A polygenic risk score for breast cancer risk in a Taiwanese population
A polygenic risk score for breast cancer risk in a Taiwanese population
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DOI：
10.1007/s10549-017-4144-5
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发表时间：
2017-05-01
影响因子：
3.8
通讯作者：
Chiou, Hung-Yi
中科院分区：
文献类型：
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作者：
Hsieh, Yi-Chen;Tu, Shih-Hsin;Chiou, Hung-Yi
全基因组关联研究确定的多个常见变异表明，台湾患乳腺癌风险的证据有限。在这项研究中，我们分析了亚洲人群中13个单核苷酸多态(SNPs)与乳腺癌风险的关系。总共有446名乳腺癌患者和514名健康对照参加了这项病例对照研究。此外，我们开发了一个多基因风险评分(PRS)，包括那些与乳腺癌风险显著相关的变异，并使用接受者操作特征曲线(AUC)评估了多基因风险评分和临床风险因素对乳腺癌的贡献。Logistic回归分析结果显示，经多次检验，9个单核苷酸多态与乳腺癌风险显著相关。在所有SNP中，选择了FGFR2(Rs2981582)、HCN1(Rs981782)、MAP3K1(Rs889312)、TOX3(Rs3803662)、ZNF365(Rs10822013)和RAD51B(Rs3784099)6个变异体来建立PRS模型。观察到乳腺癌风险和PR之间存在剂量-反应关系。与处于最低四分位数的女性相比，具有最高四分位数的女性风险显著增加(优势比2.26；95%可信区间1.51-3.38)。除了临床危险因素外，包含有乳腺癌危险因素的模型的AUC为66.52%，而仅包含已建立的危险因素的模型的AUC为63.38%。我们的数据确定了台湾人群中乳腺癌的遗传风险预测因子，并提示包括危险因素和临床危险因素在内的风险模型在区分乳腺癌高危女性和低危女性方面是有用的。
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.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).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%.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.