Before SNP-based risk can be incorporated in colorectal cancer (CRC) screening, the ability of these SNPs to estimate CRC risk for persons with and without a family history of CRC, and the screening implications need to be determined. We estimated the association with CRC of a 45 SNP-based risk using 1181 cases and 999 controls, and its correlation with CRC risk predicted from detailed family history. We estimated the predicted change in the distribution across predefined risk categories, and implications for recommended screening commencement age, from adding SNP-based risk to family history. The inter-quintile risk ratio for colorectal cancer risk of the SNP-based risk was 3.28 (95% CI 2.54–4.22). SNP-based and family history-based risks were not correlated (r = 0.02). For persons with no first-degree relatives with CRC, screening could commence 4 years earlier for women (5 years for men) in the highest quintile of SNP-based risk. For persons with two first-degree relatives with CRC, screening could commence 16 years earlier for men and women in the highest quintile, and 7 years earlier for the lowest quintile. This 45 SNP panel in conjunction with family history, can identify people who could benefit from earlier screening. Risk reclassification by 45 SNPs could inform targeted screening for CRC prevention, particularly in clinical genetics settings when mutations in high-risk genes cannot be identified. Yet to be determined is cost-effectiveness, resources requirements, community, patient and clinician acceptance, and feasibility with potentially ethical, legal and insurance implications.

中文翻译：

---

已知的易感性 SNP 能够预测有或无家族史的人患结直肠癌的风险。


在将基于 SNP 的风险纳入结直肠癌 (CRC) 筛查之前，需要确定这些 SNP 评估有或没有 CRC 家族史的人的 CRC 风险的能力，以及筛查的影响。我们使用 1181 例病例和 999 例对照评估了 45 个基于 SNP 的风险与 CRC 的关联，及其与根据详细家族史预测的 CRC 风险的相关性。我们估计了预定义风险类别分布的预测变化，以及将基于 SNP 的风险添加到家族史中对建议筛查开始年龄的影响。基于 SNP 的风险的结直肠癌风险的五分位间风险比为 3.28 (95% CI 2.54–4.22)。基于 SNP 的风险和基于家族史的风险不相关 ( r = 0.02)。对于没有一级亲属患有 CRC 的人，在基于 SNP 的风险最高的五分位数中，女性可以提前 4 年（男性 5 年）开始筛查。对于有两名一级亲属患有 CRC 的人，最高五分之一的男性和女性可以提前 16 年开始筛查，最低五分之一的男性和女性可以提前 7 年开始筛查。这个 45 SNP 组合与家族史相结合，可以识别出可以从早期筛查中受益的人。 45 个 SNP 的风险重新分类可以为 CRC 预防的针对性筛查提供信息，特别是在无法识别高风险基因突变的临床遗传学环境中。尚待确定的是成本效益、资源需求、社区、患者和临床医生的接受度，以及潜在的伦理、法律和保险影响的可行性。