These results can help individualize treatment according to a patient's genetic markers. We demonstrated that ATM IVS62 + 60G>A, TGFβ 29C>T, TGFβ-509C>T, and BCL2-938C>A can function as biomarkers of tumor radiosensitivity, being candidates for a predictive genetic profile of radiotherapy response.
ABSTRACT. Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients.
ABSTRACT. The aims of this study were to analyze the polymorphisms XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPC Lys939Gln, ERCC1 Asn118Asn, and RAD51 -98G>C and to verify their influence on radiotherapy response and prognosis of patients with head and neck squamous cell carcinoma (HNSCC). Peripheral blood DNA was extracted from 311 patients and analyzed by PCR-RFLP. Our results showed that in irradiated oral and oropharyngeal patients, the 939Gln allele increased 6-fold local disease relapse risk (OR = 6.04; CI = 1.47-24.88) and over 2-fold the earliness of relapse (HR = 2.63; CI = 1.04-6.70). As for the XRCC3 polymorphism, multivariate analysis showed that the 241Met allele increases over 33-fold local relapse risk (OR = 33.64; CI = 3.23-350.85), over 12-fold earliness of relapse (HR = 12.55; CI = 2.47-63.73) and over 3-fold earliness of death (HR = 3.04; CI = 1.08-8.61). For polymorphism RAD51 -98, multivariate analysis showed that allele C increases over 3-fold the risk of relapse (OR = 3.13; CI = 1.12-8.78) and over 2-fold the earliness of relapse (HR = 2.84; CI = 1.25-6.47). For polymorphism XRCC1 Arg399Gln, multivariate analysis showed that the 399Gln allele increased the risk of local disease relapse for irradiated oral and oropharyngeal patients (OR = 3.35; CI = 1.10-10.13) by over 3-fold. Based on these results, we suggest that these polymorphisms may be useful markers of prognosis in HNSCC.
ABSTRACT. Death-associated protein 1 (DAP1) is a member of the DAP family. Its expression is associated with cell growth and normal death of the neoplastic cells, regulated by the mammalian target of the rapamycin protein. Activated DAP1 negatively regulates autophagy, which has been associated with the development and progression of several diseases, such as cancer, and with prognosis and survival of diverse tumor types. Therefore, in this study we analyzed DAP1 expression in 54 oral squamous cell carcinoma tumor samples and in 20 non-tumoral margins by immunohistochemistry. The results showed that DAP1 is more frequently expressed in tumor tissues compared with marginal non-tumoral cells. Additionally, high DAP1 expression is associated with a 4-fold increase in the risk of lymph node metastases. Our results suggest that the DAP1 protein can be used as a potential marker of lymph node metastases predisposition, helping define the best therapy for each patient to minimize risk of developing metastases.
Inflammatory gene variants have been associated with several diseases, including cancer, diabetes, vascular diseases, neurodegenerative diseases, arthritis, and others. Therefore, determining the population genetic composition of inflammation-related genes can be useful for the determination of general risk, prognostic and therapeutic strategies to prevent or cure specific diseases. We have aimed to identify polymorphism genotype frequencies in genes related to the inflammatory response in the Brazilian population, namely, IjBL -62AT, IjBL -262CT, tumor necrosis factors alpha (TNFa) -238GA, TNFa -308GA, lymphotoxin-alpha (LTa) + 80AC, LTa + 252AG, FAS -670AG, and FASL -844TC, considering the white, black, and Pardo ethnicities of the Sã o Paulo State. Our results suggest that the Brazilian population is under a miscegenation process at the current time, since some genotypes are not in the Hardy-Weinberg equilibrium. In addition, we conclude that the Pardo ethnicity is derived from a complex mixture of ethnicities, including the native Indian population.
ABSTRACT. The C677T and A1298C polymorphisms in methylenetetrahydrofolate reductase (MTHFR), which regulates the release of active folate in the body, may have reduced activity. Given that folate participates in important intracellular pathways, such as nucleotide synthesis and biomolecule methylation, it seems plausible that patients with head and neck squamous cell carcinoma (HNSCC) may respond differently to radiotherapy treatments, based on genetic polymor- phisms. Therefore, this study sought to understand the role of these polymorphisms in HNSCC patient radiotherapy response. Genotypes were detected by PCR-RFLP after extraction of DNA from peripheral blood lymphocytes. Survival curves were analyzed by the KaplanMeier model, and significant differences were analyzed by the Wilcoxon test. Response to radiotherapy in patients with laryngeal SCC was significantly associated with the MTHFR C677T polymorphism (P = 0.030). Indeed, the presence of at least one T allele decreases the mortality rate up to 3-fold. Therefore, we propose that MTHFR C677T may represent a putative biomarker for radiotherapy prognosis in laryngeal SCC patients.
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