Case Control Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2016; 22(28): 6520-6526
Published online Jul 28, 2016. doi: 10.3748/wjg.v22.i28.6520
TCF7L2 rs7903146 polymorphism is associated with gastric cancer: A case-control study in the Venezuelan population
Keila Torres, Luis Labrador, Elvis Valderrama, Miguel Angel Chiurillo
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 Torres, Postgrado en Ciencias Biológicas, Departamento de Biología Celular, Universidad Simón Bolívar, Caracas 1081-A, Venezuela
Elvis Valderrama, Departamento de Anatomía Patología, Hospital Antonio María Pineda-UCLA, Barquisimeto 3001, Venezuela
Miguel Angel Chiurillo, Departamento de Patologia Clínica, Universidade Estadual de Campinas, Campinas 13083, São Paulo, Brazil
Author contributions: Chiurillo MA and Valderrama E designed the research; Valderrama E collected material and clinical data from patients; Torres K and Labrador L performed the assays; Chiurillo MA, Torres K and Labrador L analyzed the data; Chiurillo MA wrote the paper.
Supported by CDCHT-UCLA grant001-CS-2013.
Institutional review board statement: The study protocol was approved by the Bioethics Committee of the School of Health Sciences, Universidad Centroccidental Lisandro Alvarado.
Informed consent statement: Informed consent was obtained from each patient.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Miguel Angel Chiurillo, MD, PhD, Departamento de Patologia Clínica, Universidade Estadual de Campinas, Campinas 13083, São Paulo, Brazil.
Telephone: +55-19-35217370 Fax: +55-19-35219434
Received: March 14, 2016
Peer-review started: March 15, 2016
First decision: May 12, 2016
Revised: May 25, 2016
Accepted: June 13, 2016
Article in press: June 13, 2016
Published online: July 28, 2016
Processing time: 130 Days and 4.5 Hours

To explore the association between TCF7L2 rs12255372 and rs7903146 single nucleotide polymorphisms (SNPs) and gastric cancer risk in Venezuelan patients.


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.


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.


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.

Keywords: Gastric cancer, Wnt/β-catenin pathway, TCF7L2, Single nucleotide polymorphism, Genetic susceptibility

Core tip: TCF7L2 transcription factor plays an important role in transcriptional activation induced by the Wnt/β-catenin pathway, which is reported to be associated with human carcinogenesis and it is found activated in 30%-50% of gastric cancers. TCF7L2 polymorphisms rs12255372 and rs7903146 are associated with a significant risk of type 2 diabetes and in the development of several types of cancer. This is the first report of association of these TCF7L2 variants with the risk of gastric cancer. We conducted a case-control study including samples of Venezuelan patients in which the rs7903146 T allele was found associated with the risk of gastric cancer, suggesting its use as potential diagnosis biomarker in patients with this malignance.