Background: The P53 Arg72Pro, MDM2 c.+309T>G, BAX c.-248G>A, and BCL2 c.-717C>A polymorphisms have variable roles in the apoptosis pathways.
Objective: To clarify the roles of these polymorphisms in the risk for cutaneous melanoma (CM).
Methods: Genomic DNA of 200 CM patients and 215 controls was analyzed by PCR-RFLP.
Results: In 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.
Conclusion: The 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.
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