RELATION BETWEEN THE OCCURRENCE OF K-RAS GENE POINT MUTATIONS AND GENOTYPES OF POLYMORPHIC N-ACETYLTRANSFERASE IN HUMAN COLORECTAL CARCINOMAS

We examined the point mutations of codons 12, 13 and 61 in K-ras gene by slot blot hybridization analysis following polymerase chain reaction and genotypes of polymorphic N-acetyltransferase (NAT) by Southern blot analysis in 36 colorectal carcinoma tissues obtained at surgery. NAT genotypes of 36 autopsied livers from patients without colorectal carcinoma were also determined to compare the populations of each polymorphic NAT genotype in the patients with or without the neoplasm. Genetically, 44.4% (16 cases), 47.2% (17 cases) and 8.3% (3 cases) of patients with colorectal carcinoma were classified as rapid, intermediate and slow acetylators, respectively. Point mutations of K-ras gene were detected in eight carcinomas out of 16 rapid acetylators, two out of 17 intermediate acetylators and one out of three slow acetylators. In control livers, 52.8% (19 cases), 38.9% (14 cases) and 8.3% (3 cases) were classified as rapid, intermediate and slow acetylators, respectively. The occurrence of K-ras gene point mutations was closely linked to rapid acetylator genotype, although there was no statistical difference of NAT genotypes between the group of patients with colorectal carcinoma and the group of controls.