Colorectal cancer affected approximately 135,000 people in the United States in 2001, resulting in 57,000 deaths. Colorectal cancer develops as the result of the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic epithelium to colon adenocarcinoma. The loss of genomic stability is a key molecular and pathophysiologic step in this process and serves to create a permissive environment for the occurrence of alterations in tumor suppressor genes and oncogenes. Alterations in these genes, which include APC, CTNNB1, K-RAS, MADH4/SMAD4, and TGFBR2, appear to promote colon tumorigenesis by perturbing the function of signaling pathways, such as the TGF-ss signaling pathway, or by affecting genes that regulate genomic stability, such as the mutation mismatch repair genes.

中文翻译：

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结肠癌的遗传和表观遗传学改变。

大肠癌在2001年影响了美国大约13.5万人，导致57,000例死亡。大肠癌的发展是遗传和表观遗传学改变逐渐累积的结果，这些遗传和表观遗传学改变导致正常结肠上皮向结肠腺癌转化。基因组稳定性的丧失是该过程中的关键分子和病理生理学步骤，并为肿瘤抑制基因和癌基因的发生变化创造了宽松的环境。这些基因的改变，包括APC，CTNNB1，K-RAS，MADH4 / SMAD4和TGFBR2，似乎通过干扰信号传导途径（例如TGF-ss信号传导途径）的功能或通过影响调控基因来促进结肠肿瘤发生。基因组稳定性，例如突变错配修复基因。