OBJECTIVETo compare the clinical and genetic features between Chinese and Korean hereditary nonpolyposis colorectal cancer (HNPCC) families.

METHODSThirty-one Chinese HNPCC families and 63 HNPCC Korean families were involved in this study. The clinical data of the probands and families were collected. Genomic DNAs were prepared from peripheral blood samples of probands for DNA test. PCR and DHPLC were employed to screen the mutations. Sequencing analysis was followed to find out the exact mutation site and feature in samples showing abnormalities in SSCP or DHPLC analysis.

RESULTSIn a total, there were 136 malignant neoplasms diagnosed in the 31 Chinese families, about 77.9% of them were colorectal cancer. The mean age of colorectal cancer at diagnosis was (48.6+/- 29.0) years. Gastric cancer was the second most common cancer in these familiesîSeven pathogenic mutations (3 in hMLH1 gene and 4 in hMSH2 gene) were detected in the 31 probands, including 2 missense mutations, 2 nonsense mutations, 2 frameshift mutations and 1 large-fragment deletion. The total mutation rate was 22.6%. In the 63 Korean families, 293 malignant neoplasms were documented, 82.6% of them were diagnosed as colorectal cancer. The mean age of colorectal cancer at diagnosis was (45.9+/- 11.0) years. Gastric cancer was also the most common extracolonic cancer in these Korean families. Nineteen pathogenic mutations (17 in hMLH1 gene and 2 in hMSH2 genes) were detected in the 63 probands, including 12 frameshift mutations, 5 missense mutations, 1 nonsense mutation and 1 base-change at the splicing site. The total mutation rate was 30.2%.

CONCLUSION(1) Chinese and Korean HNPCC families had many similar clinical features, such as early-onset of colorectal cancer, predominance in distal colon and rectum, lower incidence of synchronous or metachronous colorectal cancers as compared with Western countries, and a frequent occurrence of gastric cancer in the families. (2) The total mutation rate of hMLH1 and hMSH2 gene in Chinese and Korean HNPCC families was similar and lower than that reported in Western countries. But the mutation characteristics, such as predominant gene, mutation type and mutation distribution, were different in the two populations.