Glutathione S-Transferase, N-Acetyltransferase,Cytochrome P450 Polymorphisms in Patients with Basal Cell Carcinoma

Abstract

Background: GST, NAT and CYP polymorphisms have been shown to influence the level of oxidative DNA damage. Also, there is a consensus that ROS play part in the epidermal carcinogenesis. Aim: Our purpose was to investigate the GST, NAT and CYP polymorphism in patients with skin cancer. Material and Methods: Ninety seven subjects, 34 women and 63 men, with basal cell carcinoma, and 117 healthy control subjects, 52 women and 65 men, were enrolled in the study. The polymorphisms of GSTT1, GSTM1, GSTP, NAT2*5A, NAT2*6A, NAT2*7A/B, NAT2*14A, CYPC9*2, CYP2C9*3 CYPC19*2, CYP2C19*3 were performed by real time PCR. Results: Patients (51.5%) had a higher prevalence of the GSTM1 null genotype than the control group (33.3%) and we found a 2.12 fold increased risk of skin cancer in individuals with the GSTM1 null genotype when compared to the control group. In the patient group, the frequency of the NAT2*6A heterozygous genotype was higher in comparison with that of the control group and this increase was statistically significant (p=0,004 OR=3,70; 95% CI: 1,53-8,95). Patients with the NAT2*7A/B heterozygous genotype had a higher risk of skin cancer compared with individuals with the NAT2*7A/B wild genotype (p=0,001 OR = 0,17; 95% CI = 0,06-0,048). CYP2C9*3 heterezygous genotype was higher in patient group (p=0.015 OR=2.02; 95% CI: 1.14-3.57). Compared with the CYP2C19*2 wild genotype, CYP2C19*2 heterezygous genotype was associated with more than 2.8 fold increased risk of skin cancer (p= 0.001, 95% CI: 1.50-5.26). These varying enzyme activities are supposed to influence the individual metabolism of carcinogenic aromatic amines, thereby modifying the susceptibility to certain cancers. Conclusion: In our study, the results from the patient group suggest that there may be a relation between GST, NAT and CYP gene polymorphisms and basal cell carcinoma.