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


CONCLUSIONS
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.
Clinical Oncology Service, Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas, Campinas, São Paulo, Brazil.
Cristiane
C
Oliveira
Clinical Oncology Service, Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas, Campinas, São Paulo, Brazil.
Gustavo Jacob
GJ
Lourenço
Clinical Oncology Service, Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas, Campinas, São Paulo, Brazil.
José Augusto
JA
Rinck-Junior
Pathology Dermatology Service, Faculty of Medical Sciences, Department of Anatomical Pathology, University of Campinas, Campinas, São Paulo, Brazil.
Maria Letícia
ML
Cintra
Dermatology Service, Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas, Campinas, São Paulo, Brazil.
Aparecida Machado
AM
Moraes
Clinical Oncology Service, Faculty of Medical Sciences, Department of Internal Medicine, University of Campinas, Campinas, São Paulo, Brazil. Electronic address: carmenl@fcm.unicamp.br.
Carmen Silvia Passos
CS
Lima
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D016158:Genes, p53; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects; D055815:Young Adult; D051028:bcl-2-Associated X Protein / Q000235:genetics*
D051028:bcl-2-Associated X Protein; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
Apoptosis; Genetic polymorphisms; Melanoma; Risk