[The relationship between methylenetetrahydrofolate reductase gene polymorphism and microsatellite instability in gastric cancer].
OBJECTIVE
To explore the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and microsatellite instability (MSI) in patients with gastric cancer.


METHODS
MTHFR gene C677T and A1298C polymorphism were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and MSI was examined with PCR.


RESULTS
MTHFR gene C677T and A1298C polymorphisms were analyzed on 122 gastric cancers and 110 normal controls The genotype frequencies of MTHFR 677CC, 677CT and 677TT were 47.5%, 39.3% and 13.1% on patients with gastric cancer, and 48.5%, 42.6%, 8.9% in the controls respectively. There was no significant difference of genotype frequency between the two groups (P > 0.05). The individuals with 677CT genotype, 677TT genotype and 677CT + TT genotype exhibited significantly reduced risk (OR = 0.38,95% CI: 0.15-0.98; OR = 0.26,95% CI: 0.03-2.18 and OR = 0.36,95% CI: 0.07-0.98) of developing gastric cardia cancer compared with those harboring the wild-type(677CC). The individuals with 677TT genotype having a 3.03-fold (95% CI: 1.07-8.65) increased risk of developing gastric corpus cancer. The genotype frequency of MTHFR 1298AA, 1298AC and 1298CC were 59.8%, 36.1% and 4.1% in gastric cancer patients, and 57.4%, 7.6%, 5.0% in the controls, respectively. The distribution of MTHFR A1298C genotype was not significantly different between gastric cancer and controls (P > 0.05). The individuals with 1298CC genotype had a reduced risk of developing gastric antrum cancer (OR = 0.41- fold, 95% CI: 0.03-2.18, 0.05-3.72) when comparing with those having 1298AA genotype. Patients with MSI+ gastric cancer had an increased frequency of the MTHFR 677TT genotype when comparing with those suffering from MSI- gastric cancer (P = 0.009) and with controlled subjects (P = 0.008). There was no significant association found between MTHFR A1298C polymorphism and MSI (P>0.05).


CONCLUSIONS
Polymorphism of MTHFR C677T was associated with increased risk on gastric corpus cancer and reduced risk on gastric cardia cancer. The polymorphism of MTHFR A1298C was associated with reduced risk for gastric antrum cancer while MSI pathway was possibly involved in the development of gastric cancer with MTHFR 677TT genotype.
Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Pei-ren
PR
Si
Dian-chun
DC
Fang
Hao
H
Zhang
Liu-qin
LQ
Yang
Yuan-hui
YH
Luo
Hua-yu
HY
Liao
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D053842:Microsatellite Instability; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000235:genetics*
D042965:Methylenetetrahydrofolate Reductase (NADPH2)