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Abstract：
Colorectal cancer (CRC) is a complex disease that can be caused by a spectrum of genetic variants ranging from low to high penetrance changes, that interact with the environment to determine which individuals will develop the disease. In this study, we sequenced 20 early-onset CRC patients to discover novel genetic variants that could be linked to the prompt disease development. Eight genes, CHAD, CHD1L, ERCC6, IGTB7, PTPN13, SPATA20, TDG and TGS1, were selected and re-sequenced in a further 304 early onset CRC patients to search for rare, high-impact variants. Although we found a recurring truncating variant in the TDG gene shared by two independent patients, the results obtained did not help consolidate any of the candidates as promising CRC predisposing genes. However, we found that potential risk alleles in our extended list of candidate variants have a tendency to appear at higher numbers in younger cases. This supports the idea that CRC onset may be oligogenic in nature and may show molecular heterogeneity. Further, larger and robust studies are thus needed to unravel the genetics behind early-onset CRC development, coupled with novel functional analyses and omic approaches that may offer complementary insight.
摘要：
结直肠癌（CRC）是一种复杂的疾病，可能是由一系列从低到高外显率变化的遗传变异引起的，与环境相互作用以确定哪些人会患上这种疾病。在这项研究中,我们对20例早发型CRC患者进行了测序,以发现可能与疾病迅速发展相关的新的遗传变异.八个基因,CHAD,CHD1L,选择ERCC6，IGTB7，PTPN13，SPATA20，TDG和TGS1，并在另外304例早发性CRC患者中进行重新测序，以寻找罕见的，高影响力的变体。尽管我们在TDG基因中发现了由两名独立患者共享的重复截断变体，获得的结果无助于巩固任何候选基因作为有前景的CRC易感基因.然而,我们发现,我们扩展的候选变异列表中的潜在风险等位基因在年轻病例中倾向于出现更高的数量.这支持CRC发病本质上可能是寡基因的并且可能显示分子异质性的想法。Further,因此，需要更大规模和强有力的研究来解开早发性CRC发展背后的遗传学，再加上新的功能分析和组学方法，可以提供互补的见解。
