Journal Article

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

Tsai, I.-Chen, Lin, Guan-Cheng, Lin, Yi-Hsuan, Lum, Chih Yean, Hsiao, Tzu-Hung, Hung, Chih-Chiang

2025

Overview

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-Asian populations, creating a notable gap in our understanding of their effects in Asian communities.•Our research identified PGS000508 as a crucial polygenic risk score (PRS) that effectively predicts breast cancer risk specifically in Taiwanese women, with our findings revealing that higher PGS000508 scores correlate significantly with earlier age of breast cancer onset among affected individuals.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adult / Age composition / Aged / Breast cancer / Breast cancer risk / Breast Neoplasms - epidemiology / Breast Neoplasms - genetics / Case-Control Studies / Cohort Studies / Early detection / Epidemiology / Female / Genetic diversity / Genetic Predisposition to Disease / Genetic Risk Score / Genomes / Genotype & phenotype / Health risks / Hospitals / Humans / Medical screening / Middle Aged / Mortality / Multifactorial Inheritance / Mutation / PGS000508 / Population genetics / Population studies / Precision medicine / Quality control / Quality standards / Regression analysis / Risk Assessment / Risk Factors / Standard deviation / Taiwan - epidemiology / Taiwanese women / Womens health