Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)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), BM 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. (C) 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.742135141Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2009/12602-0, 2010/18904-5]