Influence of polymorphisms in JAK/STAT pathway genes on the susceptibility and cli...
| Grant number: | 14/10042-5 |
| Support type: | Scholarships in Brazil - Master |
| Effective date (Start): | August 01, 2014 |
| Effective date (End): | February 29, 2016 |
| Field of knowledge: | Health Sciences - Medicine |
| Cooperation agreement: | Coordination of Improvement of Higher Education Personnel (CAPES) |
| Principal Investigator: | Carmen Silvia Passos Lima |
| Grantee: | Gabriela Vilas Bôas Gomez |
| Home Institution: | Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
Abstract Cutaneous Melanoma (CM) is noteworthy among neoplasms due to its high metastatic potential and refractory to therapy. Under physiological conditions, abnormal melanocytes can be eliminated from the body by cytokines produced by T lymphocytes. The process is regulated by PD1, PDL-1 and PDL-2. The PDCD1 gene encoding the receptor PD1 on T lymphocytes, which have as ligands PDL-1 and PDL-2 of antigen-presenting cells, dendritic cells. When PD1 binds to the PDL-1 and PDL-2, inhibition of proliferation and release of cytokines by T lymphocytes, which favors the survival of abnormal melanocytes. Abnormal melanocytes may also express the ligand PDL-1 circumventing the immune system and consequent survival. The PDCD1 gene is polymorphic in humans and thus can inherit healthy individuals distinct abilities to eliminate abnormal melanocytes. The aim of the present study are to investigate whether the PD1.1 c.-606G>A (rs36084323), c.627+252C>T (rs41386349), with no specific denomination, PD1.5 (rs2227981, c.804T>C) and PD1.9 (rs2227982, c.644C>T) polymorphisms of PDCD1 gene influence the risk of CM, the clinical and biological manifestations of the tumor and the expression of the gene PDCD1. 250 patients with MC and 250 controls will be evaluated. Clinical information will be obtained from patients for access to medical records. The genotypes of PD1.1 polymorphisms (rs36084323, c.-606G>A), PD1.5 (rs2227981, c.804T>C), PD1.9 (rs2227982, c.644C>T) and rs41386349, c.627+252C>T with no specific denomination, PDCD1 gene, will be performed on peripheral blood leukocytes by polymerase chain reaction in real time chain. The expression of the gene PDCD1 and concentration of protein PD1 in peripheral blood lymphocytes of 60 healthy controls (20 wild homozygous, 20 heterozygous and 20 homozygous variants) are evaluated by quantitative PCR and flow cytometry, respectively. The statistical significance of differences between groups will be calculated using the exact probability test or Fisher's chi-square. Determination of the risk of occurrence of MC in patients and controls were submitted, shall be obtained by means of the Odds Ratios (ORs). Comparisons of gene expression in individuals with different genotypes of each gene polymorphism will be carried through thee ANOVA (Analysis of Variance) or the Mann-Whitney test. Have the results will be analyzed by cytometry BDFACSDiva software. We believe the results of this study will contribute to a better understanding of the pathophysiology of CM and to identify individuals at high risk for the disease, which deserve to receive special attention in prevention and early diagnosis. (AU) | |