Diabetes mellitus (DM) is inconsistently associated with thyroid cancer risk. The purpose of this study was to summarize findings from cohort studies regarding the strength of the association of DM with subsequent thyroid cancer risk. Electronic searches were performed in PubMed, EmBase, and the Cochrane Library to identify studies from inception to July 2016. Cohort studies reporting risk estimates with 95% confidence intervals (CIs) of thyroid cancer in DM and non-DM patients were included. A random-effects meta-analysis was performed to the risk of thyroid cancer in DM compared with non-DM participants. Sixteen cohort studies were included, with a total of 10,725,884 individuals. These studies reported a total of 8032 cases of thyroid cancer. Overall, DM was associated with an increased risk of thyroid cancer (relative risk [RR], 1.20; 95% CI, 1.09–1.33; P < .001). Further, there was no significant difference was found between DM and non-DM for the risk of thyroid cancer in men (RR, 1.14; 95% CI, 1.00–1.30; P = .057), while a significant correlation was found in a pooled analysis in women (RR, 1.11; 95% CI, 1.06–1.17; P < .001). Finally, subgroup analyses suggested that country and mean age might correlate with the relationship between DM and the risk of thyroid cancer. This study suggested that patients with DM have significantly increased risk of thyroid cancer compared nondiabetics. This positive association was prominent in women, and not significant in men. Further large-scale studies are required to verify the nature of the association, which should be evaluated in specific subpopulations.

Background: DOT1L, a methyltransferase of H3K79, was observed to be amplified and overexpressed in certain malignancies. This work was aimed at investigating the differences in DOT1L expression and its regulatory mechanism in gastric cancer and healthy samples.Methods: Immunohistochemistry was used to detect DOT1L levels in 101 cases of gastric cancer and marching adjacent normal tissues. DOT1L was inhibited by small interfering RNA (siRNA) and EPZ5676; a targeting drug. The ability of cells to proliferate were checked by CCK8 and clone formation assays, with flow cytometry for observing the cell cycle. qRT-PCR and western blot revealed the gene and protein profiles. Finally, the outcome of EPZ5676 administration was checked on a murine model.Results: The expression of DOT1L is significantly increased in gastric malignant tumors that is related to the degree of differentiation, lymph node metastasis and TNM staging. DOT1L serves as an independent marker for the prognosis of overall survival (OS) with high levels implying worse prognosis. In addition, DOT1L regulates CDK4 and CDK6 through H3K79me2, which leads to a change in the cell cycle at G1, thereby affecting the proliferation of tumors in vitro and in vivo.Conclusions: This is a first clinical demonstration of the applicability of DOT1L overexpression in gastric tumors. The work is suggestive of altered proliferation of cells by DOT1L via regulating cyclins and H3K79 methylation. This indicates the role of DOT1L in the prognosis and possible medical intervention of gastric cancer.

Background. Gastric cancer (GC) is a highly prevalent tumor type. The dysregulated expression of melanoma deficiency factor 2 (AIM2) has been observed in a range of tumor types. Herein, we explore the role of AIM2 in the regulation of GC progression. Methods. Gastric cancer cells BGC-823 and MGC-803 in logarithmic growth phase were divided into blank group (control), Control group (NC) and SH-AIM2 group, respectively. Control group and SH-AIM2 group were transfected with AIM2 NC and SH-AIM2, respectively. Nude mice were divided into blank group (control) and SH-AIM2 group, and the treatment methods were the same as above. Differential AIM2 expression in GC tissues was assessed via bioinformatics analyses, after which western blotting was used for analyzing the AIM2 levels in tumor and paracancerous tissues from five stomach cancer patients. In addition, qPCR and protein imprinting were used to assess AIM2 expression levels in GCcells, and AIM2 knockdown was conducted in MGC-803 and BGC-823cells, after which colony formation and EdU incorporation assay were utilized to assess cell proliferation. The oncogenic role of AIM2 was then assessed in mice and validated through immunohistochemical analyses. Results. GC tissues and cell lines exhibited marked AIM2 overexpression. AIM2 knockdown significantly impaired GC cell proliferation and migration, as confirmed through in vitro assays. In vivo experiments showed that both the increment ability and invasion and migration ability of AIM2 knockdown group were significantly lower than that of control and NC the change of AIM2 protein level would affect the change of MAPK pathway related protein level. Conclusions. AIM2 knockdown markedly suppresses the proliferation, migration, as well as invasion of GC cells via the inhibition of MAPK signaling, thereby slowing tumor progression. Overall, these results suggest that further analyses of AIM2 may offer clinically valuable insights that can aid in the treatment of human GC.