Association between genetic polymorphisms in apoptosis-related genes and risk of cutaneous melanoma in women and men

Abstract

BackgroundThe P53 Arg72Pro, MDM2 c.+309T>G, BAX c.–248G>A, and BCL2 c.–717C>A polymorphisms have variable roles in the apoptosis pathways. ObjectiveTo clarify the roles of these polymorphisms in the risk for cutaneous melanoma (CM). MethodsGenomic DNA of 200 CM patients and 215 controls was analyzed by PCR–RFLP. ResultsIn women, the frequencies of BAX GG (83.0% vs. 71.0%, P=0.04), BCL2 AA (32.0% vs. 15.0%, P=0.003), P53 ArgArg plus BAX GG (84.9% vs. 63.2%, P=0.01), P53 ArgArg plus BCL2 AA (37.0% vs. 13.1%, P=0.003), BAX GG plus BCL2 AA (70.3% vs. 33.3%, P=0.001), MDM2 GG plus BAX GG plus BCL2 AA (27.3% vs. 3.7%, P=0.03), and P53 ArgArg plus MDM2 GG plus BAX GG plus BCL2 AA (33.3% vs. 5.6%, P=0.04) genotypes were higher in patients than in controls. Female carriers of the respective genotypes were under 1.98 (95% CI: 1.01–3.91), 2.87 (95% CI: 1.43–5.77), 3.48 (95% CI: 1.34–9.04), 4.23 (95% CI: 1.63–10.96), 6.04 (95% CI: 2.10–17.37), 25.61 (95% CI: 1.29–507.24), and 25.69 (95% CI: 1.11–593.59)-fold increased risks for CM than others, respectively. In men, the frequencies of BCL2 CA+AA (83.0% vs. 67.6%, P=0.01) and MDM2 TG+GG plus BCL2 CA+AA (94.2% vs. 68.3%, P=0.003) genotypes were higher in patients than in controls. Male carriers of the respective genotypes were under 2.43 (95% CI: 1.23–4.82) and 9.22 (95% CI: 2.16–39.31)-fold increased CM risks than others, respectively. ConclusionThe data suggest for the first time that P53 Arg72Pro, MDM2 c.+309T>G, BAX c.–248G>A, and BCL2 c.–717C>A polymorphisms, enrolled in apoptosis pathways, constitute distinct determinants of CM in women and men.