Background & Aims

Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of CRC, based on lifestyle and environmental factors and genetic variants, and to identify an optimal age to begin screening.

Methods

We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005. Half of the participants were used to develop the risk determination model and the other half were used to evaluate the discriminatory accuracy (validation set). Models of CRC risk were created based on family history, 19 lifestyle and environmental factors (E-score), and 63 CRC-associated single-nucleotide polymorphisms identified in genome-wide association studies (G-score). We evaluated the discriminatory accuracy of the models by calculating area under the receiver operating characteristic curve (AUC) values, adjusting for study, age, and endoscopy findings for the validation set. We used the models to project the 10-year absolute risk of CRC for a given risk profile and recommend ages to begin screening, in comparison to CRC risk for an average individual at 50 years of age, using external population incidence rates for non-Hispanic whites from the Surveillance, Epidemiology, and End Results Program registry.

Results

In our models, E-score and G-score each determined risk of CRC with greater accuracy than family history. A model that combined both scores and family history estimated CRC risk with an AUC value of 0.63 (95% CI, 0.62–0.64) for men and 0.62 (95% CI, 0.61–0.63) for women; AUC values based on only family history ranged from 0.53 to 0.54 and those based only E-score or G-score ranged from 0.59 to 0.60. Although screening is recommended to begin at age 50 years for individuals with no family history of CRC, starting ages calculated based on combined E-score and G-score differed by 12 years for men and 14 for women, for individuals with the highest vs the lowest 10% of risk.

Conclusions

We used data from 2 large international consortia to develop CRC risk calculation models that included genetic and environmental factors along with family history. These determine risk of CRC and starting ages for screening with greater accuracy than the family history only model, which is based on the current screening guideline. These scoring systems might serve as a first step toward developing individualized CRC prevention strategies.

中文翻译：

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根据生活方式，环境和遗传因素确定大肠癌的风险和筛查的起始年龄

背景与目标

结肠直肠癌（CRC）筛查的指南基于家族史，但未考虑生活方式，环境或遗传风险因素。我们开发了基于生活方式和环境因素以及遗传变异来确定CRC风险的模型，并确定了开始筛查的最佳年龄。

方法

我们从1992年至2005年收集了9748例CRC病例和10,590名对照的大肠癌遗传学和流行病学以及大肠跨学科研究的数据。一半的参与者用于建立风险确定模型，另一半用于评估歧视性准确性（验证集）。根据家族史，19种生活方式和环境因素（E评分）以及在全基因组关联研究（G评分）中发现的63种CRC关联的单核苷酸多态性，创建了CRC风险模型。我们通过计算接收器工作特征曲线（AUC）值下的面积，针对验证集调整研究，年龄和内窥镜检查结果，评估了模型的区分准确性。

结果

在我们的模型中，E评分和G评分均比家族病史更准确地确定了CRC的风险。结合得分和家族史的模型估计出男性的CRC风险为AUC值为0.63（95％CI，0.62-0.64），女性的AUC值为0.62（95％CI，0.61-0.63）。仅基于家族史的AUC值范围为0.53至0.54，仅基于E评分或G评分的AUC值范围为0.59至0.60。尽管建议对没有CRC家族史的个体从50岁开始筛查，但对于Es和G最高的个体，根据E分数和G分数相加得出的起始年龄，男性分别为12岁，女性为14岁。风险最低10％。

结论

我们使用来自2个大型国际财团的数据来开发CRC风险计算模型，其中包括遗传和环境因素以及家族病史。这些决定了CRC的风险和筛查的起始年龄，其准确性要高于仅基于家族史的筛查模型，后者基于当前的筛查指南。这些评分系统可能是迈向制定个性化CRC预防策略的第一步。