Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank.

IF 15.8 1区医学 Q1 Medicine

PLoS Medicine Pub Date : 2025-02-28 eCollection Date: 2025-02-01 DOI:10.1371/journal.pmed.1004534

Meng Zhu, Xia Zhu, Yuting Han, Zhimin Ma, Chen Ji, Tianpei Wang, Caiwang Yan, Ci Song, Canqing Yu, Dianjianyi Sun, Yue Jiang, Jiaping Chen, Ling Yang, Yiping Chen, Huaidong Du, Robin Walters, Iona Y Millwood, Juncheng Dai, Hongxia Ma, Zhengdong Zhang, Zhengming Chen, Zhibin Hu, Jun Lv, Guangfu Jin, Liming Li, Hongbing Shen

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引用次数: 0

Abstract

Background: Polygenic risk scores (PRSs) have been extensively developed for cancer risk prediction in European populations, but their effectiveness in the Chinese population remains uncertain.

Methods and findings: We constructed 80 PRSs for the 13 most common cancers using seven schemes and evaluated these PRSs in 100,219 participants from the China Kadoorie Biobank (CKB). The optimal PRSs with the highest discriminatory ability were used to define genetic risk, and their site-specific and cross-cancer associations were assessed. We modeled 10-year absolute risk trajectories for each cancer across risk strata defined by PRSs and modifiable risk scores and quantified the explained relative risk (ERR) of PRSs with modifiable risk factors for different cancers. More than 60% (50/80) of the PRSs demonstrated significant associations with the corresponding cancer outcomes. Optimal PRSs for nine common cancers were identified, with each standard deviation increase significantly associated with corresponding cancer risk (hazard ratios (HRs) ranging from 1.20 to 1.76). Compared with participants at low genetic risk and reduced modifiable risk scores, those with high genetic risk and elevated modifiable risk scores had the highest risk of incident cancer, with HRs ranging from 1.97 (95% confidence interval (CI): 1.11-3.48 for cervical cancer, P = 0.020) to 8.26 (95% CI: 1.92-35.46 for prostate cancer, P = 0.005). We observed nine significant cross-cancer associations for PRSs and found the integration of PRSs significantly increased the prediction accuracy for most cancers. The PRSs contributed 2.6%-20.3%, while modifiable risk factors explained 2.3%-16.7% of the ERR in the Chinese population.

Conclusions: The integration of existing evidence has facilitated the development of PRSs associated with nine common cancer risks in the Chinese population, potentially improving clinical risk assessment.

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背景：多基因风险评分（PRSs）已在欧洲人群中广泛用于癌症风险预测，但其在中国人群中的有效性仍不确定：我们采用七种方案为 13 种最常见的癌症构建了 80 个多基因风险评分，并在中国嘉道理生物库（CKB）的 100 219 名参与者中对这些多基因风险评分进行了评估。判别能力最高的最优PRS被用来定义遗传风险，并评估了它们与特定部位和交叉癌症的关联。我们模拟了每种癌症在PRS和可改变风险评分所定义的风险分层中的10年绝对风险轨迹，并量化了PRS与不同癌症的可改变风险因素的解释相对风险（ERR）。超过 60% 的 PRSs（50/80）与相应的癌症结果有显著关联。针对九种常见癌症确定了最佳的 PRS，每个标准差的增加都与相应的癌症风险显著相关（危险比（HRs）从 1.20 到 1.76 不等）。与遗传风险低且可调整风险评分降低的参与者相比，遗传风险高且可调整风险评分升高的参与者罹患癌症的风险最高，HR 值从宫颈癌的 1.97（95% 置信区间 (CI)：1.11-3.48，P = 0.020）到前列腺癌的 8.26（95% 置信区间 (CI)：1.92-35.46，P = 0.005）不等。我们观察到 PRSs 与 9 种癌症有明显的交叉关联，并发现整合 PRSs 能显著提高大多数癌症的预测准确率。在中国人群的ERR中，PRS占2.6%-20.3%，而可改变的风险因素占2.3%-16.7%：现有证据的整合促进了与中国人群九种常见癌症风险相关的PRS的发展，从而有可能改善临床风险评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PLoS Medicine MEDICINE, GENERAL & INTERNAL-

CiteScore

17.60

自引率

0.60%

发文量

227

审稿时长

4-8 weeks

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