Banca de QUALIFICAÇÃO: EDILSON LEITE DE MOURA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : EDILSON LEITE DE MOURA
DATE: 19/05/2023
TIME: 10:00
LOCAL: Presencial
TITLE:

Identification of immuno/genetic biomarkers involved
In susceptibility to precancerous lesions and cervical cancer

KEY WORDS:

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

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

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 variations, which are attributed to dysregulations in cytokines and TollLike Receptors (TLRs) genes, have been associated with persistent HPV infection and cervical cancer. These dysregulations can be driven by polymorphisms in their respective genes, which can affect expression, structure and/or function protein. Therefore, the present thesis had as main objective to evaluate the influence of polymorphisms in cytokines and TLRs genes in the susceptibility to Squamous Intraepithelial Lesion (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 1, (2) systematic review with meta-analysis 2, (3) case-control study. The case-control study involved 57 cases (11 of which were HSIL and 46 of 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 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 metaanalysis 1 showed that polymorphisms in 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) genes were associated with increased risk for cervical cancer. In the systematic review with meta-analysis 2, polymorphisms in TLR4 (rs4986791, rs10759931, rs1927911) and TLR9 (rs187084, rs352140, rs5743836) genes were identified as risk factors for cervical cancer. In the case-control study, the +4221T/A genotype in the codominant (OR = 7.43 [95% CI = 1.85-29.95], p = 0.005) and overdominant (OR = 6.58 [95% CI = 1.64-26.31], p models) = 0.008); +4221T/A+A/A genotypes, in the dominant model (OR = 9.91 [95% CI = 2.56-38.42], p = 0.001) and +4221A allele (OR = 10.64 [95% CI = 2.96- 38.27] , p < 0.0001) of IL-6 +4221T>A SNP (rs13306435) were associated with increased risk for HSIL/cervical cancer. The +6703G/A genotype of TLR1 +6703G>A SNP (rs4833095), in the overdominant model, showed to increase the risk for HSIL/cervical cancer (OR = 2.55 [95% CI = 1.08-6.03], p = 0.034). 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 cytokines and TLRs genes may in the future be potential early biomarkers of cervical cancer.

BANKING MEMBERS:
Externo(a) ao Programa - 2361727 - CARLOS ALBERTO DE CARVALHO FRAGA
Presidente - 1867374 - ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
Interno(a) - 1298235 - EMILIANO DE OLIVEIRA BARRETO
Interno(a) - 1046888 - MARCIO BEZERRA SANTOS
Externo(a) ao Programa - 1697820 - VERONICA DE MEDEIROS ALVES