Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Division of Biomedical Statistics & Informatics, Mayo Clinic, Rochester, Minnesota.
Cancer Epidemiol Biomarkers Prev. 2020 Aug;29(8):1570-1576. doi: 10.1158/1055-9965.EPI-19-1598. Epub 2020 May 28.
Emerging colorectal cancer trends demonstrate increased incidence and mortality in younger populations, prompting consideration of average-risk colorectal cancer screening initiation at age 45 versus 50 years. However, screening test performance characteristics in adults 45-49 years have been minimally described. To inform the biologic rationale for multi-target stool DNA (mt-sDNA) screening in younger patients, we analyzed and compared tissue levels of methylation () and mutation () markers included in the FDA-approved, mt-sDNA assay (Cologuard; Exact Sciences Corporation).
Within 40-44, 45-49, and 50-64 year age groups, archived colorectal tissue specimens were identified for 211 sporadic colorectal cancer cases, 123 advanced precancerous lesions (APLs; adenomas >1 cm, high-grade dysplasia, ≥25% villous morphology, or sessile serrated polyp; 45-49 and 50-64 age groups only), and 204 histologically normal controls. Following DNA extraction, , and were quantified using QuARTS assays, relative to (reference gene).
None of the molecular marker concentrations were significantly associated with age ( > 0.05 for all comparisons), with the exception of concentration in APL samples (higher in older vs. younger cases; = 0.008). However, levels were also statistically higher in APL case versus normal control samples in both the 45-49 ( < 0.0001) and 50-64 ( < 0.0001) year age groups.
Overall, these findings support the potential for earlier onset of average-risk colorectal cancer screening with the mt-sDNA assay.
These novel data address an identified knowledge gap and strengthen the biologic basis for earlier-onset, average-risk screening with the mt-sDNA assay.
新兴的结直肠癌趋势表明，年轻人群的发病率和死亡率有所增加，这促使人们考虑将平均风险结直肠癌筛查的起始年龄从 50 岁提前到 45 岁。然而，对于 45-49 岁成年人的筛查测试性能特征描述甚少。为了为年轻患者的多靶点粪便 DNA（mt-sDNA）筛查提供生物学依据，我们分析并比较了 FDA 批准的 mt-sDNA 检测（Cologuard；Exact Sciences Corporation）中包含的甲基化（）和突变（）标志物的组织水平。
在 40-44、45-49 和 50-64 岁年龄组中，确定了 211 例散发性结直肠癌病例、123 例晚期癌前病变（腺瘤>1cm、高级别异型增生、≥25%绒毛状形态或无蒂锯齿状息肉；仅在 45-49 和 50-64 岁年龄组中）和 204 例组织学正常对照的存档结直肠组织标本。提取 DNA 后，使用 QuARTS 检测试剂盒定量检测、，并相对于（参考基因）进行定量。
除了 APL 样本中的浓度（与年轻病例相比，年龄较大的病例更高；=0.008）外，所有分子标志物的浓度均与年龄无显著相关性（所有比较>0.05）。然而，在 45-49（<0.0001）和 50-64（<0.0001）岁年龄组中，APL 病例与正常对照样本相比，水平也具有统计学意义上的升高。
总的来说，这些发现支持使用 mt-sDNA 检测对平均风险结直肠癌进行更早筛查。
这些新数据解决了一个已确定的知识空白，并为 mt-sDNA 检测对平均风险、早发筛查提供了更强的生物学依据。
