NAT2 fast acetylator genotype and MGMT promoter methylation may contribute to gender difference in K-RAS mutation occurrence in Taiwanese colorectal cancer

A recent study conducted by our group showed that the NAT2 fast acetylator genotype is associated with an increasing risk for the development of colorectal cancer (CRC), especially for females. We therefore examined whether a higher risk of CRC in females with the NAT2 fast acetylator genotype was associated with the occurrence of K-RAS mutation, and to further verify whether MGMT promoter methylation was linked to the occurrence of K-RAS mutation in patients with the NAT2 fast acetylator genotype. Herein, 151 CRC cases were examined for NAT2 genetic polymorphisms and MGMT promoter methylation by PCR-RFLP and methylation-specific PCR (MSP). The results of this study show that the NAT2 fast acetylator genotype is associated with the occurrence of K-RAS mutation in female cases (OR = 4.820, 95% CI = 1.113–20.873), but not associated with MGMT promoter methylation. Surprisingly, MGMT promoter methylation significantly deepens the impact of NAT2 fast acetylation on K-RAS mutation in the female cases (OR = 5.129, 95% CI = 1.092–24.105). In conclusion, Taiwanese women with the NAT2 fast acetylator genotype may exhibit a higher risk of CRC with increased occurrence of K-RAS mutation. Detection of NAT2 genotypes and MGMT promoter methylation may be useful in the risk assessment for CRC in Taiwanese women. Environ. Mol. Mutagen., 2009. © 2008 Wiley-Liss, Inc.