Genetic diagnosis and management of suspected hereditary nonpolyposis colorectal cancer

The status of the hMLH1 and hMSH2 genes was investigated in suspected hereditary nonpolyposis colorectal cancer (HNPCC) patients who do not fulfill the ICG-HNPCC criteria, but in whom a genetic basis of colon cancer is strongly suspected. Two different sets of criteria (criteria I and II) were designed to select the patients for genetic testing. Peripheral blood samples were collected and genomic DNA isolated from 31 families fulfilling criteria I and 45 early-onset colorectal cancer patients in whom colorectal cancer was diagnosed before the age of 40 (a subgroup of criteria II). All coding regions of the hMLH1 and hMSH2 genes were screened by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP), followed by DNA sequencing of the DNA fragments displaying an abnormal SSCP pattern. Seven germline mutations (23%) were identified in the patients fulfilling criteria I, and one (2%) in the early-onset colorectal cancer patients. In view of the 31% mutation detection rate in the 29 ICG-HNPCC families at the Korean Hereditary Tumor registry, our data suggest that criteria I for suspected HNPCC are useful in selection of patients and their family members who would benefit from genetic diagnosis. Results of DNA testing would have a great impact on the management of suspected HNPCC patients and their family members.