[Single nucleotide polymorphisms in methylenetetrahydrofolate reductase gene and susceptibility to cancer of the gastric cardia in Chinese population].
OBJECTIVE
To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), a central enzyme in folate metabolism that affects DNA methylation and synthesis, and the risk of adenocarcinoma of the gastric cardia (AGC).


METHODS
Genomic DNA was isolated from the peripheral lymphocytes of 205 patients with AGC and 360 age-and-sex-matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR genes C6677T and A1298C and the relation between these genotypes and risk of AGC was analyzed.


RESULTS
The genotype frequency of MTHFR C677CC was 35.0% among the controls and was 20.5% among the AGC patients; the genotype frequency of 677CT was 47.8% among the controls and 50.7% among the AGC patients, and the genotype frequency of 677TT was 17.2% among the controls and 28.8% among the AGC patients % (chi(2) = 17.63, P = 0.0002). The individuals with 677CT genotype or 677TT genotype had a 1.76-fold [95% confidence interval (CI), 1.13 - 2.76] or 2.97-fold (95% CI, 1.75 - 5.05) increased risk of developing AGC compared with those who had 677CC genotype. The distribution of MTHFR A1298C genotype was not significantly different between the two groups (chi(2) = 0.08, P = 0.96). The value of odd ratio (OR) in the individuals with 677CT//1298AA genotype (95% CI, 1.48 approximately 6.48), and the value of OR in the individuals with 677CT/1298CC genotype was 17.00 (95% CI, 1.26 approximately infinity; P = 0.042).


CONCLUSIONS
Single nucleotide polymorphism in the MTHFR gene is a risk factor of carcinogenesis of AGC in the Chinese population. Although the MTHFR A1298C polymorphism was not associated with AGC, The risk of developing AGC in the individuals with MTHFR677CT/1298CC was 17 times higher than that in the individuals with MTHFR677CC/1298AA, thus showing that a joint effect exists between the MTHFR 677 and 1298 polymorphisms on the risk of AGC.
Department of Etiology & Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Xiaoping
X
Miao
Deyin
D
Xing
Wen
W
Tan
Wenfu
W
Lu
Dongxin
D
Lin
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002299:Cardia / Q000473:pathology*; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*
D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)