Associação entre o polimorfismo Thr399Ile do gene TLR-4 e a susceptibilidade ao câncer de próstata

Abstract

Prostate cancer (PCa) is the second most common tumor in men and the second leading cause of death from cancer in this group. The discovery of biomarkers can contribute to early diagnosis, increasing the chances of cure and directing new therapeutic strategies. Genetic polymorphisms are essential in defining risk groups, whether related to therapeutic resistance or to the development of chronic diseases such as cancer. Toll-like receptors (TLRs) are innate immunity receptors that activate pro-inflammatory signaling pathways in response to intracellular damage or patterns associated with pathogens. The TLR4 receptor recognizes lipopolysaccharides, but is also related to the development of tumors. Our aim was to evaluate the Thr399Ile polymorphism of the TLR4 gene and its association with the risk of PCa occurrence. Twenty-nine patients with PCa and 22 with benign prostatic hyperplasia (BPH), genotyped by PCR-RFLP, were analyzed using the enzyme Hinf I. The genotypes found were normal homozygous-CC (16 with PCa and 11 with BPH), mutant homozygous-TT (10 with PCa and 10 with BPH) and heterorygous-CT (3 with PCa and 1 with BPH). However, in both groups, the genotypes were not in Hardy-Weinberg equilibrium. In addition, genotypic frequencies were not statistically different between individuals with PCa and BPH without correlation with clinical and anatomopathological data such as PSA (Prostatic-Specific Antigen), Gleason score and TNM. For the allelic distribution, the C allele was more frequent in patients with PCa, however without statistical significance. Studies with a larger number of participants and functional tests are needed to elucidate the role of this polymorphism in PCa.