hMLH1和hMSH2种系突变携带者累积患癌风险研究

目的：探讨遗传性非息肉病性结直肠癌（HNPCC）家系中错配修复基因hMLH1和hMSH2种系突变携带者发生HNPCC相关恶性肿瘤的累积风险度。方法：通过随访14个HNPCC家系中222例hMLH1或hMSH2种系突变携带者与非携带者,应用SPSS14.0统计软件包分析种系突变携带者在不同年龄点发生HNPCC相关恶性肿瘤的累积风险度及两种基因种系突变累积患癌风险的差异。结果：hMLH1或hMSH2种系突变携带者肿瘤发生率为63.8%（60/94）,非突变携带者肿瘤发生率为0.8%（1/128）,种系突变携带者发生恶性肿瘤的相对危险度为非突变携带者的317.6倍;种系突变携带者发生各种HNPCC相关恶性肿瘤的累积风险度随年龄的增加逐渐增大,在60岁时发生各种HNPCC相关恶性肿瘤、结直肠癌、胃癌等的平均累积风险度分别为92.4%、81.3%、29.6%,40岁以前发生胃癌的平均风险度较低（6.1%）;hMLH1与hMSH2种系突变携带者发生各种HNPCC相关恶性肿瘤、结直肠癌、胃癌等累积风险度的差异无统计学意义（均为P＆gt;0.05）。结论：hMLH1或hMSH2种系突变携带者为HNPCC家系中患癌高危人群，发生HNPCC相关恶性肿瘤的风险度随年龄的增加而增大，最常发生恶性肿瘤的部位为胃和结直肠；hMLH1与hMSH2种系突变携带者发生各种HNPCC相关恶性肿瘤的累积风险度无明显差异。

Cumulative Cancer Risk of hMLH1and hMSH2 Germline Mutation Carriers in HNPCC Families

Objective： Hereditary nonpolyposis colorectal cancer （HNPCC） is linked to germline mutations in mismatch repair genes （MMR）. This study is to investigate the cumulative cancer risk of hMLHland hMSH2 germline mutation carriers in HNPCC fami- lies in China. Methods： 222 members were previously received detection of the mutation status of hMLHland hMSH2 in 14 HNPCC families. Among them, there were 94 individuals proven or assumed hMLH1 or hMSH2 mutations. The Kaplan-Meier analysis of Cumu- lative cancer risk to mutation carriers of 30, 40, 50 and 60 years were calculated by SPSS14.0. The difference of cumulative cancer risk between hMLHland hMSH2 mutation carriers was also analyzed. Results： Cancer incidence is 63.8% （60/94）in 94 hMLH1 or hMSH2 mutation carriers. Compared with non-mutation carriers, the relative risk to mutation carriers is 317.6. Cumulative cancer risk increases with the age of mutation carriers. At 60 years old, the carrier is respectively of 92.4%, 81.3% and 29.6% of cumulative risk to any malig- nant tumor, colorectal cancer and gastric; while before 40 years old, the cumulative risk of gastric cancer is very low （6.1%）. the differ- ence of cumulative risk to any malignant cancer, colorectal cancer and gastric cancer between the hMLHland hMSH2 mutation carriers has no statistical significance （all P〉0.05）. Conclusions： hMLHland hMSH2 germline mutation carriers are high risk population to de- velop caners. The cumulative risk to develop HNPCC spectrum malignancies increases along with the age of mutation carriers. There is no obvious diffemece of cumulative cancer risk between hMLH 1 and hMSH2 mutation carriers.