1119P - Association of Genetic Polymorphisms in Tumor Suppressors, ERP29 and PTCH1, and DNA Transcription Factors, IKBKAP and ZNF415, with Cutaneous Melanoma Risk

Abstract

ABSTRACT Introduction Recently, we found that genetic single nucleotide polymorphisms (SNPs) in tumor suppressors ERP29 c.293A > G, PTCH1 g.79755C > T and g.79456C > T, and in genes of DNA transcription IKBKAP p.Cys1072Ser and ZNF415 c.443A > G, alter the oropharynx cancer risk. The study was conducted using high resolution DNA microarrays genotyping (SNP 5.0 array, Affymetrix®) and the quantities and functions of the proteins encoded by distinct alleles are being examined by our research group. Objective: To investigate the influence of the referred SNPs in the risk of cutaneous melanoma (CM). Materials and methods Genomic DNA from 153 CM patients and 153 controls were analyzed by TaqMan® genotyping assays. The differences between groups were analyzed by the logistic regression model. Power analysis (PA) was used to verify the effect of sample size on the results obtained in the study. Results The frequencies of ERP29 c.293AA + PTCH1 g.79755CC (95.0 vs 80.1%, P=0.006; PA=86%), ERP29 c.293AA + PTCH1 g.79456CC (94.9 vs 79.4%, P=0.005; PA=88%), ERP29 c.293AA + ZNF415 c.443GG (56.2 vs 31.6%, P=0.01; PA=84%) combined genotypes were more common in patients than in controls. Individuals with the referred genotypes were under a 4.3 (95%CI: 1.61-13.43), 4.3 (95%CI: 1.63-13.49), and 3.05 (95%CI: 1.29-7.53) fold increased risk for CM than others. In addition, the frequencies of ERP29 c.293AA + PTCH1 g.79456CC + IKBKAP p.1072CysCys (98.5 vs 83.3%, P=0.01; PA=86%), ERP29 c.293AA + PTCH1 g.79456CC + ZNF415 c.443GG (85.7 vs 44.1%, P=0.004; PA=96%) combined genotypes were also higher in patients than in controls. Individuals with the referred genotypes were under a 13.5 (95%CI: 2.47-252.3) and 8.05 (95%CI: 2.21-39.24) fold increased risks for CM than others. Conclusions Our data present for the first time that: 1) ERP29 c.293A > G, PTCH1 g.79755C > T and g.79456C > T, IKBKAP p.Cys1072Ser, and ZNF415 c.443A > G SNPs are important inherited risk factors for CM and; 2) healthy individuals with these SNPs should receive recommendation to avoid sunlight exposition and should be frequently evaluated by a dermatologist to perform an early diagnosis of the tumor. Financial support: FAPESP and FINEP. Disclosure All authors have declared no conflicts of interest.