Diet-Derived Circulating Antioxidants and Risk of Digestive System Tumors: A Mendelian Randomization Study.

Previous observational case-control studies have shown significant controversy over the impact of dietary intake-related circulating antioxidants on the risk of digestive system tumors. We conducted a two-sample Mendelian randomized (MR) analysis to determine whether there was a significant causal relationship between increased levels of circulating antioxidants and digestive system tumors. Our circulating antioxidants (vitamin C, carotenoids, vitamin A, and vitamin E) were derived from absolute circulating antioxidants and circulating antioxidant metabolites, and their corresponding instrumental variables were screened from published studies. The digestive system tumors we studied included colorectal, gastric, pancreatic, liver, and esophageal cancer, and the corresponding summary GAWS (genome-wide association study) data were obtained from the UK Biobank database. We first evaluated the causal relationship between each tumor and circulating antioxidants and then used meta-analysis to summarize the results of MR analysis of different tumors. No significant associations were noted for genetically predicted circulating antioxidants and higher risk of digestive system tumors in our study. The pooled ORs (odds ratio) are 0.72 (95% CI: 0.46-1.11; ß-carotene), 0.93 (95% CI: 0.81-1.08; lycopene), 2.12 (95% CI: 0.31-14.66; retinol), and 0.99 (95% CI: 0.96-1.02; ascorbate) for absolute circulating antioxidants; for circulating antioxidant metabolites, the pooled ORs for digestive system tumors risk per unit increase of antioxidants were 1.29 (95% CI: 0.39-4.28; α-tocopherol), 1.72 (95% CI: 0.85-3.49; γ-tocopherol), 1.05 (95% CI: 0.96-1.14; retinol), and 1.21 (95% CI: 0.97-1.51; ascorbate), respectively. Our study suggested that increased levels of dietary-derived circulating antioxidants did not reduce the risk of digestive system tumors.

Comparable long-term survival of patients with colorectal or gastric gastrointestinal stromal tumors treated with endoscopic vs. surgical resection.

BACKGROUND AND AIMS: With the development of endoscopic technology, endoscopic treatment has been widely used in Gastrointestinal stromal tumors (GISTs). However, population-based studies comparing the long-term results of patients who received endoscopic treatment vs. Surgery are lacking. We used the Surveillance, Epidemiology, and End Results (SEER) database to analyze the long-term survival of colorectal or gastric GISTs who underwent primary tumor resection (endoscopic therapy or surgery) in the USA. METHODS: Patients with colorectal or gastric GISTs were selected from the SEER database between 2010 and 2015. Kaplan-Meier analyses and log-rank tests were used to evaluate the difference in the long-term survival between the endoscopic therapy group and the surgery group. We examined the association between different treatments and survival after using the multivariate cox proportional hazards model to adjust the relevant covariates. Besides, we used Propensity score matching (PSM) to overcome the different distributions of covariates between the two groups and then further compare the survival difference. RESULTS: In total, 2355 patients were enrolled in our study, of which 1999 (84.9%) received surgical treatment and 356 (15.1%) received endoscopic treatment. There was no significant difference in overall survival (OS) between the two groups before PSM. The median OS (73.5 months vs. 72.2 months) and 5-year OS rate (85.7% vs. 81.5%) of endoscopic therapy were similar to surgical patients (P = 0.34). The median Cancer-specific survival (CSS) and 5-year CSS rate in the endoscopic treatment group were higher than the surgical group before PSM, with 81.3 months, 97.1% versus 78.8 months, 92.7% (P = 0.011). After adjusting for other clinical factors and PSM, the long-term OS and CSS did not significantly differ between those treated surgically and treated endoscopically. CONCLUSION: Based on the American population, we preliminarily found that the long-term OS and CSS did not differ between patients undergoing endoscopic therapy and surgery.

Generation of mice with hepatocyte-specific conditional deletion of sphingosine kinase 1.

SphK1 gene has different roles in various types of cells in liver diseases, but most studies are based on global knockout mice, which hampers the study on the cellular and molecular mechanisms of SphK1. In order to further study the role of SphK1 in liver, SphK1 conditional knockout mice were constructed. A liver-specific SphK1 gene knockout mouse model was constructed by the Cre/Loxp recombinant enzyme system. PCR technologies and western blotting were used to identified the elimination of SphK1 gene in hepatocytes. SphK1flox/flox mice were used as a control group to verify the effectiveness of SphK1 liver-specific knockout mice from the profile, pathology, and serology of mice. The ablation of SphK1 in hepatic parenchymal cells was demonstrated by fluorescent in situ hybridization and the contents of S1P and Sph were measured by ELISA kit. The genotypes of liver in SphK1 conditional knockout mice were different from that of other organs. The mRNA and protein levels of SphK1 in liver tissue of SphK1 conditional knockout mice were almost depleted by compared with SphK1flox/flox mice. Physiology and pathology showed no significant difference between SphK1 liver conditional knockout mice and SphK1flox/flox mice. Additionally, SphK1 was eliminated in hepatocytes, leading to the reduce of S1P content in hepatocytes and liver tissues and the increase of Sph content in hepatocytes. The model of SphK1 gene liver conditional knockout mice was successfully constructed, providing a tool for the study of the roles of SphK1 in hepatocyte and liver diseases.