Evaluation of the relationship between dietary factors,CagA-positive Helicobacter pylori infection,and RUNX3 promoter hypermethylation in gastric cancer tissue

AIM:To evaluate the relationship among Helicobacter pylori(H.pylori) infection,CagA status,and dietary factors with RUNX3 promoter hypermethylation.METHODS:Gastric cancer tissue samples were collected from 184 South Korean patients.All patients were interviewed following a semi-quantitative food frequency questionnaire.The average frequencies of intake and portion sizes of 89 common food items were documented,and total intakes of calories,nutrients,vitamins,and minerals were calculated for each subject.DNA was extracted from gastric cancer tissue samples,and amplification of the HSP60 gene was performed to detect H.pylori infection.Nested polymerase chain reaction(PCR) was used to detect the presence of the CagA gene.RUNX3 gene expression was measured by reverse transcription-PCR,and RUNX3 methylation status was evaluated by methylation-specific PCR.The odds ratios(ORs) and 95%CI associated with RUNX3 promoter hypermethylation status were estimated for each of the food groups,lifestyle factors,and the interaction between dietary and lifestyle factors with CagA status of H.pylori infection.RESULTS:Overall,164 patients(89.1%) were positive for H.pylori DNA,with the CagA gene detected in 59(36%) of these H.pylori-positive samples.In all,106(57.6%) patients with gastric cancer demonstrated CpG island hypermethylation at the RUNX3 promoter.RUNX3 expression was undetectable in 52(43.7%) of the 119 gastric cancer tissues sampled.A high consumption of eggs may increase the risk of RUNX3 methylation in gastric cancer patients,having a mean OR of 2.15(range,1.14-4.08).A significantly increased OR of 4.28(range,1.19-15.49) was observed with a high consumption of nuts in patients with CagA-positive H.pylori infection.High intakes of carbohydrate,vitamin B1,and vitamin E may decrease the risk of RUNX3 methylation in gastric cancer tissue,particularly in CagA-or H.pylori-negative infection,with OR of 0.41(0.19-0.90),0.42(0.20-0.89),and 0.29(0.13-0.62),respectively.A high consumption of fruits may protect against RUNX3 methylation.CONCLUSION:These results suggest that the CagA status of H.pylori infection may be a modifier of dietary effects on RUNX3 methylation in gastric cancer tissue.

ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population

AIM:To evaluate the association between the geneticpolymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.METHODS:The study subjects were 477 age-and sex-matched case-control pairs.Genotyping was performed for 15 single nucleotide polymorphisms(SNPs)in ITGA1.The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models.Multiple testing corrections were carried out following methodology for controlling the false discovery rate.Gene-based association tests were performed using the versatile gene-based association study(VEGAS)method.RESULTS:In the codominant model,the ORs for SNPs rs2432143(1.517;95%CI:1.144-2.011)and rs2447867(1.258;95%CI:1.051-1.505)were statistically significant.In the dominant model,polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors,with ORs of 1.337(95%CI:1.029-1.737)and 1.412(95%CI:1.061-1.881),respectively.In the recessive model,only the rs2432143 polymorphism was significant(OR=1.559,95%CI:1.150-2.114).The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model(OR=0.602,95%CI:0.212-0.709,P=0.021)and the dominant model(OR=0.653,95%CI:0.483-0.884).The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test.In the dominant model,the A-T type of ITGA1 haplotype block 2 was a significant risk factor(OR=1.341,95%CI:1.034-1.741).SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and,thus,to the risk of developing gastric cancer.CONCLUSION:ITGA1 gene SNPs rs1862610,rs2432143,and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.

Dietary vitamin D intake and vitamin D related genetic polymorphisms are not associated with gastric cancer in a hospital-based case-control study in Korea

There have been few studies on the association between vitamin D levels and gastric cancer in Asian populations,but no studies have been performed on the interactions between vitamin D intake and polymorphisms in the vitamin D pathway.The effects of vitamin D intake,vitamin D related genetic polymorphisms,and their association with the incidence of gastric cancer were investigated in a hospital case-control study,including 715 pairs of newly diagnosed gastric cancer patients and controls matched for age and sex.Correlations between vitamin D intake and plasma vitamin D concentrations were also assessed in a subset of subjects.No statistically significant difference was observed in the dietary intake of vitamin D between the patients and controls,nor were there any evident associations between vitamin D intake and risk of gastric cancer in multivariate analyses.Vitamin D intake significantly correlated with the circulating 25-hydroxyvitamin D levels,but not with the active form of the vitamin,1,25-dihydroxyvitamin D.There were no statistically significant interactions between vitamin D intake,and VDR or TXNIP polymorphisms.This study suggests that dietary vitamin D intake is not associated with gastric cancer risk,and the genetic polymorphisms of vitamin D-related genes do not modulate the effect of vitamin D with respect to gastric carcinogenesis.