FP7 Outputs
Published December 8, 2016 | Version v1
Journal article Open

Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry

Creators

  • 1. Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
  • 2. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • 3. Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
  • 4. Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
  • 5. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
  • 6. Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
  • 7. International Agency for Research on Cancer, Lyon, France
  • 8. Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
  • 9. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
  • 10. Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
  • 11. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
  • 12. Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK
  • 13. Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
  • 14. National Cancer Institute, Bangkok, Thailand
  • 15. School of Public Health, China Medical University, Taichung, Taiwan
  • 16. Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia
  • 17. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
  • 18. Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia
  • 19. Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada
  • 20. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 21. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea

Description

Background: Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry.

Methods: We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk.

Results: We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P < 0.05. Compared with women in the middle quintile of the PRS, women in the top 1% group had a 2.70-fold elevated risk of breast cancer (95% CI: 2.15–3.40). The risk prediction model with the PRS had an area under the receiver operating characteristic curve of 0.606. The lifetime risk of breast cancer for Shanghai Chinese women in the lowest and highest 1% of the PRS was 1.35% and 10.06%, respectively.

Conclusion: Approximately one-half of GWAS-identified breast cancer risk variants can be directly replicated in East Asian women. Collectively, common genetic variants are important predictors for breast cancer risk. Using common genetic variants for breast cancer could help identify women at high risk of breast cancer.

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Additional details

Funding

European Commission
COGS – Collaborative Oncological Gene-environment Study 223175