Bishop D T, Thomas H J
Imperial Cancer Research Fund Genetic Epidemiology Laboratory, Leeds, UK.
Cancer Surv. 1990;9(4):585-604.
Two features of colorectal cancer have greatly aided the recent progress in understanding its genetics: firstly the majority of colorectal cancers arise from premalignant adenomatous polyps allowing the analysis of somatic genetic changes during tumorigenesis, and secondly there are several well defined inherited syndromes that predispose to colorectal cancer in an autosomal dominant manner. The familial polyposis gene has been mapped to chromosome 5q and loss of material on chromosome 5 shown in a large proportion of sporadic (non-familial) adenomas and carcinomas. Allele loss has also been found in a high proportion of colorectal cancers on chromosomes 17 and 18 and the respective genes involved identified as that coding for the oncoprotein p53 on 17p and the DCC ('deleted in colorectal carcinomas') gene on 18q. In addition activation of k-ras is found frequently in colorectal adenomas and carcinomas. The development of colorectal neoplasia is associated with the accumulation of genetic changes. Family studies of apparently sporadic colorectal cancer probands have shown an increased incidence of adenomas and carcinomas in first degree relatives. More recently pedigree studies have suggested that an inherited predisposition may be responsible for the majority of colorectal tumours.
其一，大多数结直肠癌起源于癌前腺瘤性息肉，这使得在肿瘤发生过程中对体细胞遗传变化进行分析成为可能；其二，存在几种明确的遗传性综合征，它们以常染色体显性方式使个体易患结直肠癌。家族性息肉病基因已被定位到5号染色体长臂，并且在大部分散发性（非家族性）腺瘤和癌中都显示出5号染色体上物质的缺失。在17号和18号染色体上，也在高比例的结直肠癌中发现了等位基因缺失，并且所涉及的相关基因已被确定为17号染色体短臂上编码癌蛋白p53的基因以及18号染色体长臂上的DCC（“结直肠癌缺失”）基因。此外，在结直肠腺瘤和癌中经常发现k-ras的激活。结直肠肿瘤的发生与遗传变化的积累相关。对明显为散发性结直肠癌先证者的家族研究表明，一级亲属中腺瘤和癌的发病率有所增加。最近的系谱研究表明，遗传易感性可能是大多数结直肠肿瘤的病因。
