title: Polymorphism of estrogen response element in TFF1 gene promoter is associated with an increased susceptibility to gastric cancer.
abstract: TFF1 is a cysteine-rich protein that forms a characteristic trefoil domain through disulfide bonds, which render it resistant to vigorous conditions and it involves in maintaining the integrity of the gastric mucosa. Decreased expression of TFF1 gene plays a role in the development of gastric cancer. We examined the association between the promoter polymorphisms of the TFF1 gene and the risk of development of gastric cancer, in a case-control study including 199 controls and 141 patients with gastric cancer. Assessment of single nucleotide polymorphisms in the promoter region of the TFF1 gene was performed by sequencing and polymerase chain reaction-based restriction fragment length polymorphism. We found a statistically significant increased risk of gastric cancer associated with -394 TT genotypes (OR=8.78, CI=2.85-27.05, p<0.001) and CT (OR=1.64, CI=1.04-2.60, p=0.033). This single nucleotide polymorphism occurs naturally in an estrogen response element. According to induction of the TFF1 gene by estrogen, it is possible that the substitution of C to T results in a decreased estrogen receptor binding affinity to the estrogen response element and in turn it decreases the expression of the TFF1 gene that may be involved in development of gastric cancer over a lifetime.
authors.affiliation: School of Medicine, Kazerun Branch, Islamic Azad University, Kazerun, Iran. mehdimoghani@yahoo.com
authors.forename: Mehdi
authors.initials: M
authors.lastname: Moghanibashi
authors.forename: Parisa
authors.initials: P
authors.lastname: Mohamadynejad
authors.forename: Maryam
authors.initials: M
authors.lastname: Rasekhi
authors.forename: Abbas
authors.initials: A
authors.lastname: Ghaderi
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mohammadianpanah
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004967:Estrogens / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D020218:Response Elements; D013274:Stomach Neoplasms / Q000235:genetics*; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D004967:Estrogens; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins