Association of the OGG1 ser326cys polymorphism with lung cancer risk and 8-OHdG levels as a biomarker of oxidative damage in Turkish population

Lung cancer is the most common cancer and has the highest mortality rate in the world. The dominant role of tobacco smoke as a causative factor in lung cancer has been well established. Environmental and genetic predisposition can also play an important role in development of lung cancer. The connection between smoking and these diseases is oxidative stress, a condition in which lipids, proteins and DNA are damaged by the reactive oxygen species. Reactive Oxygen Species (ROS) formed by exogeneously and endogeneously processes cause oxidative damage to DNA. 8-hydroxyguanine (8-OHG) is one of the major lesions and repaired by 8-oxoguanine DNA glycosylase (OGG1) which plays an important role in Base Excision Repair (BER) system. 8-OHG is highly mutagenic and, if not excised /repaired on DNA replication, can cause GC to TA transversion mutations. There are many conflicting studies which are showing the association between OGG1 activity and OGG1 Ser326Cys polymorphism. Thus, in this study, it was aimed to investigate the relation between OGG1 Ser326Cys polymorphism and the risk of lung cancer and to measure the levels of urinary 8-OHdG as a biomarker of oxidative DNA damage. One hundred sixty-five subjects with lung cancer and 250 healthy control subjects were genotyped by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR) for OGG1 Ser326Cys polymorphism. We could not find any association between OGG1 Ser326Cys polymorphism and the risk of lung cancer. It was also measured urinary 8- OHdG levels by ELISA immunoassay in patients (no received any chemotherapy and radiotherapy) and healthy control subjects. There was no significant difference between patients and control subjects. Surprisingly, our data demonstrated that subjects, with carrying variant genotype, who smoked more than 20 cigarettes /day were, decreased the risk of cancer. Investigating of the combined effects of polymorphisms within many DNA repair genes, measuring products of oxidative stress from smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.