TCF7L2 rs7903146 polymorphism is associated with gastric cancer: A case-control study in the Venezuelan population.
OBJECTIVE
To explore the association between TCF7L2 rs12255372 and rs7903146 single nucleotide polymorphisms (SNPs) and gastric cancer risk in Venezuelan patients.


METHODS
We performed a case-control study including 122 paraffin-embedded archived intestinal-type gastric cancer samples and 129 biopsies obtained by superior endoscopy from chronic gastritis patients. Gastric cancer samples were classified according the degree of carcinoma differentiation. Genomic DNA was extracted from tissues, and the two SNPs of TCF7L2 gene (rs12255372 and rs7903146) were genotyped by polymerase chain reaction-restriction fragment length polymorphism reactions. Multiple regression analysis with adjustments for age and gender were performed and best-fitting models of inheritance were determined. Statistic powers were post-hoc calculated.


RESULTS
After adjusting for age and sex the TCF7L2 rs7903146 TT genotype was associated with gastric cancer risk under the recessive genetic model (OR = 3.11, 95%CI: 1.22-7.92, P = 0.017). We further investigated the distribution of rs12255372 and rs7903146 genotypes according gastric cancer stratified by degree of differentiation, and we observed that carriers of rs7903146 T allele (CT + TT vs CC) had a significantly increased risk of moderate/well differentiated gastric cancer (dominant model, OR = 2.55, 95%CI: 1.35-4.80, P = 0.004), whereas the rs7903146 TT genotype was associated with poorly differentiated gastric cancer in the recessive model (OR = 3.65, 95%CI: 1.25-10.62, P = 0.018). We did not find association between rs12255372 SNP and the susceptibility of developing gastric cancer.


CONCLUSIONS
TCF7L2 rs7903146 polymorphism is associated with gastric cancer risk in the Venezuelan population, and could be related to determine the degree of differentiation of tumor cells.
Keila Torres, Luis Labrador, Elvis Valderrama, Miguel Angel Chiurillo, Laboratorio de Genética Molecular "Dr. Jorge Yunis-Turbay", Decanato de Ciencias de la Salud, Universidad Centroccidental Lisandro Alvarado, Barquisimeto 3001, Venezuela.
Keila
K
Torres
Keila Torres, Luis Labrador, Elvis Valderrama, Miguel Angel Chiurillo, Laboratorio de Genética Molecular "Dr. Jorge Yunis-Turbay", Decanato de Ciencias de la Salud, Universidad Centroccidental Lisandro Alvarado, Barquisimeto 3001, Venezuela.
Luis
L
Labrador
Keila Torres, Luis Labrador, Elvis Valderrama, Miguel Angel Chiurillo, Laboratorio de Genética Molecular "Dr. Jorge Yunis-Turbay", Decanato de Ciencias de la Salud, Universidad Centroccidental Lisandro Alvarado, Barquisimeto 3001, Venezuela.
Elvis
E
Valderrama
Keila Torres, Luis Labrador, Elvis Valderrama, Miguel Angel Chiurillo, Laboratorio de Genética Molecular "Dr. Jorge Yunis-Turbay", Decanato de Ciencias de la Salud, Universidad Centroccidental Lisandro Alvarado, Barquisimeto 3001, Venezuela.
Miguel Angel
MA
Chiurillo
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D014687:Venezuela
C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein
Gastric cancer; Genetic susceptibility; Single nucleotide polymorphism; TCF7L2; Wnt/β-catenin pathway