Cremin Carol M, Armstrong Linlea, Gill Sharlene, Huntsman David, Bajdik Chris
Hereditary Cancer Program, BC Cancer Agency, Vancouver, Canada.
Can J Gastroenterol. 2009 Nov;23(11):761-7. doi: 10.1155/2009/620518.
To determine the prevalence of Lynch syndrome mutations in a Canadian hereditary cancer clinic population, and to determine the effectiveness of the program's referral criteria and testing algorithm.
A retrospective chart review of all patients who were referred for and received genetic counselling at the BC Cancer Agency's Hereditary Cancer Program for a family history of colon cancer from August 1, 2004, to September 1, 2006, was performed. Charts were reviewed for referral criteria met, cancer history, whether testing was offered and the outcome of testing.
Lynch syndrome was confirmed or highly suspected in 14.3% of index test patients (eight of 56) by the identification of a deleterious mutation or variant likely to be deleterious in either of the hMLH1 or hMSH2 mismatch repair genes. In the program, the two most effective criteria were a personal diagnosis of two or more primary Lynch syndrome-related cancers (one diagnosed at younger than 50 years of age) or two first-degree relatives with a Lynch syndrome-related cancer (both diagnosed at younger than 50 years of age). The respective positive predictive values of these two criteria were calculated to be 66.7% (95% CI 40% to 93%) and 58.3% (95% CI 30.4% to 86.2%).
The Hereditary Cancer Program developed and successfully implemented an approach that selected individuals at risk for Lynch syndrome with a significant pretest probability of mutation of 14.3%. Improved ascertainment of families with Lynch syndrome will require greater physician awareness of referral criteria, program advances in the testing algorithm and a population-based approach to screening incident colon cancers.
确定加拿大遗传性癌症门诊患者中林奇综合征突变的患病率，并确定该项目转诊标准和检测算法的有效性。
对2004年8月1日至2006年9月1日期间因结肠癌家族史被转介至不列颠哥伦比亚癌症机构遗传性癌症项目并接受遗传咨询的所有患者进行回顾性病历审查。审查病历以确定是否符合转诊标准、癌症病史、是否提供检测以及检测结果。
通过鉴定hMLH1或hMSH2错配修复基因中可能有害的有害突变或变异，在14.3%的索引检测患者（56例中的8例）中确诊或高度怀疑林奇综合征。在该项目中，两个最有效的标准是个人诊断患有两种或更多原发性林奇综合征相关癌症（其中一种在50岁之前诊断）或两名一级亲属患有林奇综合征相关癌症（均在50岁之前诊断）。这两个标准各自的阳性预测值经计算分别为66.7%（95%CI 40%至93%）和58.3%（95%CI 30.4%至86.2%）。
遗传性癌症项目制定并成功实施了一种方法，该方法筛选出有林奇综合征风险且突变前检测概率高达14.3%的个体。要更好地确定林奇综合征家族，需要医生提高对转诊标准的认识、检测算法方面的项目进展以及基于人群的方法来筛查偶发性结肠癌。
