[Comparison of clinical and genetic phenotypes between Chinese and Korean hereditary nonpolyposis colorectal cancer families].
OBJECTIVE
To compare the clinical and genetic features between Chinese and Korean hereditary nonpolyposis colorectal cancer (HNPCC) families.


METHODS
Thirty-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.


RESULTS
In 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%.


CONCLUSIONS
(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.
Shen
Hong
H
Department of Oncology, 2nd Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang, 310009 People's Republic of China.
Yuan
Ying
Y
Song
Yong-mao
YM
Huang
Yan-qin
YQ
Zheng
Shu
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D044466:Asian People; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D013274:Stomach Neoplasms / Q000235:genetics; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein