Cristiane Oliveira1, Gustavo Jacob Lourenço1, José Augusto Rinck-Junior1, Maria Letícia Cintra2, Aparecida Machado Moraes3, Carmen Silvia Passos Lima4. 1. Clinical Oncology Service, Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas, Campinas, São Paulo, Brazil. 2. Pathology Dermatology Service, Faculty of Medical Sciences, Department of Anatomical Pathology, University of Campinas, Campinas, São Paulo, Brazil. 3. Dermatology Service, Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas, Campinas, São Paulo, Brazil. 4. Clinical Oncology Service, Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas, Campinas, São Paulo, Brazil. Electronic address: carmenl@fcm.unicamp.br.
Abstract
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.
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.
Authors: Cristiane Oliveira; Gustavo Jacob Lourenço; José Augusto Rinck-Junior; Aparecida Machado de Moraes; Carmen Silvia Passos Lima Journal: Med Oncol Date: 2017-01-03 Impact factor: 3.064