DNA methyltransferase expression is associated with cell proliferation in salivary mucoepidermoid carcinoma.

OBJECTIVES: The present study investigated the correlation between the expression of DNA methyltransferase (DNMT)1, DNMT3A, and DNMT3B and the proliferation of mucoepidermoid carcinomas (MECs) using the molecular markers Ki-67 and cyclin D1. This study also demonstrates the effects of 5-aza-2-deoxycytidine (5AC) on the MEC tumor cell lines in relation to DNMT1 and DNMT3A expression, and cell-cycle arrest. MATERIALS AND METHODS: The immunohistochemistry of DNMT1, DNMT3A, DNMT3B, Ki-67, and cyclin D1 was analyzed in 40 samples of MEC and 15 samples of healthy minor salivary glands. The effects of 5AC on DNMT1 and DNMT3B expression in MEC cell lines were analyzed by Western blot, and the effects of 5AC on the cell cycle were analyzed using flow cytometry. RESULTS: The expression of DNMT1 and DNMT3B was more intense in MECs than in healthy salivary glands. A strong correlation was found between the expression of the DNMTs and the proliferation markers. This correlation was validated In Vitro, where treatment with 5AC reduced the expression of the DNMTs and the percentage of cells at the G2/M phase of the cell cycle. CONCLUSION: The expression of DNMT1, DNMT3A, DNMT3B is correlated significantly with the expression of Ki-67 and cyclin D1. The treatment with 5AC reduces DNMT expression and decreases the percentage of cells at the G2/M phase of the cell cycle, while increasing the cells at the G0/G1 phase.

Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers.

BACKGROUND: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. METHODS: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects. RESULTS: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 × 10-9). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk. CONCLUSIONS: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci.

HNdb: an integrated database of gene and protein information on head and neck squamous cell carcinoma.

The total amount of scientific literature has grown rapidly in recent years. Specifically, there are several million citations in the field of cancer. This makes it difficult, if not impossible, to manually retrieve relevant information on the mechanisms that govern tumor behavior or the neoplastic process. Furthermore, cancer is a complex disease or, more accurately, a set of diseases. The heterogeneity that permeates many tumors is particularly evident in head and neck (HN) cancer, one of the most common types of cancer worldwide. In this study, we present HNdb, a free database that aims to provide a unified and comprehensive resource of information on genes and proteins involved in HN squamous cell carcinoma, covering data on genomics, transcriptomics, proteomics, literature citations and also cross-references of external databases. Different literature searches of MEDLINE abstracts were performed using specific Medical Subject Headings (MeSH terms) for oral, oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinomas. A curated gene-to-publication assignment yielded a total of 1370 genes related to HN cancer. The diversity of results allowed identifying novel and mostly unexplored gene associations, revealing,for example, that processes linked to response to steroid hormone stimulus are significantly enriched in genes related to HN carcinomas. Thus, our database expands the possibilities for gene networks investigation, providing potential hypothesis to be tested. Database URL:http://www.gencapo.famerp.br/hndb.