucleotide polymorphisms (SNPs) were genotyped in MMR pathway genes in the stage I study, a promising SNP, MSH2 rs2303425, was selected for validation in the stage II study. A luciferase reporter assay was used to evaluate the transcriptional activity of MSH2.

Results

Logistic regression analysis showed that individuals with the MSH2 rs2303425 C/C genotype had a significantly increased risk of breast cancer compared to those with the T/T genotype (adjusted odds ratio 2.0; 95 % confidence interval 1.1–3.8), particularly in early-onset breast cancer patients with the luminal A subtype. The luciferase assay in three cell lines indicated that the MSH2 rs2303425 T/C substitution decreased MSH2 expression, which is consistent with the finding of an association study.

Conclusions

A common variant SNP in MSH2 may contribute to the susceptibility to early-onset breast cancer functionally, particularly for the luminal A subtype.

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Acknowledgment

Supported in part by the Health and Welfare Surcharge of Tobacco Products, Ministry of Health and Wealth to the Comprehensive Cancer Center of Taipei Medical University (MOHW104-TDU-B-212-124-001), Ministry of Science and Technology (MOST 103-2314-B-038-017), and Taipei Medical University (TMU102-AE1-B03).

Disclosure

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

    Yi-Chen Hsieh PhD

  2. Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan

    Er-Chieh Cho PhD

  3. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Shih-Hsin Tu MD

  4. Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan

    Shih-Hsin Tu MD

  5. Breast Medical Center, Taipei Medical University Hospital, Taipei, Taiwan

    Shih-Hsin Tu MD & Chin-Sheng Hung MD, PhD

  6. Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan

    Chih-Hsiung Wu MD, PhD

  7. Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan

    Chin-Sheng Hung MD, PhD

  8. Department of Surgery, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan

    Mao-Chih Hsieh MD, PhD

  9. School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan

    Chien-Tien Su MD, MPH, PhD & Hung-Yi Chiou PhD

  10. Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Chien-Tien Su MD, MPH, PhD

  11. Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan

    Yun-Ru Liu PhD

  12. Graduate Institute of Medical Sciences, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

    Chia-Hwa Lee PhD & Yuan-Soon Ho PhD

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  1. Yi-Chen Hsieh PhD
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Correspondence to Hung-Yi Chiou PhD.

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Hsieh, YC., Cho, EC., Tu, SH. et al. MSH2 rs2303425 Polymorphism is Associated with Early-Onset Breast Cancer in Taiwan. Ann Surg Oncol 24, 603–610 (2017). https://doi.org/10.1245/s10434-016-5168-5

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  • DOI: https://doi.org/10.1245/s10434-016-5168-5

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