Investigating the role of oxidative DNA damage, DNA repair capacity and related genetic polymorphisms in individual susceptibility of Barrett?s esophagus

Determination of the genetic alterations, which play a role in the ethiology of the Barrett?s esophagus, will provide developing new biomarkers to protect the high risk population, against esophageal adenocarcinoma disease.The aim of our study was to investigate the role of oxidative DNA damage, GSH concentration as oxidative stress parameters and DNA repair capacity, GSTM1, MnSOD Ala16Val and hOGG1 Ser326Cys genetic polymorphisms as individual susceptibility parameters in the ethiology of Barrett?s esophagus. We have also investigated the relation of these two group of parameters. Our study was consisted of Barrett?s esophagus patients who are clinically diagnosed (n=40) and a healthy control group (n=40).Basal DNA damage, pyrimidine and purine base damage afer H2O2 induction, H2O2 sensitivity, DNA repair capacity%, oxidized pyrimidine and purine base damage repair%, were evaluated in peripheral blood lymphocytes with modified Comet assay by using spesific endonucleases (Endo III and Fpg). The patient group showed elevated levels of basal DNA damage and pyrimidine base damage as compared to control group (p<0,05). The H2O2 sensitivity was also elevated in patient group as compared to control group (p<0,05). DNA repair capacity%, oxidized pyrimidine and purine base damage repair capacity% were not statistically different between patient and control group (p>0,05). GSH concentration was found to be significantly lower in smoking patients than controls (p<0,05). None of the genetic variations either alone or in combination, changed the risk of having Barrett?s esophagus disease as determined with PCR-RFLP method. However, patients carrying the Cys mutant allele showed elevated levels of pyrimidine base damage, as compared to patients carrying Ser wild allele (p<0,05). In conclusion, the results of this study points out the role of oxidative DNA damage in Barrett?s esophagus however, DNA repair capacity, GSTM1, MnSOD Ala16Val and hOGG1 Ser326Cys genetic polymorphisms seem to have no effect on individual susceptibility in progressing the disease.