title: A polygenic risk score for breast cancer risk in a Taiwanese population.
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.
authors.affiliation: Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Hsieh
authors.affiliation: Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 252 Wu-Hsing St., Taipei, Taiwan.|Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.|Breast Medical Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Tu
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.|Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chien-Tien
authors.initials: CT
authors.lastname: Su
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Er-Chieh
authors.initials: EC
authors.lastname: Cho
authors.affiliation: Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Surgery, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Mao-Chih
authors.initials: MC
authors.lastname: Hsieh
authors.affiliation: Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shiyng-Yu
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Liu
authors.affiliation: Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 252 Wu-Hsing St., Taipei, Taiwan. hungcs@tmu.edu.tw.|Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan. hungcs@tmu.edu.tw.|Breast Medical Center, Taipei Medical University Hospital, Taipei, Taiwan. hungcs@tmu.edu.tw.
authors.forename: Chin-Sheng
authors.initials: CS
authors.lastname: Hung
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wu-Hsing St., Taipei, Taiwan. hychiou@tmu.edu.tw.
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan; D055815:Young Adult
keywords: Breast cancer; Common variants; Polygenic risk score; Risk prediction