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A polygenic risk score for breast cancer risk in a Taiwanese population

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

Multiple common variants identified by genome-wide association studies showed limited evidence of the risk of breast cancer in Taiwan. In this study, we analyzed the breast cancer risk in relation to 13 individual single-nucleotide polymorphisms (SNPs) identified by a GWAS in an Asian population.

Methods

In total, 446 breast cancer patients and 514 healthy controls were recruited for this case–control study. In addition, we developed a polygenic risk score (PRS) including those variants significantly associated with breast cancer risk, and also evaluated the contribution of PRS and clinical risk factors to breast cancer using receiver operating characteristic curve (AUC).

Results

Logistic regression results showed that nine individual SNPs were significantly associated with breast cancer risk after multiple testing. Among all SNPs, six variants, namely FGFR2 (rs2981582), HCN1 (rs981782), MAP3K1 (rs889312), TOX3 (rs3803662), ZNF365 (rs10822013), and RAD51B (rs3784099), were selected to create PRS model. A dose–response association was observed between breast cancer risk and the PRS. Women in the highest quartile of PRS had a significantly increased risk compared to women in the lowest quartile (odds ratio 2.26; 95% confidence interval 1.51–3.38). The AUC for a model which contained the PRS in addition to clinical risk factors was 66.52%, whereas that for a model which with established risk factors only was 63.38%.

Conclusions

Our data identified a genetic risk predictor of breast cancer in Taiwanese population and suggest that risk models including PRS and clinical risk factors are useful in discriminating women at high risk of breast cancer from those at low risk.

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Acknowledgements

This study was supported by the Health and Welfare Surcharge of Tobacco Products, Ministry of Health and Welfare to the Comprehensive Cancer Center of Taipei Medical University (MOHW105-TDU-B-212-134001), Taipei Medical University Hospital (103TMU-TMUH-09), Taipei Medical University (TMU102-AE1-B03), and the Top University Project- Cancer Translational Center of Taipei Medical University.

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    Authors and Affiliations

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

      Yi-Chen Hsieh

    2. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 252 Wu-Hsing St., Taipei, Taiwan

      Shih-Hsin Tu & Chin-Sheng Hung

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

      Shih-Hsin Tu & Chin-Sheng Hung

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

      Shih-Hsin Tu & Chin-Sheng Hung

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

      Chien-Tien Su

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

      Chien-Tien Su & Shiyng-Yu Lin

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

      Er-Chieh Cho

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

      Chih-Hsiung Wu

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

      Mao-Chih Hsieh

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

      Yun-Ru Liu

    11. School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wu-Hsing St., Taipei, Taiwan

      Hung-Yi Chiou

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    Correspondence to Chin-Sheng Hung or Hung-Yi Chiou.

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    The authors declare that they have no conflict of interest.

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    Chin-Sheng Hung and Hung-Yi Chiou contributed equally to this study.

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    Hsieh, YC., Tu, SH., Su, CT. et al. A polygenic risk score for breast cancer risk in a Taiwanese population. Breast Cancer Res Treat 163, 131–138 (2017). https://doi.org/10.1007/s10549-017-4144-5

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    • DOI: https://doi.org/10.1007/s10549-017-4144-5

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