1117P - XPC, XPF and P53 polymorphisms associated with DNA repair and prognosis in cutaneous melanoma

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Melanoma and other Skin Tumours
Translational Research
Presenter Gabriela Gomez
Citation Annals of Oncology (2014) 25 (suppl_4): iv374-iv393. 10.1093/annonc/mdu344
Authors G.V.B. Gomez, C. Oliveira, J.A. Rinck-Júnior, A.M. Moraes, C.S.P. Lima
  • Department Of Internal Medicine, Faculty of Medical Sciences, University of Campinas, SP - Sao Paulo/BR

Abstract

Aim

XPC, XPF and P53 genes act on nucleotide excision repair of ultraviolet radiation-induced DNA damage and are involved in cutaneous melanoma (CM) development. The DNA repair ability is variable in humans.Variant C and wild Arg alleles of XPC A2920C and P53 Arg72Pro polymorphims encode proteins with lower activities in DNA repair than those encoded by other alleles, respectively. Variant C allele of XPF T30028C influences mRNA stability and affects levels of protein expression. This study aimed to evaluate whether these polymorphisms are associated with relapse-free survival (RFS) and overall survival (OS) of CM patients.

Methods

We analyzed 232 CM patients diagnosed from 1989 to 2013 at a University Hospital. Genomic DNA of patients was analyzed by polymerase chain reaction, and enzymatic digestion, for discrimination of pertinent genotypes. RFS and OS were calculated using the univariate Kaplan-Meier estimate probabilities, and differences between survival curves were analyzed by the log-rank test. OS was calculated from the date of diagnosis until the date of death or last follow-up.

Results

The median period of observation of patients in the study was 57 months (range: 1-285). At 60 months of follow-up, we observed that RFS of patients with XPF TT + TC genotypes was higher than that found in patients with CC genotype (73% vs 30%, P = 0.007). At this time, RFS was also higher in patients with XPF TT + TC plus P53 ArgPro + ProPro genotypes than in those with XPF CC plus P53 ArgArg genotypes (74% vs 19%, P = 0.004). At 120 months of follow-up, we observed that OS of patients with XPF TT + TC genotypes was higher than that observed in patients with CC genotype (86% vs 63%, P = 0.05). OS of patients with XPF TT + TC plus P53 ArgPro + ProPro genotypes was also higher than that found in patients with XPF CC plus P53 ArgArg genotypes (89% vs 68%, P = 0.07) at this time. In contrast, RFS and OS were worse in patients with Breslow thickness ≥1.5 mm (87% vs 52%, P = 0.0001; 88% vs 79%, P = 0.008), Clark level IV + V (79% vs 60%, P = 0.004; 86% vs 78%, P = 0.02) and advantage stage III + IV (77% vs 48% P = 0.0001; 88% vs 66% P = 0.0001), respectively.

Conclusions

The data found herein provide evidence, for the first time, that inherited abnormality in DNA repair pathway related to XPF and P53 polymorphisms influence RFS and OS in CM patients.

Disclosure

All authors have declared no conflicts of interest.