Banca de DEFESA: EDILSON LEITE DE MOURA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : EDILSON LEITE DE MOURA
DATE: 31/07/2023
TIME: 11:00
LOCAL: ICBS
TITLE:

INFLUENCE OF POLYMORPHISMS IN CYTOKINE AND TLRS GENES IN SUSCEPTIBILITY TO SQUAMOUS INTRAEPITHELIAL LESION AND CERVICAL CANCER: META-ANALYSES AND A CASE-CONTROL STUDY IN A SAMPLE FROM ALAGOAS, BRAZIL

KEY WORDS:

Polymorphism, Cytokines, Toll-Like Receptors, High-grade squamous intraepithelial lesion, Cervical cancer

PAGES: 197
BIG AREA: Ciências Biológicas
AREA: Genética
SUMMARY:

The high-risk Human Papillomavirus (HPV) is considered the main etiological agent of cervical cancer, however, most of these infections are spontaneously eliminated by the host's immune system. Therefore, HPV is a necessary but not sufficient factor for the development of cervical cancer. Host immune dysfunctions, which are attributed to dysregulations in cytokine molecules and Toll-Like Receptors (TLRs), have been associated with persistent HPV infection and cervical cancer. These dysregulations can be driven by polymorphisms in their respective genes and can affect protein expression, structure and/or function. Therefore, the main objective of this thesis was to evaluate the role of polymorphisms in cytokine and TLRs genes in the development of SIL and cervical cancer, through two systematic reviews with meta-analysis and a case-control study in the population of Alagoas, Brazil. The study was divided into 3 main parts: (1) systematic review with meta-analysis of polymorphisms in cytokines genes and SIL/cervical cancer, (2) systematic review with meta-analysis of polymorphisms in TLRs genes and cervical cancer, (3) study of case-control in the population of Alagoas. The case-control study involved 57 cases (11 High-grade Intraepithelial Lesion - HSIL and 46 cervical cancer) and 67 clinically healthy controls. The detection of HPV was performed using the technique of nested Polymerase Chain Reaction (nPCR) with primers MY09/MY11 and GP5+/GP6+ from the L1 region of HPV. Genotyping of polymorphisms was obtained through real-time PCR, using TaqMan probes, through the allelic discrimination method. The results of the systematic review with meta-analysis of polymorphisms in cytokine genes and SIL/cervical cancer, showed that polymorphisms in the TNFA (rs361525, rs1800629), IL-1B (rs16944), IL-6 (rs1800795), IL-10 (rs1800896) , IL-12A (rs568408), IL-12B (rs3212227), IL-17A (rs2275913, rs3748067), IL-17F (rs763780) were associated with increased risk for cervical cancer. In the systematic review with meta-analysis of polymorphisms in TLR genes and cervical cancer, polymorphisms in the TLR4 (rs4986791, rs10759931, rs1927911) and TLR9 (rs187084, rs352140, rs5743836) genes were identified as risk factors for cervical cancer. In the case-control study, the heterozygous genotype +4221T/A in the codominant and overdominant models; the +4221T/A+A/A genotypes in the dominant model and the +4221A allele of the Single nucleotide polymorphism (SNP) IL-6 +4221T>A (rs13306435) were associated with increased risk for HSIL/cervical cancer. The +6703T/C heterozygous genotype of the TLR1 SNP +6703T>C (rs4833095), in the overdominant model, has been shown to increase the risk for HSIL/cervical cancer. There was no significant association of TLR4 +8552A>G (rs4986790) and TLR9 -1486A>G (rs187084) SNPs with HSIL/cervical cancer. In conclusion, the present study identified that polymorphisms in cytokine and TLR genes can affect the phenotype of their respective genes and contribute to the development of HSIL or cervical cancer.

 

BANKING MEMBERS:
Presidente - 1867374 - ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
Interno(a) - 2151027 - ALEXANDRE URBAN BORBELY
Interno(a) - 1544773 - TIAGO GOMES DE ANDRADE
Externo(a) ao Programa - 1697820 - VERONICA DE MEDEIROS ALVES
Externo(a) à Instituição - GUILHERME BENJAMIN BRANDAO PITTA