Baba S
Hamamatsu University School of Medicine, Japan.
Gan To Kagaku Ryoho. 1999 May;26(6):735-43.
Familial cancers associated with genetic background are of the most intensively investigated diseases in recent years. The phenotype is apparent with most of these diseases and can easily be traced through family history. Induction in familial cancer appears, on current evidence, to be not different from that observed in sporadic cancer. The first suppressor gene Rb gene was cloned from retinoblastoma. There are two representative hereditary colorectal cancers: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC). The gene responsible for FAP (APC gene) was cloned in 1991. The APC gene is a negative regulator of beta-catenin and is considered to play the role of gatekeeper in the adenoma carcinoma sequence. Thereafter a group of genes, human homologues of mismatch repair genes (hMSH2, hMLH1, hPMS1, hPMS2, hMSH6), have been identified as the genes responsible for HNPCC. These are called care taker genes, which serve to maintain genetic stability. Therefore, if one of those genes undergoes mutation, the rate of mutation increases significantly. It has only been in the last 20 years that familial cancer has become an important issue. In association with such advances, predictive testing can now be performed on at risk persons. Persons at risk can thus be accurately counseled and screened for early detection of disease.
与遗传背景相关的家族性癌症是近年来研究最为深入的疾病之一。这些疾病中的大多数都具有明显的表型，并且可以通过家族病史轻松追溯。根据目前的证据，家族性癌症的诱发似乎与散发性癌症中观察到的情况并无不同。第一个抑癌基因Rb基因是从视网膜母细胞瘤中克隆出来的。有两种典型的遗传性结直肠癌：家族性腺瘤性息肉病（FAP）和遗传性非息肉病性结直肠癌（HNPCC）。导致FAP的基因（APC基因）于1991年被克隆。APC基因是β-连环蛋白的负调节因子，被认为在腺瘤癌序列中起守门人的作用。此后，一组基因，即错配修复基因的人类同源物（hMSH2、hMLH1、hPMS1、hPMS2、hMSH6），已被确定为导致HNPCC的基因。这些被称为守护者基因，其作用是维持遗传稳定性。因此，如果这些基因中的一个发生突变，突变率会显著增加。直到最近20年，家族性癌症才成为一个重要问题。随着这些进展，现在可以对高危人群进行预测性检测。因此，可以为高危人群提供准确的咨询和筛查，以便早期发现疾病。
