1122P - Inherited abnormalities in genes that during the apoptosis process and cutaneous melanoma risk

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Skin cancers
Hereditary syndromes
Presenter Cristiane Oliveira
Authors C. Oliveira1, J.A. Rinck-Junior1, G.J. Lourenco1, M.L. Cintra2, A.M. Moraes1, C.S.P. Lima1
  • 1Department Of Internal Medicine, State University of Campinas, 13083-970 - Distrito de Barão Geraldo, Campinas, São Paulo, Brazil/BR
  • 2Department Of Patology, State University of Campinas, 13083-970 - Distrito de Barão Geraldo, Campinas, São Paulo, Brazil/BR



P53 (guardian of the genome), MDM2 (p53 inhibitor), BCL2 (anti-apoptotic) and BAX (proapoptotic) genes remove cells damaged by ultraviolet (UV) rays of sunlight and, therefore, are related to the origin of cutaneous melanoma (CM). All these genes are polymorphic in humans. The Arg wild allele of the P53 Arg72Pro polymorphism is more efficient than the variant Pro allele at inducing apoptosis. The variant G and A alleles of MDM2 T309G and the BCL2 C (-948) A polymorphisms, and the variant A allele of the BAX G(-248)A polymorphism are related to higher and lower expressions of the encoded proteins, respectively, than their wild T, C and G alleles. This study aimed to clarify the roles of the above-mentioned genetic polymorphisms in the risk and clinical manifestation of the tumor.

Material and methods

In this case-control study, genomic DNA from peripheral blood of 150 consecutive CM patients (75 males and 75 females, 138 Caucasians and 12 non-Caucasians aged 20-89 years) and 150 healthy subjects, matched by age, gender and race, was analyzed by polymerase chain reaction followed by enzymatic digestion.


The frequencies of the P53 ArgArg and the BCL2 AA genotypes were higher in patients than in controls (58.7% versus 44.7%, P= 0.01) and (28.0% versus 15.3%, P= 0.004), respectively. Carriers of these genotypes had a 1.86 and 2.87-fold increased risk for CM than those with the remaining genotypes, respectively. Excesses of the P53 ArgArg plus BCL2 AA and P53 ArgArg plus BAX AA were seen in patients when compared to controls (36.1% versus 16.9%, P= 0.002) and (29.5% versus 15.3%, P= 0.008). Carriers of these genotypes had a 3.43 and 2.71-fold increased risk for CM than others, respectively.


The data suggest that P53 Arg72Pro, BCL2 C(-248)A and BAX G(-248)A polymorphisms, alone or combined, alter the risk for CM in our region. We believe that carriers of specific genotypes of the above-mentioned genes should receive additional recommendation to avoid exposition to sunlight, in addition to frequently being evaluated by a dermatologist for early disease diagnosis. Financial support: (FAPESP)


All authors have declared no conflicts of interest.