Developing an optimal stratification model for colorectal cancer screening and reducing racial disparities in multi-center population-based studies

作者：Jianbo Tian, Ming Zhang, Fuwei Zhang, Kai Gao, Zequn Lu, Yimin Cai, Can Chen, Caibo Ning, Y.X. Li, Sangni Qian, Hao Bai, Yizhuo Liu, Heng Zhang, Shuoni Chen, Xiangpan Li, Yongchang Wei, Bin Li, Ying Zhu, Jinhua Yang, Mingjuan Jin, Xiaoping Miao, Kun Chen · 发表于：Genome Medicine · 年份：2024 · DOI：10.1186/s13073-024-01355-y · 被引用次数：13 · 研究领域：Colorectal Cancer Screening and Detection、Global Cancer Incidence and Screening、Genetic factors in colorectal cancer

Abstract Background Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population. Methods To develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS 148 ); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS 183 ); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRS Genomewide ). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants. Results Three trans-ancestry PRSs achieved moderately improved predictive perfo...