부산대학교 도서관

BACKGROUND: The incidence of colorectal cancer in persons under 46 years of age issubstantially higher in Hong Kong than in Scotland and many other countries. Consequently, weexamined whether there is a hereditary predisposition for colorectal cancer in this SouthernChinese population. METHODS: We investigated the incidence of microsatellite instability(MSI) at 10 DNA sites in 117 colorectal cancer specimens from Chinese patients of various ages.Those tumors with new alleles at 40% or more of the sites investigated were identified ashighly unstable MSI (MSI-H). In young patients, we also searched for germline mutations inthree mismatch repair genes (hMSH2, hMLH1, and hMSH6). RESULTS: The incidence ofMSI-H varied statistically significantly with age, being observed in more than 60% ofthose younger than age 31 years at diagnosis and in fewer than 15% of those age 46 yearsor older. In 15 patients (<46 years old) whose colorectal cancers showed MSI-H, eightpossessed germline mutations in either hMSH2 or hMLH1. When mutations in hMSH6 wereincluded, more than 80% of Chinese colorectal cancer patients younger than 31 years hadgermline mutations in mismatch repair genes. We found a novel germline missense mutation inhMSH6 in a 29-year-old man whose tumor showed no MSI. Two patients had a 4-base-pairinsertion in exon 10 causing a truncated protein; this insertion is a common polymorphism with apopulation allele frequency in Chinese of 5.6%. CONCLUSIONS: Our results indicatethat germline mutations in mismatch repair genes contribute substantially to the pathogenesis andhigh incidence of colorectal cancer in young Hong Kong Chinese. However, because youngChinese and Caucasians show similar proportions of colorectal cancers with MSI-H, despite thehigher incidence in the former, additional factors may underlie the high susceptibility of youngChinese to colorectal cancer.