Lynch H T, Smyrk T, Lynch J
Creighton University School of Medicine, Department of Preventive Medicine, Omaha, Nebraska 68178, USA.
Cancer Genet Cytogenet. 1997 Jan;93(1):84-99. doi: 10.1016/s0165-4608(96)00290-7.
Genetic epidemiology studies of colorectal cancer (CRC) can identify persons who are at inordinately high risk and who thereby might benefit from targeted early detection and primary prevention programs, inclusive of prophylactic surgery in selected cases. The discipline of molecular genetics has identified germline mutations that include APC in familial adenomatous polyposis (FAP) and mutator genes, namely MSH2, MLH1, PMS1, and PMS2 in hereditary nonpolyposis colorectal cancer (HNPCC). These discoveries have significantly enhanced our ability to identify individuals whose cancer destiny can literally be determined at birth. This review updates HNPCC's differential diagnosis, heterogeneity, tumor spectrum, newly found evidence of accelerated colonic adenoma to CRC, survival advantage, and currently available surveillance and management programs. Emphasis has been on how knowledge of the genetics and natural history of HNPCC can be used effectively to promote early diagnosis or prevention of cancer.
结直肠癌（CRC）的遗传流行病学研究能够识别出患癌风险极高的人群，这些人可能会从有针对性的早期检测和一级预防项目中受益，包括在某些情况下进行预防性手术。分子遗传学学科已经鉴定出一些种系突变，包括家族性腺瘤性息肉病（FAP）中的APC基因，以及遗传性非息肉病性结直肠癌（HNPCC）中的错配修复基因，即MSH2、MLH1、PMS1和PMS2。这些发现显著提高了我们识别那些在出生时其癌症命运就已基本确定的个体的能力。这篇综述更新了HNPCC的鉴别诊断、异质性、肿瘤谱、新发现的结肠腺瘤向CRC加速发展的证据、生存优势以及目前可用的监测和管理方案。重点在于如何有效地利用HNPCC的遗传学和自然史知识来促进癌症的早期诊断或预防。
