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.

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)).