Objective: To evaluate the effectiveness of a risk-adapted colorectal cancer screening strategy constructed utilizing genetic and environmental risk score (ERS). Methods: A polygenic risk score (PRS) was constructed based on 20 previously published single nucleotide polymorphisms for colorectal cancer in East Asian populations, using 2 160 samples with MassARRAY test results from a multicenter randomized controlled trial of colorectal cancer screening in China. The ERS was calculated using the Asia-Pacific Colorectal Screening Score system. Logistic regression was used to analyze the association between PRS alone and PRS combined with ERS and colorectal neoplasms risk, respectively. We also designed a risk-adapted screening strategy based on PRS and ERS (high-risk participants undergo a single colonoscopy, low-risk participants undergo an annual fecal immunochemical test, and those with positive results undergo further diagnostic colonoscopy) and compared its effectiveness with the all-acceptance colonoscopy strategy. Results: The high PRS group had a 26% increased risk of colorectal neoplasms compared with the low PRS group (OR=1.26, 95%CI: 1.03-1.54, P=0.026). Participants with the highest PRS and ERS were 3.03 times more likely to develop advanced colorectal neoplasms than those with the lowest score (95%CI: 1.87-4.90, P<0.001). As the risk-adapted screening simulation reached the third round, the detection rate of the PRS combined with ERS strategy was not statistically different from the all-acceptance colonoscopy strategy (8.79% vs. 10.46%, P=0.075) and had a higher positive predictive value (14.11% vs. 10.46%, P<0.001) and lower number of colonoscopies per advanced neoplasms detected (7.1 vs. 9.6, P<0.001). Conclusion: The risk-adapted screening strategy combining PRS and ERS helps achieve population risk stratification and better effectiveness than the traditional colonoscopy-based screening strategy.
目的： 评价利用遗传与环境危险因素构建的结直肠肿瘤风险评分的人群高危分层效果及其在分级筛查中的应用效果。 方法： 基于一项全国多中心结直肠癌筛查随机对照研究，纳入2 160例接受结肠镜检查的研究对象。采用MassARRAY技术检测20个结直肠癌相关的遗传易感位点并构建遗传风险评分。个体环境风险评分采用亚太结直肠筛查评分系统计算。使用logistic回归分别评估遗传风险单独和遗传联合环境风险与结直肠肿瘤之间的关联。构建基于遗传和/或环境风险评分的分级筛查方案（即高风险者接受单次结肠镜筛查，低风险者接受每年一次的定量粪便免疫化学检测，其结果阳性者接受结肠镜检查），并与全部接受结肠镜方案进行效果比较。 结果： 与低遗传风险评分组相比，高遗传风险评分组发生结直肠肿瘤的风险增加了26%（OR=1.26，95%CI：1.03~1.54，P=0.026）。遗传和环境风险评分均最高的研究对象患进展期肿瘤（包括结直肠癌、进展期腺瘤和进展期锯齿状息肉）的风险是两评分均最低研究对象的3.03倍（95%CI：1.87~4.90，P<0.001）。多轮筛查效果评价方面，当进行到第3轮筛查时，基于遗传联合环境风险评分构建的分级筛查方案，其进展期肿瘤累计检出率与全部接受结肠镜检查方案差异无统计学意义（8.79% vs. 10.46%，P=0.075），阳性预测值更高（14.11% vs. 10.46%，P<0.001），每检出1例进展期肿瘤所需的结肠镜检查数更低（7.1 vs. 9.6，P<0.001）。 结论： 与基于结肠镜的传统筛查方法相比，联合遗传和环境风险评分的分级筛查方案有助于实现人群风险分层，取得较好的筛查效果。.