Genetic architecture of colorectal cancer.
Genetic architecture of colorectal cancer.
复制标题
DOI：
10.1136/gutjnl-2013-306705
复制
发表时间：
2015-10
期刊：
影响因子：
24.5
通讯作者：
Zubair N
中科院分区：
文献类型：
--
作者：
Peters U;Bien S;Zubair N
结直肠癌（CRC）是一种复杂的疾病，是遗传和环境风险因素共同作用的结果。一小部分病例（3-5%）是由于十几个明确定义的基因突变而引起的遗传性综合征，易患早发性CRC。相反，CRC主要是一种迟发性“散发性”疾病，在没有明显遗传综合征的个体中发展。近年来，全基因组关联研究已经发现了40多个遗传区域与散发性CRC的弱效应相关，并且据估计，越来越大的全基因组扫描将识别出许多新的遗传区域。随后的实验验证已经在有限数量的这些遗传区域中鉴定了因果相关的变体。进一步的生物学洞察力可以通过种族多样性的研究人群，更大的基因测序研究，以及更高通量的功能实验的发展。沿着遗传变异，肿瘤基因组的整合可能揭示CRC的致癌过程。除了总结CRC的遗传结构，本文还讨论了改变CRC环境预测因子的遗传因素，以及遗传洞察力如何改善临床监测，预防和治疗策略的例子。总之，在揭示CRC的遗传结构方面已经取得了实质性进展，预计将继续开展研究工作，以确定其他遗传风险因素，进一步加深我们对这种疾病的生物学理解。
Colorectal cancer (CRC) is a complex disease that develops as a consequence of both genetic and environmental risk factors. A small proportion (3–5%) of cases arises from hereditary syndromes predisposing to early onset CRC as a result of mutations in over a dozen well-defined genes. In contrast, CRC is predominantly a late-onset “sporadic” disease, developing in individuals with no obvious hereditary syndrome. In recent years genome-wide association studies have discovered over 40 genetic regions to be associated with weak effects on sporadic CRC and it has been estimated that increasingly large genome-wide scans will identify many additional novel genetic regions. Subsequent experimental validations have identified the causally related variant(s) in a limited number of these genetic regions. Further biological insight could be obtained through ethnically diverse study populations, larger genetic sequencing studies, and development of higher-throughput functional experiments. Along with inherited variation, integration of the tumour genome may shed light on the carcinogenic processes in CRC. In addition to summarizing the genetic architecture of CRC, this review discusses genetic factors that modify environmental predictors of CRC, as well as examples of how genetic insight has improved clinical surveillance, prevention, and treatment strategies. In summary, substantial progress has been made in uncovering the genetic architecture of CRC and continued research efforts are expected to identify additional genetic risk factors that further our biological understanding of this disease.