Association of the polymorphism in DNA repair enzymes and E-Cadherin gene with gastric carcinoma risk in population from Brazil

Abstract

SNPs have been associated with gastric cancer susceptibility. Thus, we evaluated the influence of SNPs in DNA repair genes APE1 2197(T>G) and MLH1 -93(G>A), as well as in CDH1 at positions -160 (C>A) and -347 (G>GA) in gastric cancer risk. Analyses were performed on 264 GC patients and 391 healthy controls matched by age and sex from two regions in Brazil, Ceará and Pará. In the general analysis, a protective was found for the GGA of the CDH1-347 (G>GA). Considering the GC subtypes, the polymorphic allele of both CDH1 SNPs was associated with protection to intestinal subtype. In this subtype, the MLH1 (G>A) allele A was associated with risk, contrast with protection to diffuse subtype. In females, a risk was associated with AA genotype of MLH1 (G>A) and a protection with APE1 (T>G) and CDH1 -347 (G>GA) polymorphic alleles. Considering H. pylori , the APE1 (T>G) G allele was associated with low virulence strains, while MLH1 (G>A) GA genotype was associated with more virulence strains. The MLH1 (G>A) A allele in the intestinal subtype was associated with more virulence strains. Considering the two regions studied, we observed that the associations found regarding APE1 (T>G), MLH1 (G>A) and CDH1-347 (G>GA) polymorphic alleles, were only linked to patients from Pará State. Protection was associated with CA of the CDH1-160 (C>A) in males from Ceará State. In summary, our data show that these SNPs are potentials markers of susceptibility to the different subtypes of GC, in which gender is also an important aspect.