These findings do not confirm a previously reported association between urinary bisphenol A levels and self-reported type 2 diabetes.

BackgroundMany susceptible loci for type 2 diabetes mellitus (T2DM) have recently been identified from Caucasians through genome wide association studies (GWAS). We aimed to determine the association of 11 known loci with T2DM and impaired glucose regulation (IGR), individually and in combination, in Chinese.Methods/Principal FindingsSubjects were enrolled in: (1) a case-control study including 1825 subjects with T2DM, 1487 with IGR and 2200 with normal glucose regulation; and (2) a prospective cohort with 734 non-diabetic subjects at baseline. The latter was followed up for 3.5 years, in which 67 subjects developed T2DM. Nineteen single nucleotide polymorphisms (SNPs) were selected to replicate in both studies. We found that CDKAL1 (rs7756992), SLC30A8 (rs13266634, rs2466293), CDKN2A/2B (rs10811661) and KCNQ1 (rs2237892) were associated with T2DM with odds ratio from 1.21 to 1.35. In the prospective study, the fourth quartile of risk scores based on the combined effects of the risk alleles had 3.05 folds (95% CI, 1.31–7.12) higher risk for incident T2DM as compared with the first quartile, after adjustment for age, gender, body mass index and diabetes family history. This combined effect was confirmed in the case-control study after the same adjustments. The addition of the risk scores to the model of clinical risk factors modestly improved discrimination for T2DM by 1.6% in the case-control study and 2.9% in the prospective study.Conclusions/SignificanceOur study provided further evidence for these GWAS derived SNPs as the genetic susceptible loci for T2DM in Chinese and extended this association to IGR.

Objective: As an important regulator of embryonic morphogenesis, homeodomain-containing gene 10 (HOXC10) has been found to promote progression of human cancers and its expression indicates poor survival outcome. However, very few studies are available on the role of HOXC10 in gastric carcinoma. Therefore, the aim of this study was to determine the role of HOXC10 in gastric cancer and the potential mechanism underlying its function for cancer biology. Methods: A primary gastric cancer mouse model was obtained via intra-gastric wall injection of gastric cancer cells and was used to evaluate the function of HOXC10 during gastric cancer progression in vivo. Immunohistochemistry was performed to visualize and measure HOXC10 protein expression in gastric cancer tissue. Cells were transfected with plasmids to increase the expression of HOXC10, and siRNA transfection was performed to suppress HOXC10 expression. Reverse transcription polymerase chain reaction (RT-PCR) and western blotting were utilized to measure mRNA and protein expression, respectively. Proliferation, migration, and invasion were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, wound healing assay, and matrigel invasion assay in vitro, respectively. Results: HOXC10 expression was significantly increased in gastric cancer tissues compared to matched normal tissues. HOXC10 up-regulation significantly increased tumor volumes in nude mice. Plasmid transfection significantly increased HOXC10 protein and mRNA expressions and effectively promoted cell proliferation. Moreover, HOXC10 up-regulation significantly promoted migration and invasion of gastric cancer cells. Mechanistic investigation showed that HOXC10 up-regulation significantly increased mRNA and protein expression of mitogen-activated protein kinase (MAPK) signaling related genes, including c-myc, c-jun and p53, while also modulating the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and P38 but not their total protein levels. Conclusions: This study demonstrated the tight link between HOXC10 and gastric cancer cell proliferation and metastasis via involvement of the MAPK pathway.

XB130 is a cytosolic adaptor protein involved in various physiological processes and oncogenesis of certain malignancies, but its role in the development of prostate cancer remains unclear. In current study, we examined XB130 expression in prostate cancer tissues and found that XB130 expression was remarkably increased in prostate cancer tissues and significantly correlated with increased prostate specific antigen (PSA), free PSA (f-PSA), prostatic acid phosphatase (PAP) and T classification. Patients with highly expressed XB130 had significantly decreased survival, which suggested XB130 as a possible prognostic indicator for prostate cancer. In vitro experiments showed that reduced XB130 expression restrained tumor growth both in vitro and in vivo. Furthermore, XB130 knockdown hindered transition of G1 to S phase in prostate cancer cell line DU145 and LNCap, which might contribute to the inhibition of cellular proliferation. Results from transwell assay demonstrated that downregulation of XB130 may attenuate invasion and metastasis of prostate cancer. Semiquantitative analysis of Western blot suggested that decreased XB130 expression was accompanied by diminished Akt signaling and EMT process. Thus, above observations suggest that XB130 may be a novel molecular marker and potent therapeutic target for prostate cancer.