Prostate cancer continues to be the most frequently diagnosed
neoplasm, and the second leading cause of
cancer-related mortality in men. Oxidative stress may enhance prostatic
carcinogenesis.
Manganese superoxide dismutase (MnSOD) is the only known
superoxide scavenger in mitochondria. It plays a key role in
antioxidant defense as mitochondria are important for oxidative metabolism coupled to the electron transport chain and oxidative phosphorylation and hence, ROS production. A T-->C single
nucleotide substitution, resulting in a Val-->Ala change at position 9 (Ala-9Val), which alters the secondary structure of the
protein, has been noted to affect transport of MnSOD into the mitochondria. We have determined the MnSOD genotype in 85
prostate cancer cases and 151 control subjects. Ala-9Val polymorphism was determined using real time polymerase chain reaction (PCR) amplification with fluorescently labeled primers. No significant difference was found in
prostate cancer susceptibility in the subjects with
Ala/Ala and Val/Ala genotype compared with
Val/Val genotype (Odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.69-2.42; p = 0.416). We did not observe an association of the MnSOD genotype or allele frequency between subgroups of cases divided by disease status (aggressive vs. non-aggressive
prostate cancer). However, in the analyses stratified by the age at diagnosis we have observed that men homozygous for Ala had a 5.2-fold increased risk of early-onset
prostate cancer (under age of 65) compared to men homozygous for Val allele (p = 0.05). These data suggest that
Ala/Ala MnSOD genotype in the Macedonian population could have an influence on early onset of
prostate cancer, but no impact on the subsequent development of the disease.