Helicobacter pylori genotype and polymorphisms in DNA repair enzymes : where do they correlate in gastric cancer?

Abstract

One of the mechanisms proposed by which H. pylori causes gastric cancer (GC) is through DNA damage due to chronic inflammation. Genomic integrity is guaranteed by repair enzymes such as APE-1, OGG-1, and PARP-1. Host genetic polymorphisms associated with the bacterial strain may influence the ability to repair the damage, contributing to the development of H. pylori-associated GC. The aim of this study was to determine the association of the polymorphisms APE-1 (T2197G), OGG-1 (C1245G), and PARP-1 (A40676G) with H. pylori-genotype in 109 patients with GC. Methods: Polymorphism was assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and H. pylori detection/genotyping by PCR. Results: In the intestinal subtype, PARP-1 wild-type was more frequent (P ¼ 0.001) in patients >50 years old. The repair enzymes genotypes analyzed in combination showed that the less pathogenic strains are associated with the APE-1 polymorphic allele and, unexpectedly, with PARP-1 wild-type, but this last one associated with APE-1 polymorphic allele or in older patients. Conclusions: Our results indicate the importance of H. pylori and APE-1 genotypes in the gastric carcinogenesis. Also, support the hypothesis of a decrease of PARP-1 wild-type activity in older individuals. Taken together these data may be an important clue to understand the role of low-virulence strains of H. pylori in gastric carcinogenesis and point the importance to analyze the polymorphisms as a group. J. Surg. Oncol. 2012;106:448–455.