| ?Objective?To explore the envoronmental risk factors of gastric cancer in Xianyou County;To investigate the relationship between genetic variants in mi RNA binding Sites of COPS2,CTSF,NT5 E,TERF1 and mi RNA with gastric cancer risk;Establish the best interaction model of gene-gene and gene-envoronmental and further analyze the interaction effects with gastric cancer.?Methods?1.Xianyou county in fujian province as the research site,collected 622 cases of gastric cancer which were confirmed by pathology in Xianyou Hospital of Fujian from March 2013 to November 2016.The high,medium and low incidence of gastric cancer in villages and towns were divided according to the standardized mortality rate of gastric cancer,and then took the village as a unit to select the healthy population randomly.1:1matched case-control investigation was based on population according to the age(ąthree years old),gender and residence.Take the face to face questionnaire survey methods and laboratory examination acquire the informationthe of general condition,lifestyle,diet habit,Helicobacter pylori infection,medical history,psychological factors and so on.Univariate and multivariate conditional logistic regression were used to identify the risk factors of gastric cancer and to estimate the odd ratios(ORs)and 95% confidence intervals(95%CIs).Random forest,classification trees model,crossover analysis method and Excel form radacted by Andersson were used to analyze the interaction effects.2.Genetic variants in miRNA binding Sites of COPS2,CTSF,NT5 E,TERF1 and miRNA were selected by bioinformatics software.Molecular epidemiology method was used in this study.5ml blood was collected from the objects of study and further extractedthe genomic DNA.The genotypes of polymorphisms were determined by Sequenom platform.Conditional logistic regression were used to analyze the relationship between gene polymorphism and gastric cancer,cardia cancer and non cardia cancer.3.GMDR software was used to establish the best interaction model of gene-gene and gene-envoronmental which the envoronmental factors and polymorphism locis have statistical significance.Logistic regression,crossover analysis method and Excel form radacted by Andersson were used to find the correlation between the best interaction model with the different parts of the gastric cancer.estimate the odd ratios(ORs)and 95%confidence intervals(95%CIs).?Results?1.Univariate conditional logistic regression analyse showed that:After controlling and considering other confounding factors,low degree of culture,BMI<18.5,use of pesticides,smoking,eating too fast,eating hard diet,irregular meals,high salt diet,often work immediately after a meal,eating spickles,HP infection,stomach disease history,family history of cancer,type A personality,often have trouble,get angry easily could increase the risk of gastric cancer in Xianyou county(P<0.05;and high economic income,use the refrigerator,BMI?25,drinking tea,often eat beef and mutton,eggs,fish and shrimp,dairy products,bean products,fruit,vegetables,edible fungus,garlic and Onions were the protect factors(P<0.05).2.Multivariate conditional logistic regression analyse showed that:smoking(OR=2.37,95%CI:1.29,4.35),the use of pesticides(OR=1.89,95%CI:1.14,3.14),eating hard diet(OR=5.97,95%CI:3.54,10.09),eating spickles(OR=2.05,95%CI:1.49,2.81),stomach disease history(OR=10.13,95%CI:3.77,27.22),family history of cancer(OR=9.17,95%CI:3.42,24.61)were the risk factors(P<0.05);and tea drinking(OR=0.54,95%CI:0.29,1,00),often eat beef and mutton(OR=0.56,95%CI:0.39,0.70),often eat vegetables(OR=0.52,95%CI:0.39,0.70)were the protect factors(P<0.05).3.The results of combined effect and interaction analysis of envoronmental risk factors indicated that hard food exerted the main effect in the development of gastric cancer(MDG = 59.16).Pickled vegetables intake and hard food diet,pickled vegetables intake and drinking tea,tea drinking and exposure to pesticides had combined effect.Thepositive interaction on multiplicative scale beteween pickled vegetables intake and hard food diet was observed,the positive interaction on additive scale beteween pickled vegetables intake and hard food diet,pickled vegetables intake and tea drinking were observed.4.The results of the relationship between genetic variants in miRNA binding sites of COPS2,CTSF,NT5 E,TERF1and miRNA with gastric cancer risk indicated that:The AG genotype and its dominant model(AG+GG)of rs4576 in 3'UTR of CTSF were associated with increased gastric risk,ORs were 1.51(95%CI:1.16,1.98)and 1.48(95%CI:1.14,1.92),Further stratified analysed showed that AG genotype and its dominant model(AG+GG)of rs4576 could also increased non cardia cancer risk(P<0.05);The CT genotype and its dominant model(CT+TT)of SNP rs6913634 in 3'UTR of NT5 E was associated with increased gastric risk,ORs were 1.63(95%CI:1.08,2.44)and 1.62(95%CI:1.09,2.40),Further stratified analysed showed that CT genotype and its dominant model(CT+TT)of rs6913634 could also increased cardia cancer risk(P<0.05).The AA genotype and recessive model of SNP rs2222722 in miR-20 a which binding with NT5 E increased cardia cancer risk OR was 1.80(95% CI:1.00,3.25).5.The results of interaction of gene-gene and gene-envoronmental showed that: in the dominant model of rs4576,the higher risk of gastric cancer was showed in individual who carried G allele and hard food diet(OR=5.75)and positive additive interaction was showed between the two factors,the higher risk of gastric cancer was also showed in individual who carried G allele and pickled vegetables intake(OR=4.44);in the recessive model of rs4576,the higher risk of gastric cancer was showed in individual who carried GG genotype and hard food diet(OR=4.42),the higher risk of gastric cancer was also showed in individual who carried GG genotype allele and pickled vegetables intake(OR=3.28).?Conclusion?1.A lot of pickles intaking under the condition of eating hard food or not drinking tea was associated with a high incidence of gastric cancer in Xianyou county.The interactions between environmental factors increased the influence on gastric cancer,comprehensive measures need to be taken on gastric cancer control.2.Smoking,the use of pesticides,eating pickles,eating hard diet,stomach disease,history,family history of cancer were the risk factors in Xianyou cuonty;and tea drinking,often eat beef and mutton,often eat vegetables were the protect factors.Corresponding measures should be taken to guide local people to develop good living habits and eating habits in order to reduce its incidence.3.The study was first discovered that the heterozygous mutation of CTSF 3'UTR rs4576 polymorphisms increases the risk of local people suffering from gastric cancer and non cardia cancer;The heterozygous mutation of NT5 E 3'UTR rs6913634 polymorphisms increases the risk of local people suffering from gastric cancer and cardia cancer;MiR-30 a which combined with the NT5 E,homozygous mutation of rs2222722 polymorphism increased the risk of local population suffering from cardia cancer;The positive interaction on additive scale beteween the dominant model of CTSF 3'UTR rs4576 polymorphisms and hard food so that can guide the local population who carrying adverse genotype of CTSF gene rs4576 to develop good eating habits,eat less hard food,thereby reducing the risk of gastric cancer. |
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