Banca de DEFESA: ANDREIA MICHELLE ALVES CUNHA DE ALCÂNTARA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : ANDREIA MICHELLE ALVES CUNHA DE ALCÂNTARA
DATE: 10/12/2025
TIME: 13:30
LOCAL: Departamento de Biologia
TITLE:

 

 

 

KEY WORDS:

Cervical cancer. Human papillomavirus (HPV). Genetic polymorphisms.
DNA repair genes; Cervical lesions.

 

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

Cervical cancer (CCU) continues to negatively impact women’s health, with an estimated 350,000 deaths per year worldwide. Although human papillomavirus (HPV) is the main etiological agent of the disease, single nucleotide polymorphisms (SNPs) in genes involved in deoxyribonucleic acid (DNA) repair and cell cycle control may influence susceptibility to HPV infection and the progression of cervical lesions to CCU, but the impact of these SNPs differs among populations. Thus, the aim of this study was to investigate the association of the SNPs X-ray Repair Cross Complementing 1 (XRCC1, Arg399Gln, rs25487), Tumor Protein p53 (TP53, Arg72Pro, rs1042522), Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A, Ser31Arg, rs1801270), and Cyclin-Dependent Kinase Inhibitor 1B (CDKN1B, Val109Gly, rs2066827) with susceptibility to HPV infection and progression of cervical lesions in women from the state of Pernambuco (PE). To this end, an analytical observational case–control study was conducted, including 581 women. Paraffin-embedded uterine tissues from 282 women (experimental group) with a history of HPV infection, cervical lesions and/or CCU, obtained from the Municipal Public Health Laboratory of the Health Secretariat of Recife (LMSP/SS – Recife-PE), and cervicovaginal smears from 299 women (control group) without a history of HPV infection, cervical lesions or CCU, obtained from the biobank of the Federal Rural University of Pernambuco (UFRPE), were analyzed. XRCC1 (rs25487) and TP53 (rs1042522) SNPs were analyzed using the mismatch amplification mutation assay (MAMA-PCR) technique, and CDKN1A (rs1801270) and CDKN1B (rs2066827) SNPs using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). The results were evaluated as follows: (I) univariate analysis – genotypes GA (XRCC1) (OR = 3.89; 95% CI = 2.569–5.890; p < 0.0001), GC (TP53) (OR = 2.45; 95% CI = 1.632–3.687; p < 0.0001), and AA (CDKN1A) (OR = 3.87; 95% CI = 2.455–6.113; p < 0.0001) revealed an increased risk for susceptibility to HPV infection, whereas the mutant GG (CDKN1B) (OR = 0.36; 95% CI = 0.236–0.537; p < 0.0001) showed a protective effect. For the outcome of cervical lesions, only XRCC1 (rs25487) and TP53 (rs1042522) SNPs showed significant associations: AA (XRCC1) (OR = 36.00; 95% CI = 15.347–84.449; p < 0.0001) conferred increased risk, whereas CC (TP53) (OR = 0.049; 95% CI = 0.023–0.103; p < 0.0001) had a protective effect. (II) Analysis by skin color and age group: a significant association was observed only among women in the case group. The GA/AA variants of XRCC1 were more frequent among Black women and those aged ≥50 years. Black women showed lower odds of carrying GG than White women (OR = 0.045; 95% CI: 0.016–0.127; p < 0.0001), and the same pattern was observed for women aged ≥50 years compared with younger women (OR = 0.0516; 95% CI: 0.018–0.146; p < 0.0001), indicating an accumulation of GA/AA genotypes in these strata, with GG as the reference genotype. (III) Combined genotype analysis (cases vs. controls, for cervical lesion progression) showed that GA+AA/GG (XRCC1/TP53) was associated with increased risk (OR = 1.62; 95% CI = 1.021–2.566; p = 0.04), whereas the double wild-type GG/GG (XRCC1/TP53) (OR = 0.05; 95% CI = 0.022–0.102; p < 0.0001) showed a protective effect; combinations GA+AA/CC (XRCC1/CDKN1A) (OR = 0.22; 95% CI = 0.121–0.386; p < 0.0001), GG/CA+AA (XRCC1/CDKN1A) (OR = 0.22; 95% CI = 0.145–0.322; p < 0.0001), and the double wild-type GG/CC (XRCC1/CDKN1A) (OR = 0.11; 95% CI = 0.057–0.218; p < 0.0001) showed a protective effect; genotypes GA+AA/TT (XRCC1/CDKN1B) (OR = 2.36; 95% CI = 1.470–3.779; p < 0.0001) were associated with increased risk, whereas the combination GG/TG+GG (XRCC1/CDKN1B) (OR = 0.20; 95% CI = 0.120–0.333; p < 0.0001) showed a protective effect; combinations CA+AA/GG (CDKN1A/TP53) (OR = 0.42; 95% CI = 0.287–0.611; p < 0.0001), CC/GC+CC (CDKN1A/TP53) (OR = 0.24; 95% CI = 0.132– 0.428; p < 0.0001), and the double wild-type CC/GG (CDKN1A/TP53) (OR = 0.18; 95% CI = 0.094–0.338; p < 0.0001) showed a protective effect; the combination TT/CA+AA (CDKN1B/CDKN1A) (OR = 0.33; 95% CI = 0.171–0.633; p < 0.0001) was protective against lesions, whereas TG+GG/CC (CDKN1B/CDKN1A) (OR = 3.03; 95% CI = 2.051–4.477; p < 0.0001) was associated with increased risk; the double wild-type TT/GG (CDKN1B/TP53) (OR = 0.46; 95% CI = 0.289–0.725; p < 0.0001) showed a protective effect, whereas the combination TG+GG/GG (CDKN1B/TP53) (OR = 2.41; 95% CI = 1.507–3.867; p < 0.0001) was associated with increased risk. (IV) Analysis of allelic interactions among XRCC1 (rs25487), TP53 (rs1042522), and CDKN1A (rs1801270) showed that the combinations A-G-A (OR = 6.36; 95% CI = 3.21–12.60; p = 1.1×10⁻⁷) and A-G-C (OR = 2.09; 95% CI = 1.44–5.86; p = 0.0029) were associated with an increased risk of cervical lesions, whereas the combinations G-G-A and G-GC had a protective effect. The findings of this study suggest that these SNPs may act as risk or protective biomarkers. This work provides data with the potential to advance scientific knowledge and contribute to improving strategies for the prevention and screening of HPV infection, the progression of cervical lesions, and the treatment of CCU, aiming to improve quality of life and increase the chances of cure for affected women.

COMMITTEE MEMBERS:
Presidente - PAULO ROBERTO ELEUTERIO DE SOUZA
Interno - JOSE WILTON PINHEIRO JUNIOR
Interno - PABYTON GONCALVES CADENA
Externa à Instituição - AMANDA EMMANUELLE SALES CONNIFF
Externa à Instituição - MARIA DE MASCENA DINIZ MAIA - UFRPE