Meta-analysis of MSH6 gene mutation frequency in colorectal and endometrial cancers.
Studies on mutations and mutation frequencies of the MSH6 gene, which mainly focus on new types of mutations in small samples, have been published ever since the first report of MSH6 mutation in two atypical hereditary non-polyposis colorectal cancer patients. However, the results remain inconsistent. Therefore, a systematic review was conducted and a meta-analysis was undertaken to determine the frequency of MSH6 mutation in colorectal and endometrial cancers. From 27 studies, 180 cases with MSH6 mutation in a total of 3196 cases were detected. In colorectal and endometrial cancers the MSH6 mutation frequency is 7.2 and 9.6%, respectively. MSH6 mutation frequency was 10.4% in hereditary non-polyposis colorectal cancer patients, 7.1% in atypical hereditary non-polyposis colorectal cancer patients, and 5.9% in sporadic patients. The frequency of MSH6 mutation in high microsatellite instability (MSI-H) was 11.6% and in low microsatellite instability (MSI-L) cases was (13.3%), which were higher than in microsatellite stability (MSS) cases (1.7%). The mean age of the earliest onset of colorectal and endometrial cancers in MSH6 mutation carriers was 51.2 and 56.5 yr, respectively. Data suggest that the frequency of MSH6 mutation is higher in hereditary non-polyposis colorectal cancer patients than in atypical hereditary non-polyposis colorectal cancer and sporadic patients. MSH6 mutation frequency was also higher in endometrial than colorectal cancers. The mean age of earliest onset of endometrial cancer (56.5 yr) is older than for colorectal cancer (51.2 yr) in carriers of MSH6 mutation. Our results provide evidence for clinical genetic testing and counseling.
Zhao
Ya-shuang
YS
Department of Epidemiology, Public Health College, Harbin Medical University, Heilongjiang Province, People's Republic of China. zhao_yashuang@263.net
Hu
Fu-lan
FL
Wang
Fan
F
Han
Bing
B
Li
Dan-dan
DD
Li
Xiang-wei
XW
Zhu
Sui
S
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein