Banca de QUALIFICAÇÃO: ANDREIA MICHELLE ALVES CUNHA DE ALCÂNTARA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : ANDREIA MICHELLE ALVES CUNHA DE ALCÂNTARA
DATE: 31/03/2025
TIME: 10:00
LOCAL: video conferência
TITLE:

Investigation of polymorphisms in tumor suprressor and DNA repair genes in patients with cervical lesions and cervical.

 

 

KEY WORDS:

Cervical Cancer, Human Papillomavirus (HPV), Genetic Polymorphisms, Tumor Suppressor Genes, DNA Repair Genes.

PAGES: 70
BIG AREA: Ciências Biológicas
AREA: Genética
SUBÁREA: Genética Humana e Médica
SUMMARY:

Cervical cancer is one of the main public health challenges, ranking as the fourth most common type of cancer among women worldwide. In Brazil, it is the third most incident cancer and the fourth leading cause of death from female neoplasms. Although Human Papillomavirus (HPV) infection is the primary etiological factor of the disease, the literature suggests that the interaction between genetic and environmental factors may significantly influence the progression of Cervical Intraepithelial Neoplasia (CIN) to cancer. Among the genetic factors involved, functional polymorphisms in genes related to DNA repair and cell cycle regulation stand out, such as X-ray Repair Cross Complementing 1 (XRCC1, rs25487), Tumor Protein TP53 (TP53, rs1042522), Cyclin-Dependent Kinase Inhibitor 1A (p21, Cip1, CDKN1A, rs1801270), and Cyclin-Dependent Kinase Inhibitor 1B (p27, Kip1, CDKN1B, rs2066827). However, the impact of these genetic variations on the predisposition to CIN and cervical cancer is not yet fully elucidated and may vary across populations. Given this context, the objective of this study was to investigate the possible association between these genetic polymorphisms and the development of CIN and cervical cancer in women from the state of Pernambuco, Brazil. This observational analytical case-control study included 581 women from the city of Recife, Pernambuco. Of these, the experimental group consisted of 282 women diagnosed with cervical lesions or cancer, while the control group comprised 299 healthy women with no history of cervical lesions or cancer. The samples analyzed included paraffin-embedded cervical tissue for the cervical lesion/cancer group and vaginal secretion samples for the healthy control group. All sample collections were conducted at the Municipal Public Health Laboratory of the Recife Health Department (LMSP/SS - Recife-PE). Two single nucleotide polymorphisms (SNPs) were analyzed using the Mismatch Amplification Mutation Assay Polymerase Chain Reaction (MAMA-PCR) technique: the Gln399Arg (A/G) polymorphism in the XRCC1 gene (X-ray repair cross-complementing protein 1, rs25487) and the Arg72Pro (G/C) polymorphism in the TP53 gene (tumor protein p53, rs1042522). The results indicated that the XRCC1 polymorphism showed a significant difference between the cervical lesion/cancer group and the healthy control group (p < 0.001). The genotypic frequency distribution in the study group was 28.17% GG, 35.46% AA, and 36.17% GA, while in the control group, it was 60.20% GG, 20.07% AA, and 19.73% GA. Individuals carrying the GA and AA genotypes had a 3.82-fold increased risk of developing cervical lesions/cancer compared to those with the GG genotype (95% CI = 2.70–5.41; p = 1.24 × 10⁻¹⁴). Regarding the TP53 polymorphism, the genotypic frequency distribution in the study group was 39.01% GG, 28.37% GC, and 32.62% CC, whereas in the control group, the distribution was 23.75% GG, 19.40% GC, and 56.86% CC, also showing a significant difference (p < 0.01). Individuals carrying the CG and CC genotypes had a 2.06-fold increased risk of developing cervical lesions/cancer compared to those with the GG genotype (95% CI = 1.47–2.87; p = 1.68 × 10⁻⁵). These findings suggest an association between XRCC1 and TP53 polymorphisms and the development of cervical cancer in the studied population, indicating their potential role as biomarkers for the disease.

COMMITTEE MEMBERS:
Presidente - PAULO ROBERTO ELEUTERIO DE SOUZA
Interno - JOSE WILTON PINHEIRO JUNIOR
Externa ao Programa - 384063 - MARIA DE MASCENA DINIZ MAIA - UFRPE