Association of the XPD and XRCC3 gene polymorphisms with oral squamous cell carcinoma in a Northeastern Brazilian population: A pilot study

Objective to evaluate the association between XPD and XRCC3 polymorphisms and oral squamous cell carcinoma (OSCC). Design the sample consisted of 54 cases of OSCC and 40 cases of inflammatory fibrous hyperplasia (IFH). Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results XPD-Lys/Gln was more common in IFH (n = 28; 70%) than in OSCC (n = 24; 44.4%) (OR: 0.3; p < 0.05). XPD-Gln was more frequent in high-grade lesions (0.48) than in low-grade lesions (0.21) (OR: 3.4; p < 0.05). The Gln/Gln genotype was associated with III and IV clinical stages (OR: 0.07; p < 0.05). XRCC3-Met was more frequent in OSCC (0.49) than in IFH (0.35) (OR: 2.6; p < 0.05). The Met/Met genotype was associated with the presence of metastases (OR: 8.1; p < 0.05) and with III and IV clinical stages (OR: 0.07; p < 0.05). Conclusions in this sample, the frequency of XPD-Gln in IFH suggests that this variant may protect against OSCC. The presence of the XRCC3-Met allele seems to contribute to the development of OSCC, metastases and more advanced stages in these lesions.

Association of the XPD and XRCC3 gene polymorphisms with oral squamous cell carcinoma in a Northeastern Brazilian population: A pilot study

Objective to evaluate the association between XPD and XRCC3 polymorphisms and oral squamous cell carcinoma (OSCC). Design the sample consisted of 54 cases of OSCC and 40 cases of inflammatory fibrous hyperplasia (IFH). Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results XPD-Lys/Gln was more common in IFH (n = 28; 70%) than in OSCC (n = 24; 44.4%) (OR: 0.3; p < 0.05). XPD-Gln was more frequent in high-grade lesions (0.48) than in low-grade lesions (0.21) (OR: 3.4; p < 0.05). The Gln/Gln genotype was associated with III and IV clinical stages (OR: 0.07; p < 0.05). XRCC3-Met was more frequent in OSCC (0.49) than in IFH (0.35) (OR: 2.6; p < 0.05). The Met/Met genotype was associated with the presence of metastases (OR: 8.1; p < 0.05) and with III and IV clinical stages (OR: 0.07; p < 0.05). Conclusions in this sample, the frequency of XPD-Gln in IFH suggests that this variant may protect against OSCC. The presence of the XRCC3-Met allele seems to contribute to the development of OSCC, metastases and more advanced stages in these lesions.

Avaliacao de polimorfismos nos genes XPD e XRCC3 em carcinomas orais de celulas escamosas

Oral squamous cell carcinoma (OSCC) is an important cause of morbidity and mortality worldwide despite recent advances in treatment. There are several studies aiming to find markers that may improve the assessment of this disease prognosis. Studies about genetic polymorphisms have gained prominence due to their influence on individual susceptibility to cancer development. The aim of this study was to evaluate the association between the frequency of polymorphisms XPD Lys751Gln and XRCC3 Thr241Met and clinicopathological features of OSCC cases, including age, sex, presence or absence of metastases, and histological grading of malignancy according to Bryne (1998). Sample consisted of 54 cases of OSCC and 40 cases of inflammatory fibrous hyperplasia (IFH). OSCC cases were classified as low or high grade. DNA samples were previously extracted from paraffin blocks. Genotypes for each case were determined through PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism). Results were analyzed by Fisher s exact test and Chi-square test and the odds ratio was calculated considering p < 0.05 to indicate statistical significance. For XPD, Lys/Gln genotype was more common in IFHs (n=28; 70%) than in OSCCs (n=24; 44.4%) (OR: 0.3; p<0.05). Frequency of Gln allele was higher in high-grade lesions when compared to low grade lesions (0.48 and 0.21, respectively) (OR: 3.4; p<0.05). For XRCC3, Met allele was more common in OSCC than in IFH (0.49 and 0.35, respectively) (OR: 2.6; p<0.05). Met/Met genotype was associated with presence of metastases (OR: 8.1; p<0.05). There was no statistically significant association between the genotypes and the age or sex of patients. In the present sample, the higher frequency of XPD Gln allele in IFH reveals a possible protective role of this variant against the development of OSCC. However, its association with high-grade lesions indicates that this allele could influence the tumor progression after the neoplasia development. The presence of XRCC3 Met allele, in turn, seems to contribute to the development of OSCC and metastases

Estudo da resposta Th17 no transplante renal alogênico: contribuição do eixo quimiotático CCR6/CCL20 e dos polimorfismos gênicos em IL17A e IL17RA

Kidney transplantation is the best treatment for patients who have lost kidney function. Renal transplant patients require accurate immunosuppressive drugs to prevent rejection. In this process T helper cells of the immune system perform key role in the immune response to the graft, and recently the Th17 cells has been investigated by production of IL-17 potent proinflammatory cytokine whose role in the rejection has also been described. Increased of Th17 cell expression has an important association with the development of rejection in renal microenvironment, however the likely mechanism is not well understood. This study aimed to evaluate the Th17 response from the influence of the chemotactic axis CCR6/CCL20 and genetic variants in IL-17 and IL-17RA. We conducted a case-control study involving 148 patients transplanted at the University Hospital Onofre Lopes/UFRN in which assessed by immunohistochemistry protein expression of IL-17 and chemokines CCR6/CCL20 and by PCR-RFLP genetic variants in IL17A and IL17RA. Our results showed no influence of genetic polymorphisms on the outcome of the graft or the protein expression of IL-17. In renal graft microenvironment found several sources producing IL-17: tubular epithelial cells, glomerular cells, neutrophils and cell interstitial infiltration, in turn the expression of chemotactic axis CCR6/CCL20 was restricted to the tubular epithelium cells. There was a slight positive linear correlation between the presence of IL-17 and expression of chemotactic axis CCR6/CCL20 in the microenvironment of renal graft. Therefore, we believe that, combined with our results, further studies with increased "n" sample and greater control over the variables involved in obtaining the renal specimen, can determine more clearly the influence of chemotactic axis CCR6 / CCL20 and polymorphisms in cytokines related to Th17 profile on the control of this cell subtype response in rejection processes to renal allograft.