| Association between environmental factors,polymorphisms of IL-1,IL-4,IL-8,IL-10 genes and gastric cancerGastric cancer is one of the most common malignant tumors in human life,and about 800 thousand new cases of gastric cancer are added every year.About 750 thousand people die of gastric cancer each year.Gastric cancer in our country in 80 years ranked first in residents of the incidence of malignant tumor,the incidence rate decreased gradually in recent years,the incidence of malignant tumor is still ranked 2013 in China's second residents,the mortality of malignant tumor mortality third.There are no definite conclusions about the etiology of gastric cancer at home and abroad,but it is generally believed that its occurrence and development are the result of the combined effects of various factors.At present,the research results show that the incidence of gastric cancer is mainly related to the two factors of environment and heredity,including lifestyle,genetic factors,biological factors,mental and psychological factors,etc..With the further study of the etiology of gastric cancer,the study of genetic susceptibility has gradually been localized at the level of Single(SNP,Nucleotide,Polymorphisms).This research mainly focused on immune inflammatory cytokine related gene single nucleotide polymorphism,combined with environmental factors,selected IL-1RN,IL-1B,IL-4,IL-8 and IL-10 genes,by using frequency matched case-control study design,study of environmental factors,genetic factors and the interaction between the the incidence of gastric cancer,gastric cancer etiology data so that the residents of the area,for gastric cancer prevention and early diagnosis and early treatment to provide reference.Methods:1)this study adopts frequency matched case-control study design,from January 2013-2015 year in December,in the Inner Mongolia Autonomous Region people's hospital diagnosed 340 cases of gastric cancer patients as case group,choose the same period in our hospital clinic and medical examination center received health examination subjects as the control group,the case group matching according to the frequency of sex and age the final group,a total of 364 subjects in the control.The self-designed "crowd lifestyle and environmental risk factors questionnaire",through clinical and epidemiological experts considered the revised survey by a group of trained investigators conducted face-to-face survey.The survey included basic information about the patient(including family history and Helicobacter pylori infection),dietary habits,lifestyle,and mental status.Statistical analysis was performed using SPSS 17.0 software,through the statistical data on the percentage of description,using non conditional Logistic on the risk factors of gastric cancer in univariate and multivariate non conditional Logistic regression regression calculation,partial regression coefficient beta,odds ratio(Odds Ratio,OR)and 95%confidence intervals(95%Confidence,Interval,CI).2)using EDTA-Na2 anticoagulant tube collected peripheral venous blood 3ml,using the sequenom MassARRAY platform,using matrix assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF-MS)detection of immune inflammation related genes IL-1RN-9876G>A,IL-1RN-9739A/G,IL-1RN-9091A>C,IL-1B+3954C>T,IL-4-590,T,C C,IL-4-5168 T IL-4-5107 T>>C,A>IL-4-5576 G,IL-8-251T>A,IL-10-592A>C,IL-10-1082A>G gene polymorphism,analysis of allele frequency and genotype in the case group and the control group of the 11 loci frequency distribution,single factor and multi factor non conditional Logistic regression,to investigate the relationship between polymorphisms of candidate gene and susceptibility to gastric cancer.SHEsis software was used to analyze the linkage disequilibrium between 3 loci of IL-1RN,4 loci of IL-4 and 2 loci of IL-10,and to analyze the relationship between haplotype and the risk of gastric cancer.3)polymorphism to environmental risk factors investigation and gene analysis results as the basis,further analysis the existence of interactions between genes and gene associated with gastric cancer genes and environment,and the effect of interaction on susceptibility.Results The first part of the 1)non conditional Logistic regression analysis showed that the single factor,with a family history of cancer(OR=3.340,95%CI=2.262-4.930),H.pylori(OR=2.706,95%CI=1.979-3.698 infection),meat more(OR=1.519,95%CI=1.227-1.880),eat more pickled food(OR=1.998,95%CI=1.633-2.420),eating hard food(OR=1.492,95%CI=1.087-2.048),diet no rules(OR=1.445,95%CI=1.059-1.972),do not use the refrigerator(OR=1.792,95%CI=1.172-2.740),excessive alcohol consumption(OR=2.013,95%CI=1.227-1.880),drinking longer(OR=1.793,95%CI=1.325-2.426)is a risk factor for gastric cancer;the higher the BMI(OR=0.719,95%CI=0.552-0.936)and higher education level(OR=0.485,95%CI=0.384-0.612),OR=0.694(more vegetables that is,95%CI=0.544-0.885)of gastric cancer Protective factors2)non conditional Logistic regression analysis showed that,family history of cancer(OR=2.165,95%CI=1.125-4.168)and H.pylori infection(OR=2.286,95%CI=1.320-3.959),divorced/widowed(OR=10.517,95%CI= 1.194-92.608),pickled foods(OR=2.396,95%CI=,1.691-3.395)(OR=2.019,95%CI=1.391-2.932)excessive drinking,drinking longer(OR=2.094,95%CI=1.425-3.079)that is a risk factor for gastric cancer,and higher BMI(OR=0.606,95%CI=0.381-0.966),higher educational level(OR=0.450,95%CI=0.293-0.691),eating long(OR=0.685,95%CI=0.501-0.938)may be the protective factors of gastric cancer.The second part 1)of 11 SNPs loci of candidate genes for Hardy-Weinberg balance test,the results showed that in the control group,except IL-4-107(P<0.01),the genotype distribution of other loci with Hardy-Weinberg genetic equilibrium(P =0.945,0.214,0.999,0.768,0.096 0.248,0.357,0.998,0.995,0.821),this study showed that the gene frequency distribution better representative..2)there was no significant difference in the distribution between the two groups of IL-4-107,IL-4-168,I-L4-576,IL-8-251,IL-10-592,IL-10-1082 8 allele frequency(P>0.05),-9739,IL1RN and the difference of distribution of IL-1RN-9091 and IL-4-590 3 allele frequency between the two groups was statistically significant(P<0.05).3)case group compared with the control group genotype frequency,results showed no statistically significant difference between the distribution of IL-1RN-9876,IL-1RN-9091,IL-1B+3954,IL-4-107,IL-4-168,IL-4-576,IL-8-251,IL-10-592,IL-10-1082 9 locus genotype frequency between the two groups(P>0.05),-9739,IL-4-590 and IL-1RN,2 genes between the two groups in the frequency distribution of the difference was statistically significant(P<0.05).4)non conditional Logistic regression analysis showed that the single factor,compared with AG+GG and AA genotype IL-1RN-9739,can increase the risk of gastric cancer(OR=1.895,95%CI=1.293-2.777),compared with TC+CC and TT genotype IL-4-590,can increase the risk of gastric cancer(OR=1.931,95%CI=1.425-2.617).5)non conditional Logistic regression analysis showed that,AG+GG gene type IL1RN-9739 gene(OR=2.526,95%CI=1.316-4.848)and TC+CC gene type IL-4-590(OR=1.957,95%CI=1.187-3.226),IL-10 AC+CC OR=1.696 genotype-592,95%CI=1.018-2.824)can increase the risk of gastric cancer.6)IL-1RN-9876G>A,-9739A/G,-9091A>C three gene loci were found in linkage disequilibrium(D'<0.5,R2<0.8),the difference was statistically significant in the case group and the control group between AAC and GAA,GGC three haplotypes(P<0.05).IL-4 gene-590,C>T,-107,T>C,-168,T>C,-576,A>G four loci,no linkage disequilibrium relationship was found(D'<0.5,R2<0.8).The distributions of CCCA,CCTA,CTCG,TCCA and four haplotypes in the case group and the control group were statistically significant(P<0.05).IL-10-592A>C and-1082A>G G gene two loci,two loci were found in linkage disequilibrium(D'<0.5,R2<0.8),IL-10 gene haplotype in distribution between cases and controls showed no significant difference(P>0.05).The third part 1)by non conditional Logistic regression analysis of gene and gene interaction,will be influenced by the environment factors of gastric cancer as a confounding factor into the model after adjustment,the interaction between IL-4-590 TC+CC genotype and IL-10-592 AC+CC(OR=1.644 95%CI= 1.082-2.500).2)with IL-4-590 AG+GG and family history of cancer(OR=6.410,95%CI=3.704-11.111),H.pylori(OR=4.587,95%CI=2.915-7.246)infection,pickled food(OR=7.407,95%CI=4.292-12.821)and alcohol consumption(OR=7.092,95%CI=2.924-17.241),drinking(OR=10.000,95%CI=2.857-34.483)there is a positive interaction between several factors,effects of these factors has enlarged the role of risk the increased prevalence of gastric cancer in.Conclusions1)confirmed previous studies of environmental risk factors such as family history,H.pylori infection,bad eating habits and living habits are also the survey risk factor for gastric cancer,take the health education and health promotion and other means to change the habits of people is the key to prevention of environmental risk factors.2)the AG+GG genotype of the-9739 AC+CC gene,the TC+CC genotype of IL-4-590,and the IL-10-592 genotype of IL1RN can increase the risk of gastric cancer.3)there was no linkage disequilibrium between the three loci of IL-1RN gene,but the distributions of AAC,GAA,GCG in three cases were different between case group and control group.No linkage disequilibrium was found between the four loci of IL4 gene,but the distributions of CCCA,CCTA,CTCG,TCCA four haplotypes in the case group and the control group were different.No linkage disequilibrium was found between the two loci and the two loci of IL-10 gene,and there was no difference between the haplotypes in the cases and the controls.4)IL-4-590 TC+CC genotype interacts with IL-10-592 and AC+CC.5)IL-4-590 AG+GG has positive interaction with several factors,such as family history of cancer,H.,pylori infection,pickled food,alcohol consumption and drinking time. |
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