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Published data on the relationship between T309G polymorphism in the murine double minute 2 (MDM2) gene and susceptibility of digestive tract cancers (DTC) are inconclusive. Thus, the aim of this study is to determine whether MDM2 T309G polymorphism is associated with the risk of diverse DTC, including esophagus, stomach, liver, bile duct, pancreas, and colorectum cancers. Relevant studies were identified up to October 1, 2013. Crude odds ratio (OR) and 95% confidence interval (CI) were used as a measure of the strength of the association. The pooled result based on all studies showed that there was a statistically significant link between MDM2 T309G polymorphism and DTC susceptibility (T vs. G: OR = 0.82, 95%CI = 0.76-0.88). When stratified by race, significant associations were observed for all genetic models among Asians (especially in Chinese population), but not among Caucasians. Subgroup analyses according to tumor location indicated that the genetic variant was associated with esophageal (OR = 0.88, 95%CI = 0.81-0.96 for T vs. G), hepatocellular (OR = 0.69, 95%CI = 0.57-0.84 for T vs. G) and pancreatic cancer risk but not associated with cholangiocarcinoma or colorectum cancer susceptibility. Meanwhile, the G allele was also suggested to be associated with increased gastric cancer risk (OR = 0.68, 95%CI = 0.54-0.87 for TT + TG vs. GG for intestinal type of gastric cancer and OR = 0.18, 95%CI = 0.06-0.50 for TT vs. GG for Helicobacter pylori infection positive stomach cancer). Our study indicates that the MDM2 T309G polymorphism may be an ethnicity-dependent risk factor for DTC, especially for the upper gastrointestinal tract malignancies.

Background: Gastric cancer is frequently lethal despite aggressive multimodal therapies, and new treatment approaches are therefore needed. Retinoids are potential candidate drugs: they prevent cell differentiation, proliferation and malignant transformation in gastric cancer cell lines. They interact with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors, each with three subclasses, α, β and γ. At present, little is known about retinoid expression and influence on prognosis in gastric cancers. Patients and Methods: We retrospectively analyzed the expression of the subtypes RARa, RARβ, RARγ, RXRa, RXRβ, RXRγ by immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium tissues for whom clinical follow-up data were available and correlated the results with clinical characteristics. In addition, we quantified the expression of retinoid receptor mRNA using realtime PCR (RT-PCR) in another 6 gastric adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). Results: RARa, RARβ, RARγand RXRγ positively correlated with each other (p < 0.001) and demonstrated significantly lower levels in the carcinoma tissue sections (p < 0.01), with lower RARβ, RARγ and RXRa expression significantly related to advanced stages (p < =0.01). Tumors with poor histopathologic grade had lower levels of RARa and RARβ in different histological types of gastric carcinoma (p < 0.01). Patients whose tumors exhibited low levels of RARa expression had significantly lower overall survival compared with patients who had higher expression levels of this receptor (p < 0.001, HR=0.42, 95.0% CI 0.24-0.73), and patients undergoing ATRA treatment had significantly longer median survival times (p = 0.007, HR=0.41, 95.0% CI 0.21-0.80). Conclusions: Retinoic acid receptors are frequently expressed in epithelial gastric cancer with a decreased tendency of expression and RARa may be an indicator of a positive prognosis. This study provides a molecular basis for the therapeutic use of retinoids against gastric cancer.

OBJECTIVES Free portal pressure measurement is a reliable method for assessment of portal pressure in patients with cirrhosis. Intrahepatic circulatory time analysis of a sonographic contrast agent can assess liver fibrosis and its severity. The purposes of this pilot study were to assess the correlation between the intrahepatic circulatory time and free portal pressure and to assess whether intrahepatic circulatory time analysis can be used to predict portal venous pressure severity. METHODS The intrahepatic circulatory time and free portal pressure were measured in 31 patients with hepatitis B virus-related liver disease. Pearson correlation analysis was used to assess the correlation between the intrahepatic circulatory time and free portal pressure. RESULTS The hepatic vein-hepatic artery interval times were significantly shorter in the portal hypertension group than the non-portal hypertension group (mean ± SD, 8.26 ± 1.94 and 13.83 ± 1.17 seconds, respectively; P < .001). The portal vein-hepatic artery interval times were significantly longer in the portal hypertension group than the nonportal hypertension group (13.13 ± 2.25 and 7.25 ± 1.81 seconds; P < .001). Considering the whole patient population, there were statistically significant correlations between free portal pressure and the hepatic vein-hepatic artery interval time (r = -0.900; P < .001) and portal vein-hepatic artery interval time (r = 0.808; P < .001). In patients with portal hypertension, there was a statistically significant correlation between free portal pressure and the hepatic vein-hepatic artery interval time (r = -0.804; P = .009) and a weak correlation between free portal pressure and the portal vein-hepatic artery interval time (r = 0.506; P = .036). CONCLUSIONS Intrahepatic circulatory time measurement is correlated with free portal pressure and has the potential capability to evaluate portal pressure noninvasively in patients with hepatitis B virus-related liver disease.

Studies investigating the association between genetic polymorphism of aldehyde dehydrogenases-2 (ALDH-2) Glu487Lys and colorectal cancer (CRC) risk have reported conflicting results. Given this uncertainty, we carried out a critical analysis of published case-control studies to derive a more precise estimation of this relationship. Published literature from PubMed, EMBASE and China Knowledge Resource Integrated Database were retrieved, and the literature search was updated in June 2014. Eleven studies comprising 6965 subjects were selected (2300 cases and 4665 controls). Overall, our study showed no statistical significance for CRC risk associated with any of the genetic models of ALDH-2 Glu487Lys polymorphism. When studies were stratified for control source, a decreased risk of CRC for participants with Lys/Lys was observed in population based case-control studies [Lys/Lys vs. (Glu/Lys + Glu/Glu): odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.38–0.87]. Furthermore, we also confirmed the significant correlation between Glu487Lys polymorphism and the influence on the risk of rectal cancer in males [Glu/Glu vs. (Glu/Lys + Lys/Lys): OR = 1.52, 95%CI = 1.10–2.08]. The combined effects of the two gene polymorphisms [ALDH-2 and alcohol dehydrogenase 1B (ADH-1B)] were also studied. Compared with subjects having ALDH-2 Lys+ with ADH-1B His/His, ORs and 95%CIs for those with ALDH-2 Glu/Glu and ADH-1B His/His was 3.42(0.57–20.38). Similar trends were observed for the other two types of comparisons. Our study supports that ALDH-2 Glu487Lys polymorphism is associated with significant reduced risks of CRC in population-based samples, and of rectal cancer in males.