[Correlations between serine hydroxymethyltransferase1 C1420T polymorphisms and susceptibilities to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma].
OBJECTIVE
Serine hydroxymethyltransferase (SHMT), a key enzyme in the folate metabolism, affects gene methylation and DNA synthesis through providing one-carbon units for purine, thymidylate, and methionine. It is closely related to the development and progression of tumors. This study was to investigate the correlations between SHMT1 C1420T single nucleotide polymorphisms (SNP) and susceptibilities to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA).


METHODS
SHMT1 C1420T SNP was genotyped by polymerase chain reaction-confronting two-pair primers (PCR-CTPP) analysis in 584 ESCC patients, 467 GCA patients, and 540 healthy controls. The correlations between SHMT1 C1420T SNP polymorphisms and susceptibilities to ESCC and GCA were analyzed with Logistic regression model.


RESULTS
Family history of upper gastrointestinal cancer (UGIC) significantly enhanced the risk of developing ESCC and GCA [the age, gender, smoking status, and family history of UGIC adjusted odds ratio (OR)=2.89, 95% confident interval (CI)=2.23-3.73; OR =1.68, 95% CI=1.28-2.23]. The frequency of 1420C/T genotype was significantly lower in ESCC and GCA patients than in healthy controls (12.0% vs. 16.5%, P<0.05; 10.9% vs. 16.5%, P<0.01). Compared with C/C genotype, C/T genotype significantly reduced susceptibilities to ESCC and GCA, with adjusted OR of 0.70 (95% CI=0.50-0.98) for ESCC and 0.55 (95% CI=0.38-0.81) for GCA. Stratification analysis showed that C/T genotype significantly reduced susceptibilities to ESCC and GCA among non-smokers, with adjusted OR of 0.54 (95% CI=0.33-0.90) for ESCC and 0.56 (95% CI=0.33-0.95) for GCA. In addition, C/T genotype significantly reduced susceptibility to GCA among individuals with or without UGIC history, with adjusted OR of 0.46 (95%CI=0.24-0.90) and 0.62 (95% CI=0.38-0.99) respectively, and reduced susceptibility to ESCC only among individuals with UGIC history, with adjusted OR of 0.51 (95% CI=0.29-0.89).


CONCLUSIONS
SHMT1 1420C/T genotype could significantly reduce susceptibilities to ESCC and GCA among individuals from high risk areas in Hebei Province of China.
Laboratory of Molecular Biology, Hebei Provincial Cancer Institute/The Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei 050011, P. R. China.
Yi-Min
YM
Wang
Wei
W
Guo
Xiu-Feng
XF
Zhang
Yan
Y
Li
Na
N
Wang
Hui
H
Ge
Li-Zhen
LZ
Wei
Deng-Gui
DG
Wen
Jian-Hui
JH
Zhang
D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012907:Smoking; D013274:Stomach Neoplasms / Q000235:genetics*
D012696:Glycine Hydroxymethyltransferase