Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
Cancer Prev Res (Phila). 2021 Jun;14(6):649-658. doi: 10.1158/1940-6207.CAPR-20-0576. Epub 2021 Mar 2.
Genetic and lifestyle factors contribute to colorectal cancer risk. We investigated their individual and joint associations with various stages of colorectal carcinogenesis. We assessed associations of a polygenic risk score (PRS) and a healthy lifestyle score (HLS) with presence of nonadvanced adenomas and advanced neoplasms among 2,585 participants of screening colonoscopy from Germany. The PRS and HLS individually showed only weak associations with presence of nonadvanced adenomas; stronger associations were observed with advanced neoplasms (ORs, 95% CI, for highest vs. lowest risk tertile: PRS 2.27, 1.78-2.88; HLS 1.96, 1.53-2.51). The PRS was associated with higher odds of advanced neoplasms among carriers of any neoplasms (1.65, 1.23-2.22). Subjects in the highest risk tertile (vs. lowest tertile) of both scores had higher risks for nonadvanced adenomas (1.77, 1.09-2.86), for advanced neoplasms (3.95, 2.53-6.16) and, among carriers of any neoplasms, for advanced versus nonadvanced neoplasms (2.26, 1.31-3.92). Both scores were individually associated with increased risk of nonadvanced adenomas and, much more pronounced, advanced neoplasms. The similarly strong association in relative terms across all levels of genetic risk implies that a healthy lifestyle may be particularly beneficial in those at highest genetic risk, given that the same relative risk reduction in this group would imply a stronger absolute risk reduction. Genetic factors may be of particular relevance for the transition of nonadvanced to advanced adenomas. PREVENTION RELEVANCE: Genetic factors have strong impact on the risk of colorectal neoplasms, which may be reduced by healthy lifestyle. Similarly strong associations in relative terms across all levels of genetic risk imply that a healthy lifestyle may be beneficial due to higher absolute risk reduction in those at highest genetic risk.
遗传和生活方式因素会增加结直肠癌的风险。我们研究了它们各自以及联合与结直肠癌变各个阶段的关系。我们评估了多基因风险评分（PRS）和健康生活方式评分（HLS）与德国 2585 名筛查结肠镜参与者中非晚期腺瘤和晚期肿瘤存在的相关性。PRS 和 HLS 与非晚期腺瘤的存在仅有微弱的相关性；而与晚期肿瘤的相关性更强（OR，95%CI，最高与最低风险三分位数：PRS 2.27，1.78-2.88；HLS 1.96，1.53-2.51）。PRS 与携带任何肿瘤者的晚期肿瘤发生几率升高相关（1.65，1.23-2.22）。PRS 和 HLS 得分最高组（vs. 最低组）的受试者发生非晚期腺瘤的风险更高（1.77，1.09-2.86），发生晚期肿瘤的风险更高（3.95，2.53-6.16），而且在携带任何肿瘤者中，发生晚期腺瘤而非非晚期腺瘤的风险也更高（2.26，1.31-3.92）。PRS 和 HLS 单独与非晚期腺瘤风险升高相关，而且与晚期肿瘤的相关性要强得多。在所有遗传风险水平上，PRS 和 HLS 的相对风险具有相似的强相关性，这意味着在遗传风险最高的人群中，健康的生活方式可能特别有益，因为在该人群中，相同的相对风险降低意味着更强的绝对风险降低。遗传因素可能与非晚期腺瘤向晚期腺瘤的转变特别相关。预防相关性：遗传因素对结直肠肿瘤的风险有很大影响，而健康的生活方式可能会降低这种风险。在所有遗传风险水平上，PRS 和 HLS 的相对风险具有相似的强相关性，这意味着在遗传风险最高的人群中，健康的生活方式可能有益，因为在这些人群中，绝对风险降低幅度更大。
