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.

中文翻译：

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结肠镜检查参与者的遗传风险和健康生活方式评分与结直肠肿瘤的个体和联合关联

遗传和生活方式因素会增加结直肠癌的风险。我们调查了他们与结直肠癌发生不同阶段的个体和联合关联。我们评估了来自德国的 2,585 名筛查结肠镜检查参与者的多基因风险评分 (PRS) 和健康生活方式评分 (HLS) 与非晚期腺瘤和晚期肿瘤存在的关联。PRS 和 HLS 分别仅显示与非晚期腺瘤存在的弱关联；观察到与晚期肿瘤有更强的关联（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 与任何肿瘤携带者中晚期肿瘤发生率较高有关 (1.65, 1.23–2.22)。处于最高风险三分位数的受试者（vs. 两个分数的最低三分位数）对于非晚期腺瘤（1.77, 1.09-2.86），晚期肿瘤（3.95, 2.53-6.16）以及在任何肿瘤的携带者中，晚期与非晚期肿瘤（2.26, 1.31-3.92）的风险较高. 这两个分数都与非晚期腺瘤的风险增加有关，更明显的是，晚期肿瘤的风险增加。在所有遗传风险水平的相对方面，类似的强关联意味着健康的生活方式可能对那些遗传风险最高的人特别有益，因为该组中相同的相对风险降低将意味着更强烈的绝对风险降低。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，这可以通过健康的生活方式来减少。在所有遗传风险水平的相对术语中，类似的强关联意味着健康的生活方式可能是有益的，因为在最高遗传风险的人中绝对风险降低更高。