Genetic polymorphisms on PDCD1 gene, regulator of lymphocyte activity, in cutaneous melanoma susceptibility

Author(s)

Gabriela Vilas Bôas Gomez

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2016-03-23

Examining board members

Carmen Silvia Passos Lima; Roger Chammas; Paulo Eduardo Neves Ferreira Velho

• Advisor: Carmen Silvia Passos Lima

Abstract

Abnormal melanocytes can be eliminated from the body by T lymphocytes. The PDCD1 gene encoding the receptor PD1 on T cells is related to the immune system regulation, and it is polymorphic in humans. Thus, it is possible for healthy individuals to inherit different abilities for eliminating abnormal melanocytes and developing cutaneous melanoma (CM). This study aimed to assess whether the single nucleotide polymorphisms (SNPs) PD1.1 c.-606G>A, PD1 c.627+252C>T, PD1.5 c.804C>T and PD1.9 c.644C>T of PDCD1 gene influence the risk of CM, clinical and biological manifestations of the tumor, expression of PDCD1 gene, and survival of patients with CM. We evaluated 250 patients with CM and 250 controls (blood donors). Genotypes of SNPs were identified in DNA from peripheral blood leukocytes, by real-time polymerase chain reaction (PCR). The PDCD1 gene expression was assessed by quantitative PCR. The statistical significance of differences between groups was calculated using the Fisher's exact or chi-square test. The occurrence of CM risks in patients and controls, was accessed by the odds ratios (ORs). Comparisons of gene expression in individuals with different genotypes for each SNP were performed using the Mann-Whitney test. The recurrence-free survival (RFS) and overall (OS) of patients were evaluated by the Kaplan-Meier method/log-rank test, univariate and multivariate analyses of Cox. Individuals with CC genotype PD1 isolated and associated with PD1.5 CC genotype were under 2.20 and 2.51 times greater risk of developing CM than others, respectively. Indivíduas with I or II fototype and the PD1 CC genotype and CC + CC of PD1 e PD1.5 SNPs were under 5.89 times and 6.71 times greater risks of developing CM than others. PD1.5 TT genotype was associated with increased expression of PDCD1 gene than CT or CC genotype (1.28 versus 2.49 UA; p= 0.03). Patients with PD1.1 AA genotype had lower RFS than those with GA or GG genotypes. We believe that our results may help to identify individuals at high risk of developing CM and tumor patients with poor prognosis, deserving special attention in prevention, early diagnosis and differentiated treatment (AU)

• FAPESP's process: 14/10042-5 - Influence of the PDCD1 polymorphisms, related to activity of T lymphocytes, in gene expression and susceptibility to cutaneous melanoma
• Grantee: Gabriela Vilas Bôas Gomez
• Support Opportunities: Scholarships in Brazil - Master