Análise da associação dos polimorfismos TNFA -308 G>A (rs1800629), IL-10 -819 C>T (rs1800871) com a susceptibilidade ao câncer cervical em mulheres infectadas pelo HPV em uma amostra da população de Alagoas, Brasil

Abstract

Human Papillomavirus (HPV) is considered the most common Sexually Transmitted Infection (STI) in the world. This infection represents a significant global public health problem due to its etiological potential in the development of several types of human cancers, such as cervical cancer. Immunological variations of the host have been associated with susceptibility to Cervical Intraepithelial Neoplasms (NIC) and cervical cancer. These immunological variations may be attributed to Simple Nucleotide Polymorphisms (SNPs) present in the cytokine genes. Therefore, the present study aimed to evaluate the influence of polymorphisms present in TNFA (-308G> A) and IL-10 (-819C> T) genes on susceptibility to cervical cancer in HPV-infected women in the Alagoas, Brazil. This is a case-control study involving 45 women diagnosed with cervical cancer and HPV positive, and 93 clinically healthy controls with normal cytopathologic and HPV negative. Viral detection was performed through nested Polymerase Chain Reaction (nPCR) using the primers MY09/MY11 and GP5+/GP6+ located in L1 region of HPV. Polymorphism analysis was performed using the real-time Polymerase Chain Reaction (PCR) technique, using TaqMan probes by the allelic discrimination method. The results showed that the C/T genotype in the codominant model (p = 0.035, OR with 95% CI = 2.52 [1.07-5.97]) and the -819C/T+TT genotypes in the dominant model (p = 0.037; % CI = 2.41 [1.06-5.50]) of IL-10-819C>T SNP were associated with increased risk for developing cervical cancer in HPV-infected women. In the meta-analysis, the IL-10 -819C>T SNP showed a similar result to that of the Alagoana population, on what the -819C/T+TT genotypes in the dominant model were identified as a risk factor for the development of Squamous Intraepithelial Lesion (SIL) in HPV infection (p = 0.01, OR at 95% CI = 1.76 [1.13-2.74]). There was no significant association between TNFA -308G>A SNP and cervical cancer in the population of Alagoas. However, in the meta-analysis, performed with other populations, the genotype -308G/G in the codominant model was associated with protective effect for cervical cancer (p = 0.0009; OR with 95% CI = 0.79 [0.69-0.91]) . While the G/A+A/A genotypes in the dominant model were associated with increased risk for SIL in HPV infection (p = 0.04, OR at 95% CI = 1.69 [1.01-2.82]). In conclusion, carriers of the T allele in the SNP IL-10-819C>T showed increased risk for cervical cancer in the population of Alagoas, Brazil, and that was corroborated with the result meta-analysis of other populations. TNFA -308G>A SNP was no associated with cervical cancer in the Alagoana population. However, the -308G/G genotype was associated with protection against cervical cancer, and carriers of the A allele (-308G/A+A/A) were associated with increased risk for SIL in HPV infection at the meta-analysis of other populations.