Performance of individual and joint risk stratification by an environmental risk score and a genetic risk score in a colorectal cancer screening setting
Performance of individual and joint risk stratification by an environmental risk score and a genetic risk score in a colorectal cancer screening setting
复制标题
DOI：
10.1002/ijc.32272
复制
发表时间：
2020-02-01
影响因子：
6.4
通讯作者：
Brenner, Hermann
中科院分区：
文献类型：
--
作者：
Balavarca, Yesilda;Weigl, Korbinian;Brenner, Hermann
结直肠肿瘤的早期发现可以通过对高危个体的及时干预来降低结直肠癌的疾病负担。我们的目的是评估联合环境-遗传风险评分作为早期发现晚期结直肠肿瘤（ACRN）的风险分层工具。已知的环境危险因素和高风险的遗传基因位点被总结为ACRN的风险评分在1014个合格的参与者的筛选研究。使用曲线下面积（AUC）评估单个和联合环境-遗传评分的绝对风险、相对风险和预测能力的估计值和95%置信区间（CI）。环境风险评分较高的个体显示出ACRN风险增加，与极低环境风险组相比，中度风险为3.1倍，极高风险为4.8倍。同样，具有较高遗传风险评分的个体显示出ACRN风险增加，与最低遗传风险组相比，中等风险为2.2倍，非常高风险为3.5倍。此外，联合环境-遗传评分改善了ACRN风险分层，并显示出更高的预测值（AUC = 0.64; 95%CI = 0.60-0.67），与单一环境评分（0.58; 0.55-0.62）相比具有显著差异（p = 0.0002）。环境和遗传因素的整合看起来很有希望改善针对结直肠肿瘤高风险个体的治疗。在实际筛查程序中的应用需要使用涉及结直肠癌发生的其他遗传和其他生物标志物进行优化。
Early detection of colorectal neoplasms can reduce the disease burden of colorectal cancer by timely intervention of individuals at high risk. Our aim was to evaluate a joint environmental-genetic risk score as a risk stratification tool for early detection of advanced colorectal neoplasm (ACRN). Known environmental risk factors and high-risk genetic loci were summarized into risk scores for ACRN in 1014 eligible participants of a screening study. The performances of single and joint environmental-genetic scores were evaluated with estimates and 95% confidence intervals (CI) of the absolute risk, relative risk and predictive ability using the area under the curve (AUC). Individuals with higher environmental risk scores showed increasing ACRN risk, with 3.1-fold for intermediate risk and 4.8-fold for very high risk, compared to the very low environmental risk group. Similarly, individuals with higher genetic risk scores showed increasing ACRN risk, with 2.2-fold for intermediate risk and 3.5-fold for very high risk, compared to the lowest genetic risk group. Moreover, the joint environmental-genetic score improved the ACRN risk stratification and showed higher predictive values (AUC = 0.64; 95%CI = 0.60-0.67) with substantial difference (p = 0.0002) compared to the single environmental score (0.58; 0.55-0.62). The integration of environmental and genetic factors looks promising for improving targeting individuals at high-risk of colorectal neoplasm. Applications in practical screening programs require optimization with additional genetic and other biomarkers involved in colorectal carcinogenesis.