Molecular pathogenesis of colorectal cancer

Abstract

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. Cancer 2005. © 2005 American Cancer Society.