Purpose: We examined the influence of XPC A2920C, XPF T30028C, TP53 Arg72Pro and GSTP1 Ile105Val polymorphisms in the risk of cutaneous melanoma (CM).
Methods: DNA from 146 CM patients and 146 controls was analysed by polymerase chain reaction (PCR)--restriction fragment length polymorphism (RFLP).
Results: The frequencies of XPC CC (15.1 vs. 6.9 %, P = 0.02), TP53 ArgArg (59.6 vs. 45.9 %, P = 0.02), XPC CC plus TP53 ArgArg (19.7 vs. 5.2 %, P = 0.01) and TP53 ArgArg plus GSTP1 IleIle (50.7 vs. 35.6 %, P = 0.03) genotypes were higher in patients than in controls. Carriers of the respective genotypes were under a 2.51 (95 % CI: 1.13-5.55), 1.76 (95 % CI: 1.09-2.83), 4.52 (95 % CI: 1.35-15.16), and 2.01 (95 % CI: 1.04-3.90)-fold increased risks for CM than others, respectively. An excess of TP53 ArgArg genotype was seen in patients with excessive sun exposure compared to patients with standard sun exposure (69.2 vs. 44.1 %, P = 0.02) and also compared to controls (69.2 vs. 45.9 %, P = 0.002). Individuals with TP53 ArgArg genotype and highly exposed to sunlight had 2.65 (95 % CI: 1.42-4.92)-fold increased risk for CM than others. XPC CC (27.8 vs. 10.4 %, P = 0.02) and the GSTP1 IleIle (58.3 vs. 36.8 %, P = 0.04) genotypes were more common in patients with advanced tumours than in patients with localized tumours and were also more common in these patients than in controls (27.8 vs. 6.9 %, P = 0.001; 58.3 vs. 37.0 %, P = 0.02, respectively). Individuals with the respective genotypes had 5.23 (95 % CI: 1.97-13.82)-fold and 2.38 (95 % CI: 1.13-5.01)-fold increased risks for advanced tumour than others, respectively.
Conclusion: Our data suggest that inherited abnormalities of XPC, XPF, TP53 and GSTP1 pathways of the DNA repair, apoptosis and metabolism of reactive oxygen species are important determinants of CM in individuals from south-eastern Brazil.