Breast cancer has been the most common cancer diagnosed among women in Taiwan since 2003. Genetic variants account for high risks of developing breast cancer was less studied in Asian population. Many researches had discovered variant polygenic risk score (PRS) to evaluate the risk of developing breast cancer. This study aims to determine a predictive breast cancer PRS for Taiwanese populations and assess the heterogeneity in the relationships with breast cancer risk by biomarker testing, age at diagnosis, clinical and pathological stages.
The development dataset comprised 28,443 control subjects and 1,501 case subjects from Taiwan Precision Medicine Initiative (TPMI) array and breast cancer registry lists in Taichung Veterans General Hospital (TCVGH). Samples were analyzed by using breast cancer associated PGS Catalog, and significant PGSs were selected by stepwise logistic regression. The best performing PGS was yielded and 1,501 breast cancer patients were evaluated for further heterogeneity of breast cancer risk analysis.
Logistic regression results showed PGS000508 were significantly associated with breast cancer risk after multiple testing (odds ratio, 3.57; P=1.0850 E-53). Dose-response association was observed. Women in the highest quartile had a significantly increased risk compared to women in the lower quartile( odds ratio, 1.95; 95% confidence interval 1.75-2.17; P=3.54 E-34). Over 1,501 breast cancer diagnosed women stratified by PRS distribution, the highest quartile women had more advanced pathological stage (p=0.03); younger age while first diagnosis (p=0.01) and positive hormone status (p=0.03) compared to women in the lower quartile.
Our study identified PGS000508 as a risk predictor of breast cancer among Taiwanese women as well as advanced pathological stage, positive hormone status and younger age at first diagnosis.
The authors.
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All authors have declared no conflicts of interest.