Polymorphisms in Turkish population

Department of Toxicology, University of Gazi, Pharmacy Faculty, Ankara, Turkey. neslihan@gazi.edu.tr

Within mitochondria, manganese superoxide dismutase (MnSOD) provides a major defence against oxidative damage by reactive oxygen species (ROS). An alanine-9valine (Ala-9Val) polymorphism in the mitochondrial targeting sequence of MnSOD has been described and has recently been associated with risk of human breast cancer. Our present case-control study was performed to explore the association between MnSOD genetic polymorphism and individual susceptibility to breast cancer. Ala-9Val polymorphism in the signal sequence of the protein for MnSOD was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a study population. There was no significant difference in risk for breast cancer development between patients positive and negative for the MnSOD Ala allele with adjusted odds ratio (OR): 0.86 (95% confidence interval (CI(0.43 to 1.72). When MnSOD Ala was combined with either cytochrome P450 1B1 CYP1B1*1 and catechol O-methyltransferase COMT-L (V158M) genotypes, the risk for developing breast cancer was significantly increased in patients with a body mass index (BMI) greater than 24 kg m(-2) (OR: 1.42 (95%CI=1.04-1.93)).

Department of Toxicology, Faculty of Pharmacy (Eczacilik), Gazi University, 06330, Hipodrum Ankara, Turkey. bensu@gazi.edu.tr

Oxidative DNA damage, caused by either endogenous or exogenous sources of reactive oxygen species (ROS), has been linked to aging, chronic degenerative diseases, inflammatory diseases and cancers. 8-Hydroxydeoxyguanine (8-OHdG) is a major lesion produced by ROS. Among various types of DNA base modifications, 8-OHdG has been the most widely studied and is considered a key biomarker of oxidative DNA damage. Human 8-oxoguanine DNA glycosylase 1 (hOGG1) is a key component of the base excision repair (BER) pathway and catalyzes the removal of 8-OHdG. Ethnic and inter-individual differences in hOGG1 activity and several kinds of polymorphisms at the hOOG1 gene locus have been observed in the different populations studied so far. Since no information is available on the inter-individual variability of the hOGG1 genotype in the Turkish population, we genotyped 206 healthy, unrelated Turkish individuals. The allelic frequencies of the hOGG1 gene in the Turkish population were found to be 0.50, 0.41 and 0.09 (Ser/Ser, Ser/Cys and Cys/Cys, respectively). Our results are similar to those for Caucasians studied previously but are different from Asian populations. It seems that there is a growing need for extensive genotype studies with respect to the hOGG1 gene due to its importance to various types of cancer and to smoking habits.