MSH6 mutation carriers have later age of onset of both colorectal cancer (62 vs. 51 years) and endometrial cancer (58 vs. 48 years) and a larger proportion of endometrial cancer than MLH1 or MSH2 mutation carriers.
Later age of disease onset and lower incidence of colorectal cancer may contribute to a lower proportion of identified MSH6 mutations in families suspected of HNPCC.
When mutations in hMSH6 were included, more than 80% of Chinese colorectal cancer patients younger than 31 years had germline mutations in mismatch repair genes.
Our data suggest that germ-line msh6 mutations predispose individuals to primarily late-onset, familial colorectal carcinomas that do not fulfill classic criteria for HNPCC.