Department of Internal Medicine, Division of Gastroenterology, Baylor Sammons Cancer Center, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas 75246, USA.
Curr Opin Gastroenterol. 2010 Jan;26(1):47-52. doi: 10.1097/MOG.0b013e328332b850.
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths in the Western world, but our understanding of this disease is incomplete. The recent advent of new technologies has provided novel insights into the pathogenesis of CRC.
Genome-wide association studies have recently linked CRC to 10 common genetic variants or single-nucleotide polymorphisms that map to chromosomes 8q23, 8q24, 10p14, 11q23, 14q22, 15q13, 16q22, 18q21, 19q13 and 20p1. However, the causal significance of these variants is not understood, and some are located in poorly characterized genomic regions or gene deserts. Recent studies indicate that the single-nucleotide polymorphism rs6983267, which maps to 8q24, serves as an enhancer of MYC expression by binding T cell factor 4 (TCF4) and influencing Wnt signaling. In addition, several microRNAs interact with genes such as K-RAS, APC, p53, PTEN, TCF4, COX-2, DNMT3a and DNMT3b. Germline hypermethylation of the DNA mismatch repair genes MLH1 and MSH2 may serve as predisposing events in some CRC patients.
Recent studies have elucidated novel mechanisms involved in CRC, including the involvement of single-nucleotide polymorphisms not located within traditional genes, the role of microRNAs and epimutations in DNA mismatch repair genes. Interestingly, most of this progress has been made by understanding DNA that does not encode genes.
结直肠癌（CRC）是西方世界癌症相关死亡的主要原因之一，但我们对这种疾病的认识并不完整。最近新技术的出现为 CRC 的发病机制提供了新的见解。
全基因组关联研究最近将 CRC 与 10 个常见的遗传变异或单核苷酸多态性联系起来，这些变异或单核苷酸多态性映射到染色体 8q23、8q24、10p14、11q23、14q22、15q13、16q22、18q21、19q13 和 20p1。然而，这些变体的因果意义尚不清楚，有些位于特征较差的基因组区域或基因沙漠中。最近的研究表明，单核苷酸多态性 rs6983267 映射到 8q24，通过与 T 细胞因子 4（TCF4）结合并影响 Wnt 信号，作为 MYC 表达的增强子。此外，几种 microRNAs 与 K-RAS、APC、p53、PTEN、TCF4、COX-2、DNMT3a 和 DNMT3b 等基因相互作用。DNA 错配修复基因 MLH1 和 MSH2 的胚系超甲基化可能是某些 CRC 患者的易患事件。
最近的研究阐明了 CRC 涉及的新机制，包括涉及不在传统基因内的单核苷酸多态性，microRNAs 和 DNA 错配修复基因中的表观遗传变化的作用。有趣的是，这项进展主要是通过了解不编码基因的 DNA 来实现的。
