Lynch H T, Lynch J F
Department of Preventive Medicine, Creighton University School of Medicine, Omaha, Nebraska 68179, USA.
Tumori. 1995 May-Jun;81(3 Suppl):19-29.
Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common occurring hereditary form of colorectal cancer (CRC) where it accounts for as much as 10 percent of the total CRC burden. HNPCC is characterized by an autosomal dominant inherited predisposition to early age of onset (= 44 years) of CRC with proximal predominance (= 70% proximal to the splenic flecture) with an excess of synchronous and metachronous CRC (45% 10 years after initial hemicolectomy or segmental resection as opposed to subtotal colectomy), features which characterize the Lynch syndrome I variant, while the Lynch syndrome II variant of HNPCC shows all of these features, but in addition, there is a marked excess of carcinoma of the endometrium, ovary, small bowel, stomach, pancreas, and transitional cell carcinoma of the ureter and renal pelvis, lesions which are integral to this syndrome. Because of the early onset, we recommend colonoscopy to be initiated at age 25 and repeated every other year through age 35 and then annually thereafter. Women need to undergo endometrial aspiration biopsy at the time of initial colonoscopy.
Major advances in the molecular genetics of HNPCC have occurred during the past two years with identification of the hMSH2 gene at chromosome 2p and the hMLH1 gene at chromosome 3p, both of which have been cloned. PMS1 at chromosome 2p and PMS2 2 at chromosome 7q have also been implicated in HNPCC's etiology.
Genetic counseling is mandatory for presymptomatic DNA testing and for delivering information about the patient's germline status. Patients with germline mutations are offered prophylactic subtotal colectomy as an option to continued colonoscopy. It is now important for physicians to take careful cancer family histories so that this disorder can be readily identified, thereby enabling the initiation of highly targeted surveillance and management programs.
遗传性非息肉病性结直肠癌（HNPCC）是结直肠癌（CRC）最常见的遗传性类型，占CRC总负担的10%。HNPCC的特征是常染色体显性遗传易患早发性（≤44岁）CRC，近端优势（脾曲近端占70%），同步和异时性CRC发生率高（初始半结肠切除术或节段性切除术后10年为45%，而次全结肠切除术则不然），这些特征是林奇综合征I型变异的特点，而HNPCC的林奇综合征II型变异具有所有这些特征，但此外，子宫内膜癌、卵巢癌、小肠癌、胃癌、胰腺癌以及输尿管和肾盂移行细胞癌的发生率显著增加，这些病变是该综合征的组成部分。由于发病早，我们建议在25岁开始结肠镜检查，35岁前每隔一年重复检查一次，此后每年检查一次。女性在首次结肠镜检查时需要进行子宫内膜抽吸活检。
在过去两年中，HNPCC分子遗传学取得了重大进展，已鉴定出位于2号染色体p臂的hMSH2基因和位于3号染色体p臂的hMLH1基因，二者均已被克隆。位于2号染色体p臂的PMS1和位于7号染色体q臂的PMS2也与HNPCC的病因有关。
对于症状前DNA检测和提供患者种系状态信息，遗传咨询是必需的。对于种系突变患者，可选择预防性次全结肠切除术以替代持续的结肠镜检查。现在医生仔细记录癌症家族史很重要，以便能容易地识别这种疾病，从而启动高度针对性的监测和管理方案。
