Arnold Christian N, Goel Ajay, Blum Hubert E, Boland C Richard
Department of Internal Medicine, University of Freiburg, Freiburg, Germany.
Cancer. 2005 Nov 15;104(10):2035-47. doi: 10.1002/cncr.21462.
Colorectal cancer is the third leading cause of cancer-related death in both men and woman in industrialized countries. Major advances have been made in our understanding of molecular events leading to formation of adenomatous polyps and cancer. Most colorectal cancers are sporadic, but a significant proportion (5-6%) has a clear genetic background. It is now widely accepted that colorectal carcinogenesis is a multistep process involving the inactivation of a variety of tumor-suppressor and DNA-repair genes and simultaneous activation of certain oncogenes. In addition, epigenetic alterations through aberrant promoter methylation and histone modification have been found to play a major role in the evolution and progression of a large proportion of sporadic colon cancers. Consequently, it is now apparent that individual colorectal cancers may evolve through diverse molecular pathways. In this article, the authors have summarized the current knowledge of molecular pathogenesis in common hereditary syndromes and sporadic forms of colorectal cancer. Novel molecular diagnostic tools for the early diagnosis and prevention of colorectal cancer that have emerged from these insights are discussed.
在工业化国家，结直肠癌是男性和女性癌症相关死亡的第三大主要原因。我们对导致腺瘤性息肉和癌症形成的分子事件的理解取得了重大进展。大多数结直肠癌是散发性的，但相当一部分（5%-6%）有明确的遗传背景。现在人们普遍认为，结直肠癌的发生是一个多步骤过程，涉及多种肿瘤抑制基因和DNA修复基因的失活以及某些癌基因的同时激活。此外，通过异常启动子甲基化和组蛋白修饰引起的表观遗传改变在很大一部分散发性结肠癌的发生和发展中起主要作用。因此，现在很明显，个体结直肠癌可能通过多种分子途径演变。在本文中，作者总结了常见遗传性综合征和散发性结直肠癌分子发病机制的当前知识。讨论了基于这些见解而出现的用于结直肠癌早期诊断和预防的新型分子诊断工具。
