title: Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and susceptibility to gastric adenocarcinoma in an Italian population.
abstract: Methylenetetrahydrofolate reductase (MTHFR) plays a central role in the metabolism of folate, which provides a methyl donor for DNA methylation and deoxynucleoside synthesis. We performed a case-control study to explore the relationship between two common MTHFR polymorphisms (C677T and A1298C), their combination and interaction with environmental exposures, on gastric adenocarcinoma susceptibility and progression in an Italian population. One hundred and two cases and 254 hospital controls, matched by age and gender, were enrolled. Individuals carrying the MTHFR 677T allele showed an increased risk of gastric cancer (odds ratio (OR) 1.62, 95% confidence interval (CI) 0.98-2.67), particularly among ever smokers (OR 2.10, 95% CI 1.07-5.33) and, among 677 TT individuals, those with a low intake of fruit and vegetables (OR 2.18, 95% CI 1.05-4.54). The strongest effect, however, was noted for the MTHFR 677 TT genotype among the diffuse gastric cancer histotype (OR 2.92, 95% CI 1.12-7.60). No association was detected for the effect of MTHFR A1298C polymorphism. Survival analysis did not show any association between each polymorphism on the overall survival, although when the analysis was restricted to the first year of follow-up after the surgical intervention an improved survival was noted among MTHFR 677 CC subjects compared with the T allele carriers (p value for log-rank test 0.02). In conclusion, MTHFR 677 (any T genotype) appears to modulate an individual's susceptibility to gastric cancer, particularly when combined with cigarette smoking and among those with a low intake of fruit and vegetables. Our results also suggest that an aberrant DNA methylation pattern, through impaired folate metabolism, might play a key role in gastric carcinogenesis. A possible survival effect of the MTHFR C677T genotype in gastric cancer patients deserves further investigations with larger sample sizes.
authors.affiliation: Institute of Hygiene, Rome, Italy. sboccia@rm.unicatt.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Boccia
authors.forename: Francesco
authors.initials: F
authors.lastname: Gianfagna
authors.forename: Roberto
authors.initials: R
authors.lastname: Persiani
authors.forename: Antonio
authors.initials: A
authors.lastname: La Greca
authors.forename: Dario
authors.initials: D
authors.lastname: Arzani
authors.forename: Stefano
authors.initials: S
authors.lastname: Rausei
authors.forename: Domenico
authors.initials: D
authors.lastname: D'ugo
authors.forename: Paolo
authors.initials: P
authors.lastname: Magistrelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Villari
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Van Duijn
authors.forename: Gualtiero
authors.initials: G
authors.lastname: Ricciardi
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D016022:Case-Control Studies; D019175:DNA Methylation; D004032:Diet / Q000009:adverse effects; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)