Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-7-21
pubmed:abstractText
Thymidylate synthase (TS) catalyzes the 5,10-methylene-tetrahydrofolate-mediated conversion of deoxyuridine monophosphate to deoxythymydine monophosphate, a nucleotide required for DNA synthesis and repair. The impaired TS expression has been shown to be related to 28 bp tandem repeats and a G-->C SNP in the 5'-UTR of TS. Folate deficiency has been demonstrated to play a role in gastroesophageal carcinogenesis. This case-control study was to examine the hypothesis that the TS polymorphisms, alone or in combination with serum folate status, may confer susceptibility of the hosts to gastroesophageal cancer. We analyzed TS genotype and serum folate concentration in 324 patients with esophageal squamous cell carcinoma (ESCC), 231 patients with gastric cardia adenocarcinoma (GCA) and 492 controls. It was found that compared with the normal expression TS genotype, the low expression TS genotype alone was significantly associated with increased risk of ESCC [adjusted odds ratio (OR) 1.47; 95% confidence interval (CI) 1.03-2.10] but not GCA (OR=0.98, 95% CI=0.68-1.40). More importantly, a significant interaction between the TS polymorphisms and serum folate status in risk of ESCC and GCA was observed. Among subjects with low serum folate concentration (<3 ng/ml), the ORs of ESCC and GCA for the low expression genotype were 22.63 (95% CI=10.44-49.05) and 4.08 (95% CI=1.94-8.59), which were greater than respective 9.97 (95% CI=5.67-17.53) and 1.88 (95% CI=1.18-3.24) for the normal expression genotype (P=0.002 and 0.029). These results suggest an important role for folate deficiency and impaired TS activity in the etiology of ESCC and GCA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1430-5
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15817609-Adult, pubmed-meshheading:15817609-Aged, pubmed-meshheading:15817609-Base Sequence, pubmed-meshheading:15817609-China, pubmed-meshheading:15817609-DNA Primers, pubmed-meshheading:15817609-DNA Repair, pubmed-meshheading:15817609-DNA Replication, pubmed-meshheading:15817609-Esophageal Neoplasms, pubmed-meshheading:15817609-Female, pubmed-meshheading:15817609-Folic Acid, pubmed-meshheading:15817609-Folic Acid Deficiency, pubmed-meshheading:15817609-Genotype, pubmed-meshheading:15817609-Humans, pubmed-meshheading:15817609-Male, pubmed-meshheading:15817609-Middle Aged, pubmed-meshheading:15817609-Polymerase Chain Reaction, pubmed-meshheading:15817609-Polymorphism, Single Nucleotide, pubmed-meshheading:15817609-Promoter Regions, Genetic, pubmed-meshheading:15817609-Reference Values, pubmed-meshheading:15817609-Risk Factors, pubmed-meshheading:15817609-Smoking, pubmed-meshheading:15817609-Stomach Neoplasms, pubmed-meshheading:15817609-Thymidylate Synthase
pubmed:year
2005
pubmed:articleTitle
Significant increase in risk of gastroesophageal cancer is associated with interaction between promoter polymorphisms in thymidylate synthase and serum folate status.
pubmed:affiliation
Department of Etiology and Carcinogenesis, Cancer Institute and Department of Epidemiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't