Oncotarget

Research Papers:

Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype

Patricia Carrera-Lasfuentes, Angel Lanas, Luis Bujanda, Mark Strunk, Enrique Quintero, Santos Santolaria, Rafael Benito, Federico Sopeña, Elena Piazuelo, Concha Thomson, Angeles Pérez-Aisa, David Nicolás-Pérez, Elizabeth Hijona, Jesús Espinel, Rafael Campo, Marisa Manzano, Fernando Geijo, María Pellise, Manuel Zaballa, Ferrán González-Huix, Jorge Espinós, Llúcia Titó, Luis Barranco, Mauro D’Amato and María Asunción García-González _

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Oncotarget. 2017; 8:35848-35862. https://doi.org/10.18632/oncotarget.16261

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Abstract

Patricia Carrera-Lasfuentes1, Angel Lanas1,2,3,4, Luis Bujanda1,5, Mark Strunk1,6, Enrique Quintero7, Santos Santolaria8, Rafael Benito1,2,9, Federico Sopeña1,2,3, Elena Piazuelo1,2,6, Concha Thomson10, Angeles Pérez-Aisa11, David Nicolás-Pérez7, Elizabeth Hijona1,5, Jesús Espinel12, Rafael Campo13, Marisa Manzano14, Fernando Geijo15, María Pellise1,16, Manuel Zaballa17, Ferrán González-Huix18, Jorge Espinós19, Llúcia Titó20, Luis Barranco21, Mauro D’Amato22, María Asunción García-González1,2,6

1CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

2Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain

3Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

4Faculty of Medicine, Universidad de Zaragoza, Zaragoza, Spain

5Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), San Sebastián, Spain

6Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain

7Department of Gastroenterology, Hospital Universitario de Canarias, Instituto Universitario de Tecnologías Biomédicas (ITB), Centro de Investigación Biomédica de Canarias (CIBICAN), Tenerife, Spain

8Department of Gastroenterology, Hospital San Jorge, Huesca, Spain

9Faculty of Medicine and Department of Microbiology, Hospital Clínico Universitario, Zaragoza, Spain

10Department of Gastroenterology, Hospital Obispo Polanco, Teruel, Spain

11Department of Gastroenterology, Hospital del Sol, Marbella, Spain

12Department of Gastroenterology, Complejo Hospitalario, León, Spain

13Department of Gastroenterology, Hospital Parc Tauli, Sabadell, Spain

14Department of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain

15Department of Gastroenterology, Hospital Clínico Universitario, Salamanca, Spain

16Department of Gastroenterology, Hospital Clinic I Provincial, Institut d Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain

17Department of Gastroenterology, Hospital de Cruces, Barakaldo, Spain

18Department of Gastroenterology, Hospital Josep Trueta, Girona, Spain

19Department of Gastroenterology, Mutua de Tarrasa, Spain

20Department of Gastroenterology, Hospital de Mataró, Mataró, Spain

21Department of Gastroenterology, Hospital del Mar, Barcelona, Spain

22BioDonostia Health Research Institute, IKERBASQUE, Basque Foundation for Science, San Sebastián, Spain

Correspondence to:

María Asunción García-González, email: asgarcia@unizar.es

Keywords: gastric cancer, Helicobacter pylori, polymorphism, DNA repair

Received: November 17, 2016     Accepted: February 27, 2017     Published: March 16, 2017

ABSTRACT

Variations in DNA repair genes have been reported as key factors in gastric cancer (GC) susceptibility but results among studies are inconsistent. We aimed to assess the relevance of DNA repair gene polymorphisms and environmental factors to GC risk and phenotype in a Caucasian population in Spain. Genomic DNA from 603 patients with primary GC and 603 healthy controls was typed for 123 single nucleotide polymorphisms in DNA repair genes using the Illumina platform. Helicobacter pylori infection with CagA strains (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.55–2.54), tobacco smoking (OR: 1.77; 95% CI: 1.22–2.57), and family history of GC (OR: 2.87; 95% CI: 1.85–4.45) were identified as independent risk factors for GC. By contrast, the TP53 rs9894946A (OR: 0.73; 95% CI: 0.56–0.96), TP53 rs1042522C (OR: 0.76; 95% CI: 0.56–0.96), and BRIP1 rs4986764T (OR: 0.55; 95% CI: 0.38–0.78) variants were associated with lower GC risk. Significant associations with specific anatomopathological GC subtypes were also observed, most notably in the ERCC4 gene with the rs1799801C, rs2238463G, and rs3136038T variants being inversely associated with cardia GC risk. Moreover, the XRCC3 rs861528 allele A was significantly increased in the patient subgroup with diffuse GC (OR: 1.75; 95% CI: 1.30–2.37). Our data show that specific TP53, BRIP1, ERCC4, and XRCC3 polymorphisms are relevant in susceptibility to GC risk and specific subtypes in Caucasians.


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