The Study On Leptin Receptor Gene Polymorphsims And Environmental Factors Interaction Associated With The Susceptibility Of Gastric Cancer

BackgroundGastric cancer (GC) is the top five mortality of malignant tumors. GC is one of the tumors which with the highest incidence and mortality in digestive system in China. GC occurrence is owing to various factors and processes, such as diet, smoking and drinking, carcinogen, genetic factors and etc. Genetic factors include the out of control of genes, DNA methylation and single nucleotide polomorphisms (SNPs). Recent years, multiple studies focus on the pathogenesis of GC. However, up to now, the etiology of GC is not well known. Previous researches indicate that genetic and environment factors play significant roles in the GC occurring process. Researches also have revealed multiple biomarkers, which related to the GC susceptibility, including Leptin receptor (LEPR) gene.LEPR protein belongs to the gp130 cytokine receptors family, it is firstly found that is expressed in the hypothalamus, and expressed in human gastric mucosa. LEPR gene is mapped to 1p31, include 20 exons, and play an important role in the regulation of body fat balance and energy metabolism. Additionally, the LEPR gene has become a research focus since its polymorphisms were discovered. A number of studies have shown that mutations in LEPR might associate with obesity and some clinical diseases. LEPR polymorphisms can affect nervous system and different kinds of gastrointestinal hormones through regulating the functions of the digestive system.Epidemiological studies have revealed that various SNPs might are the factors which play significant roles in the process of GC occurs, including LEPR polymorphisms. Researche had indicated that 7 nucleotide variants exist in LEPR gene. They are Lys109Arg(rs 1137100 locate at exon-2)?Gln223Arg(rs1137101 locate at exon-4)?Pro1019Pro?Ala976Asp?Ser343Ser?Ser492Thr and Lys656Asn. The former four mutation rate is higher, respectively is 79%,91%,85%,100%. Gln223Arg is most studied.Recently, evidence from experimental human with gastric cancer researches indicated tha the genotypes of Lys109Arg, Gln223Arg and Pro1019Pro is significantly associated with susceptibility of gastric cancer. Besides, multiple studies clarified that environmental factors might enhance the susceptibility of many diseases, including GC. In China, there were seldom researches related to the LEPR variants and GC risk, and the study on the the correlate of GC risk with gene-environment interaction was also poor.Therefore, we carried out this study to probe the correlation between LEPR SNPs (rs1137100 and rs1137101) and GC susceptibility in Chinese Han population. we performed a further study on the correlate of GC risk with gene-environment interaction.ObjectiveTo analyze the relationship between the leptin receptor (LEPR) gene polymorphisms (rs1137100 and rs 1137101) and gastric cancer (GC) susceptibility. Besides, explore the interactions between environmental factors and LEPR polymor-phisms(rs1137100 and rs1137101)in GC.MethodsPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to analyze the polymorphisms of rs1137100 and rs1137101 in 89 GC sufferers and 97 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to detecte the leptin levels in blood. What's more, Hardy-Weinberg equilibrium was used to distinguish the differences of the frequencies of genotypes. Gene-environment interaction was assessed by crossover analysis. The risk of GC was evaluated by Odds ratios (ORs) and 95% confidence intervals(95%CI).ResultsThe GC group had a higher BMI(Body Mass Index) and leptin level compared with contort group (P<0.05).Analysis of LEPR polymorphisms and GC risk showed that AA genotype and A allele of rsl 137100 were significantly decreased the GC risk (P=0.036, OR=0.259,95%CI=0.068-0.987; P=0.008, OR=0.493,95%CI=0.291-0.833). No obvious correlation have existed between rs1137101 AA and GA genotypes and the risk of GC. But, rs1137101 A allele might reduce the GC risk (P=0.006, OR=0.446, 95%CI=0.248-0.802). Gene-environment interaction analysis denominated that rs1137100 GG and GA genotypes and environmental factors (such as preserved food,smoking,family history of cancer)interaction increased the risk of GC, and the same to rs1137101 GG and GA genotypes. rs1137101 GG and GA genotypes and the above mentioned risk factors interaction also increased the risk of GC.ConclusionA allele of rs1137100 and A allele of rs 1137101 might decrease the GC risk, respectively. Interactions between environmental factors and the polymorphisms of LEPR gene locus(rs1137100 and rs1137101)were positive with GC risk.