林奇综合征
医学
内科学
肿瘤科
结直肠癌
人口
MSH6型
危险系数
比例危险模型
癌症
置信区间
DNA错配修复
环境卫生
作者
Núria Dueñas,Hannah Klinkhammer,Núria Bonifaci,Isabel Spier,Andreas Mayr,Emadeldin Hassanin,Anna Díez-Villanueva,Vı́ctor Moreno,Marta Pineda,Carlo Maj,Gabriel Capellá,Stefan Aretz,Joan Brunet
标识
DOI:10.1136/jmg-2023-109344
摘要
Polygenic risk scores (PRSs) have been used to stratify colorectal cancer (CRC) risk in the general population, whereas its role in Lynch syndrome (LS), the most common type of hereditary CRC, is still conflicting. We aimed to assess the ability of PRS to refine CRC risk prediction in European-descendant individuals with LS.1465 individuals with LS (557 MLH1, 517 MSH2/EPCAM, 299 MSH6 and 92 PMS2) and 5656 CRC-free population-based controls from two independent cohorts were included. A 91-SNP PRS was applied. A Cox proportional hazard regression model with 'family' as a random effect and a logistic regression analysis, followed by a meta-analysis combining both cohorts were conducted.Overall, we did not observe a statistically significant association between PRS and CRC risk in the entire cohort. Nevertheless, PRS was significantly associated with a slightly increased risk of CRC or advanced adenoma (AA), in those with CRC diagnosed <50 years and in individuals with multiple CRCs or AAs diagnosed <60 years.The PRS may slightly influence CRC risk in individuals with LS in particular in more extreme phenotypes such as early-onset disease. However, the study design and recruitment strategy strongly influence the results of PRS studies. A separate analysis by genes and its combination with other genetic and non-genetic risk factors will help refine its role as a risk modifier in LS.
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