Análise do polimorfismo no gene do receptor TLR9(RS187084) em pacientes com câncer de colo uterino

Abstract

Cervical cancer (CC) corresponds to the third most prevalent type in Brazil, as well as the fourth cause of death among women. Its development is linked to persistent infection with high-risk subtypes of the Human Papillomavirus (HPV), but a minority of virus carriers develop cancer. Among the immunological factors involved in this progression are Toll-like receptors (TLR). Polymorphisms that generate deletions in TLR9 may be related to greater susceptibility and disease progression. The current research aimed to evaluate the relationship between the presence of the polymorphism in the TLR9 receptor (allele rs187084) in women diagnosed with CC, as well as its association with disease outcomes. It was an observational and prospective, case-control study. Mouth brush samples were collected from 83 women, 43 cases and 40 healthy controls. The tissue samples obtained were preserved for subsequent extraction of genomic DNA and performance of the PCR technique using a specific protocol. An interview and medical record analysis were also carried out to compare epidemiological data, information on the presentation of the disease and its characteristics, evaluation of the chosen treatments, as well as oncological follow-up to analyze the outcomes. The average age was 46 years old and the majority were asymptomatic at diagnosis. Other sociodemographic findings were also consistent with the national literature described. The histological type of squamous cell carcinoma (SCC) was the predominant one with 40 cases and the majority of women were diagnosed in stage I/II, with a predominance of stage IIB (parametrial involvement). Because of this, trimodal treatment based on radiotherapy was the choice in the majority, with 36 cases, with surgery being an option initially in 9 cases. The recurrence rate was high (34.2%) with 13 patients, in a mean follow-up period of 36.5 months. In the polymorphism analysis, its presence did not increase the risk of cancer (p=0.749), but patients with SCC presented more T/C and TT genotypes (p=0.044). The presence of T/C heterozygosity was more associated with trimodal treatment, in other words, more advanced disease, and the presence of TT homozygosity was more related to liver progression. Due to the low death rate (05 cases), it was not possible to compare Overall Survival, but when evaluating the progression-free Survival curve, it was worse in the Heterozygous T/C group (p=0.031). In conclusion, this study suggested that, in our population, this polymorphism cannot be associated with an increased risk of CC. However, the T/C and TT genotypes seem to be more present in patients who have already progressed to cancer, as well as being related to worse progression-free Survival and liver recurrence, respectively.