A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk.Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis.Results After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population.Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

The Association between miR-196a2 rs11614913 Polymorphism and Digestive System Cancer Risk: A Meta-Analysis of 34 Studies

Background: MicroRNAs (miRNAs) negatively regulate the gene expression and act as tumor suppressors or oncogenes in carcinogenesis. The association between single nucleotide polymorphism (SNP) in miR-196a2 rs11614913 and the susceptibility of digestive system cancers was inconsistent in previous studies. Methods: A standardized search of PubMed, Embase, and Cochrane library databases for publications on miR-196a2 rs11614913 polymorphism and digestive system cancer risk was performed. Then the genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association. Test of heterogeneity, sensitivity analysis and assessment of publication bias were conducted in the present meta-analysis by STATA software 12.0. Results: An updated meta-analysis based on 34 independent case-control studies consisting of 13,013 cases and 16,046 controls was performed to address this association. There was a remarkable association between miR-196a2 rs11614913 polymorphism and overall digestive system cancer risk, especially in Asian populations. Moreover, subgroup analysis revealed that variant C allele increased risk of colorectal carcinoma, gastric cancer and hepatocellular carcinoma (HCC), compared with wild T allele. Conclusions: There was a remarkable association between miR-196a2 rs11614913 polymorphism and overall digestive system cancer risk, especially in Asian populations.

ZiyuglycosideⅡinhibits the growth of digestive system cancer cells through multiple mechanisms

Digestive system cancers,including liver,gastric,colon,esophageal and pancreatic cancers,are the leading cause of cancers with high morbidity and mortality,and the question of their clinical treatment is still open.Previous studies have indicated that ZiyuglycosideⅡ(ZYGⅡ),the major bioactive ingredient extract from Sanguisorba officinalis L.,significantly inhibits the growth of various cancer cells.However,the selective anti-tumor effects of ZYGⅡagainst digestive system cancers are not systemically investigated.In this study,we reported the anti-cancer effect of ZYGⅡon esophageal cancer cells(OE21),cholangiocarcinoma cells(Hu CCT1),gastric cancer cells(BGC-823),liver cancer cells(Hep G2),human colonic cancer cells(HCT116),and pancreatic cancer cells(PANC-1).We also found that ZYGⅡinduced cell cycle arrest,oxidative stress and mitochondrial apoptosis.Network pharmacology analysis suggested that UBC,EGFR and IKBKG are predicted targets of ZYGⅡ.EGFR signaling was suggested as the critical pathway underlying the anti-cancer effects of ZYGⅡand both docking simulation and western blot analysis demonstrated that ZYGⅡwas a potential EGFR inhibitor.Furthermore,our results showed synergistic inhibitory effects of ZYGⅡand chemotherapy 5-FU on the growth of cancer cells.In summary,ZYGⅡare effective anti-tumor agents against digestive cancers.Further systemic evaluation of the anti-cancer activities in vitro and in vivo and characterization of underlying mechanism will promote the development of novel supplementary therapeutic strategies based on ZYGⅡfor the treatment of digestive system cancers.