RESUMO
Squamous cell carcinoma of the oral cavity and oropharynx is the sixth most common type of cancer in the world. During tumorigenesis, gene promoter hypermethylation is considered an important mechanism of transcription silencing of tumor suppressor genes, such as DAPK, MGMT and RUNX3. These genes participate in signaling pathways related to apoptosis, DNA repair and proliferation whose loss of expression is possibly associated with cancer development and progression. In order to investigate associations between hypermethylation and clinicopathological and prognostic parameters, promoter methylation was evaluated in 72 HPV negative oral and oropharyngeal tumors using methylation-specific PCR. Hypermethylation frequencies found for DAPK, MGMT and RUNX3 were 38.88%, 19.44% and 1.38% respectively. Patients with MGMT hypermethylation had a better 2-year overall survival compared to patients without methylation. Being MGMT a repair gene for alkylating agents, it could be a biomarker of treatment response for patients who are candidates for cisplatin chemotherapy, predicting drug resistance. In view of the considerable levels of hypermethylation in cancer cells and, for MGMT, its prognostic relevance, DAPK and MGMT show potential as epigenetic markers, in a way that additional studies may test its viability and efficacy in clinical management.
RESUMO
Abstract Objectives: To contribute to a better understanding of the maternal genetic mechanisms that influence obstetric outcomes and that are involved in maternal and child health, this study aimed to evaluate the association between maternal genetic variants and the offspring birth weight by analyzing single-nucleotide polymorphisms (SNPs) in genes related to glucose homeostasis. Methods: Three polymorphisms were analyzed (GCK rs1799884, TCF7L2 rs7903146 and LEPR rs1137101) in 250 pregnant women who participated in a Brazilian prospective cohort study. Genotyping was performed by Real-Time Polymerase Chain Reaction (qPCR) using pre-designed TaqMan® SNP genotyping assays. Vitamin D dosage was performed by chemiluminescence. Variance, Pearson's chi-square test and multiple linear regression were used for the statistical analysis. Results: It was possible to verify a significant association between birth weight and maternal GCK rs1799884 when obstetric outcomes, clinical and anthropometric characteristics were taken into consideration. The children of homozygous women for the minor allele GCK rs1799884 presented lower birth weight (β = -335.25, 95% CI = -669.39; -1.17, p = 0.04). Furthermore, a direct link between a leptin receptor variant and gestational duration was found (p = 0.037). Conclusion: The variant GCK rs1799884 (mm) was associated with a reduction in newborn weight in the miscegenated Brazilian population.