Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Victoria, Australia.
Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Victoria, Australia.
JNCI Cancer Spectr. 2021 Mar 8;5(2). doi: 10.1093/jncics/pkab022. eCollection 2021 Apr.
It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes-people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 , 314 , 126 , 71 , and 22 ) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided >.05). The hazard ratio per standard deviation of the PRS for colorectal cancer was 0.97 (95% confidence interval = 0.88 to 1.06; 2-sided =.51). Whereas PRSs are predictive of colorectal cancer in the general population, they do not predict Lynch syndrome colorectal cancer.
尚不清楚预测结直肠癌的多基因风险评分（PRS）是否可用于预测 DNA 错配修复基因种系致病性变异患者的结直肠癌——即林奇综合征患者。我们针对来自结肠癌家族登记处的 826 名欧洲血统的 DNA 错配修复基因致病性变异携带者（293、314、126、71 和 22），测试了一个包含 107 个与欧洲人群结直肠癌相关的已确立单核苷酸多态性的 PRS，其中 504 人患有结直肠癌。PRS 与结直肠癌风险之间没有关联的证据，不论突变的是哪种 DNA 错配修复基因，或性别（所有双侧>.05）。PRS 每标准偏差的结直肠癌风险比为 0.97（95%置信区间=0.88 至 1.06；双侧=.51）。虽然 PRS 可预测一般人群中的结直肠癌，但不能预测林奇综合征相关的结直肠癌。
