Utilizing polygenic risk score for breast cancer risk prediction in a Taiwanese population

• Published in: Cancer epidemiology 2025-02, Vol.94, p.102701, Article 102701
• Main Authors: Lin, Yi-Hsuan, Hung, Chih-Chiang, Lin, Guan-Cheng, Tsai, I.-Chen, Lum, Chih Yean, Hsiao, Tzu-Hung
• Format: Article
• Language: English
• Subjects: Breast cancer risk; Early detection; Epidemiology; PGS000508; Taiwanese women
• ISSN: 1877-7821; 1877-783X; 1877-783X
• DOI: 10.1016/j.canep.2024.102701

Breast cancer has been the most frequently diagnosed cancer among women in Taiwan since 2003. While genetic variants play a significant role in the elevated risk of breast cancer, their implications have been less explored within Asian populations. Variant-based polygenic risk scores (PRS) have emerged as valuable tools for assessing the likelihood of developing breast cancer. In light of this, we attempted to establish a predictive breast cancer PRS tailored specifically for the Taiwanese population. The cohort analyzed in this study comprised 28,443 control subjects and 1501 breast cancer cases. These individuals were sourced from the Taiwan Precision Medicine Initiative (TPMI) array and the breast cancer registry lists at Taichung Veterans General Hospital (TCVGH). Utilizing the breast cancer-associated Polygenic Score (PGS) Catalog, we employed logistic regression to identify the most effective PRS for predicting breast cancer risk. Subsequently, we subjected the cohort of 1501 breast cancer patients to further analysis to investigate potential heterogeneity in breast cancer risk. The Polygenic Score ID PGS000508 demonstrated a significant association with breast cancer risk in Taiwanese women with a 1.498-fold increase in cancer risk(OR = 1.498, 95 % CI(1.431–1.567, p=5.38×10^-68). Individuals in the highest quartile exhibited a substantially elevated risk compared to those in the lowest quartile, with an odds ratio (OR) of 3.11 (95 % CI: 2.70–3.59; p=1.15×10^-55). In a cohort of 1501 breast cancer cases stratified by PRS distribution, women in the highest quartile were diagnosed at a significantly younger age (p=0.003) compared to those in the lowest quartile. However, no significant differences were observed between PRS quartiles in relation to clinical stage (p=0.274), pathological stage (p=0.647), or tumor subtype distribution (p=0.244). In our study, we pinpointed PGS000508 as a significant predictive factor for breast cancer risk in Taiwanese women. Furthermore, we found that a higher PGS000508 score was associated with younger age at the time of first diagnosis among the breast cancer cases examined. •Breast cancer has maintained its position as the most common cancer diagnosis among Taiwanese women since 2003, highlighting a significant public health concern in the region.•While genetic factors are known to substantially influence breast cancer risk, research on these genetic variants and their impacts has been predominantly focused on non-Asi