Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
Geriatr Gerontol Int. 2010 Jul;10 Suppl 1:S207-12. doi: 10.1111/j.1447-0594.2010.00590.x.
The occurrence of malignant neoplasms increases with advancing age. Although aging and carcinogenesis are basically different processes, they share phenomena such as the accumulation of DNA damage and abnormal proteins. Recent advances in molecular biology have shown an accumulation of genetic and epigenetic changes in both aging and carcinogenesis, as well as the alteration of metabolism, immunosenescence and shortened telomeres. DNA methylation is a representative epigenetic phenomenon and is frequently involved in controlling gene functions during development and tumorigenesis. We herein focused on methylation of genes in the development of gastrointestinal carcinomas in the elderly. The proportion of gastric and colorectal carcinomas with hypermethylation of the hMLH1 promoter increases with age, reaching 25-30% of all carcinomas of the stomach and large intestine in elderly patients. These tumors have clinicopathological and molecular characteristics such as loss of hMLH1 expression, microsatellite instability, poorly differentiated histology, peritumoral inflammatory cell infiltration, low incidence of lymph node metastasis and favorable prognosis. However, methylation-related carcinogenesis accounts for up to approximately one-third of tumors, and other mechanisms; for example chromosomal instability as a result of telomere dysfunction, are responsible for the development of most carcinomas in the elderly.
恶性肿瘤的发生随着年龄的增长而增加。虽然衰老和癌变是基本不同的过程，但它们共享 DNA 损伤和异常蛋白质积累等现象。分子生物学的最新进展表明，衰老和癌变过程中都存在遗传和表观遗传变化的积累，以及代谢、免疫衰老和端粒缩短的改变。DNA 甲基化是一种代表性的表观遗传现象，经常参与控制发育和肿瘤发生过程中的基因功能。本文重点介绍了老年人胃肠道癌发生过程中基因的甲基化。hMLH1 启动子高甲基化的胃癌和结直肠癌的比例随着年龄的增长而增加，在老年患者的胃和大肠所有癌中达到 25-30%。这些肿瘤具有临床病理和分子特征，如 hMLH1 表达缺失、微卫星不稳定、组织学分化差、肿瘤周围炎症细胞浸润、淋巴结转移发生率低和预后良好。然而，与甲基化相关的致癌作用占肿瘤的比例高达约三分之一，而其他机制，如端粒功能障碍导致的染色体不稳定性，是导致老年人大多数癌症发展的原因。
