Effects of genetic polymorphisms of MDR1, FMO3 and CYP1A2 on susceptibility to colorectal cancer in Koreans

The aim of the present study was to evaluate the effects on the susceptibility to colorectal cancer (CRC) of genetic polymorphisms in P-glycoprotein (PGP) and the metabolic enzymes cytochrome P450 1A2 (CYP1A2) and flavin-containing monooxygenase 3 (FMO3). We analyzed five single-nucleotide polymorphisms (SNP) in 93 cancer-free volunteers and 111 patients with CRC: one common genetic variant of the PGP-encoding MDR1 gene and four SNP in genes for metabolic enzymes (two SNP in FMO3 and two SNP in CYP1A2). The genotypes and allele frequencies of the MDR1/C3435T, FMO3/G488A, FMO3/A923G and CYP1A2/G-3860 A polymorphisms were not significantly different in cancer-free subjects and CRC patients. However, a significant association was found between the CYP1A2/A-163C polymorphism and the risk of CRC, particularly in elderly (> 55 years) subjects and smokers. A phenotyping study in normal smokers showed that the CYP1A2 activity of subjects with the CYP1A2/-163 AA genotype was significantly lower than that of subjects carrying the CYP1A2/-163C allele. Combined results show that the CYP1A2/-163C allele is significantly associated with an increase in CYP1A2 activity and a consequent increased risk of CRC in Koreans, particularly in elderly people and smokers.