Polymorphisms in Turkish population

Association between manganese superoxide dismutase polymorphism and risk of lung cancer.

Department of Biochemistry, Faculty of Pharmacy, Istanbul University, 34116, Beyazit Istanbul, Turkey.

Manganese superoxide dismutase (MnSOD) is one of the major enzymes responsible for the defense against oxidative damage due to reactive oxygen species (ROS) in the mitochondria. C–>T substitution in the MnSOD gene (SOD2) produces an Ala–>Val change at amino acid 16, in the mitochondrial targeting sequence of the MnSOD precursor. This seems to reduce transport of the enzyme into mitochondria, decreasing its defense capacity against oxidative stress. The present case-control study was conducted to investigate the association of SOD2 genetic polymorphism with individual susceptibility to lung cancer. Ala16Val polymorphisms were determined using polymerase chain reaction, restriction fragment length polymorphism mapping, and agarose gel electrophoresis techniques in 100 lung cancer patients and 50 healthy control subjects. The frequency of the Val allele (OR=1.297, 95% CI=1.095-1.536) and the Val/Val genotype (OR=7.00, 95% CI=2.282-21.476) was significantly higher in lung cancer patients than in control subjects. There was a combined effect of Val/Val genotype as a genetic factor with smoking as an environment factor (OR=2.24). The increase in risk of lung cancer was lesser with this combined effect than with the Val/Val genotype alone. Thus, the Val/Val genotype of SOD2 may be associated with lung cancer in a Turkish population.

The association of OGG1 Ser326Cys polymorphism and urinary 8-OHdG levels with lung cancer susceptibility: a hospital-based case-control study in Turkey.

Faculty of Pharmacy, Department of Toxicology, Gazi University, Ankara, Turkey. bensuka@gmail.com

High incidence and poor prognosis of lung cancer make it a major health problem worldwide. Although smoking is a major cause of lung cancer, only some smokers develop lung cancer, which suggests that there is a genetic predisposition in some individuals. 8-OHG is an important oxidative base lesion and may elevate due to cancer and smoking. It is repaired by 8-hydroxyguanine DNA glycosylase 1 (OGG1), which has several polymorphisms. Although the Ser326Cys polymorphism is consistently associated with a range of cancers, findings about this polymorphism and lung cancer risk are contradictory. To date, no study has examined this association in the Turkish population. We conducted a case-control study to investigate the association between OGG1 Ser326Cys polymorphism and the risk of lung cancer using PCR-RFLP. We also evaluated gene-smoking interaction and excretion of urinary 8-OHdG. Our results suggest that the OGG1 Ser326Cys polymorphism is not a genetic risk factor for lung cancer, and that the heterozygous genotype is associated with a significantly reduced risk for lung cancer. The levels of 8-OHdG did not correlate with the polymorphism and smoking. Larger association studies are needed to validate our findings, and mechanistic studies are needed to elucidate the underlying molecular mechanisms of this association.

Yedikule Teaching Hospital for Chest Diseases and Thoracic Surgery, Istanbul, Turkey. dradalet@hotmail.com

Polymorphisms for genes encoding the metabolic enzymes cytochrome P450 1A1 (CYP1A1) might contribute to the variability in individual susceptibility to lung cancer. The role of CYP1A1 in lung carcinogenesis might be more important at low levels of exposure to carcinogens. In our study, CYP1A1 gene polymorphisms were investigated in healthy subjects and lung cancer patients in Turkish population. This case-control study encompassed 31 lung cancer patients and randomly selected 37 healthy individuals in control group. DNA samples, extracted from the whole blood were amplified using polymerase chain reaction (PCR) method. The prevalence of CYP1A1 Msp1 (-/+ or +/+) polymorphism in the lung cancer patients was 19.4%, compared to 16.2% in control group but the result was not statistically significant (OR= 1.24, 95% CI= 0.36-4.32, p= 0.74). Another important result obtained in this study is that 16.2% of Turkish population carries a CYP1A1 Msp1 polymorphism. The analysis of patients by histological type of lung cancer showed no association between histopathologic type of lung cancer and CYP1A1 Msp1 polymorphism (p= 0.6). Genetic researches using specific biomarkers are expected to be helpful in monitorizing the risk of lung cancer. Multicenter cohort studies are necessary to be able to obtain reliable and correct statistical information.