Associação entre polimorfismos em genes de enzimas de reparo do DNA e a progressão do câncer gástrico

Abstract

Gastric lesions (LG) extends from normal mucosa infected with Helicobacter pylori (H. pylori) and can progress to gastric cancer (GC) using a multi-step process. The H. pylori infection can cause different inflammatory responses and may result in accumulation of reactive oxygen species (ROS), whose instability causes oxidative DNA damage. The genomic integrity is guaranteed by major repair enzymes as XRCC-1 and MLH1. However, polymorphisms in these genes may influence the ability to repair and individual susceptibility of the host associated with the development of gastric cancer. Thus, this study aimed to investigate the association between polymorphisms of XRCC-1 G28152A and MLH1 -93 G>A repair enzymes, the LG and its progression to the CG. This study was obtained DNA from 369 patients, 152 CG and 217 with premalignant LG (LG), collected in four hospitals in Fortaleza-CE. The identification of the polymorphism was performed by PCR-RFLP. In 99% of cases it was possible to determine the genotypes. In this study it was found that the polymorphic homozygote genotype XRCC-1 G28152A, gave risk for the development of GC. On the other hand, stratified analyzes comparing GCI with other lesions showed that carriers the homozygous genotype polymorphic XRCC-1 28152AA were associated with protection for the active chronic gastritis and polymorphic allele XRCC-1 (A), a decrease for incidence of tumors in the region not cardia. Additionally when the metaplasia was compared to histological subtypes of CG was observed a protection for the development of the intestinal subtype associated with patients polymorphic homozygous genotype of MLH1 (AA). The data showed that polymorphisms in repair enzymes can interfere with the healing process efficiency, but differ when the modified profile analysis. Our findings contribute to the future establishment of a genotypic profile involved in the progression of CG.