Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Nat Commun. 2021 Feb 12;12(1):970. doi: 10.1038/s41467-021-21288-z.
Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969 cases, 359,802 controls). Within cohorts, each PRS is evaluated in multivariable logistic regression models against all other cancer types. Results are then meta-analyzed across cohorts. Ten positive and one inverse cross-cancer associations are found after multiple testing correction. Two pairs show bidirectional associations; the melanoma PRS is positively associated with oral cavity/pharyngeal cancer and vice versa, whereas the lung cancer PRS is positively associated with oral cavity/pharyngeal cancer, and the oral cavity/pharyngeal cancer PRS is inversely associated with lung cancer. Overall, we validate known, and uncover previously unreported, patterns of pleiotropy that have the potential to inform investigations of risk prediction, shared etiology, and precision cancer prevention strategies.
即使是不同的癌症类型也具有共同的生物学特征。在这里，我们研究了来自遗传流行病学研究成人健康与衰老队列（16012 例病例，50552 例对照）和英国生物银行（48969 例病例，359802 例对照）的欧洲血统个体中 16 种癌症的多基因风险评分（PRS）特异性多效性。在队列内，每个 PRS 在多变量逻辑回归模型中针对所有其他癌症类型进行评估。然后对队列进行荟萃分析。在经过多次测试校正后，发现了 10 个阳性和 1 个反向跨癌关联。两对显示出双向关联；黑色素瘤 PRS 与口腔/咽癌呈正相关，反之亦然，而肺癌 PRS 与口腔/咽癌呈正相关，口腔/咽癌 PRS 与肺癌呈负相关。总的来说，我们验证了已知的、并揭示了以前未报告的多效性模式，这些模式有可能为风险预测、共同病因学和精准癌症预防策略的研究提供信息。
