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Woodson, K. et al.

Woodson, Tangrea, Lehman, Modali, Taylor, Snyder, Taylor, Virtamo, Albanes,

Manganese superoxide dismutase (MnSOD) polymorphism, alpha-tocopherol supplementation and prostate cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study (Finland).

OBJECTIVE: Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that plays a key role in protecting the cell from oxidative damage. A polymorphism in the mitochondrial targeting sequence (a valine to alanine substitution), thought to alter transport of the enzyme into mitochondria, has been associated with increased risk for breast cancer with a more pronounced association among women with low intake of dietary antioxidants. We examined the role of MnSOD in the development of prostate cancer in a large, randomized cancer prevention trial of male smokers, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We hypothesized that MnSOD may be associated with prostate cancer and that long-term antioxidant supplementation (alpha-tocopherol 50 mg/day for five to eight years) could modify the effect on risk. METHODS: Logistic regression was used to estimate these associations among 197 cases and 190 controls genotyped and matched for age, intervention group, and clinic. RESULTS: Men homozygous for the MnSOD ala allele had a 70% increase in risk over men homozygous for the val allele (odds ratio, OR = 1.72, 95% confidence interval, CI = 0.96-3.08, p = 0.07). Supplementation with alpha-tocopherol had no impact on the MnSOD-prostate cancer association. Although there was no difference in the association with disease stage, men homozygous for MnSOD ala (compared to MnSOD val/val or val/ala) showed a three-fold risk increase for high-grade tumors (OR = 2.72, 95% CI: 1.15-6.40, p = 0.02). CONCLUSION: These data suggest an effect of the MnSOD ala/ala genotype on the development of prostate cancer. Our observation of a stronger association with high-grade tumors may have prognostic implications that should also be pursued.[1]

References

Manganese superoxide dismutase (MnSOD) polymorphism, alpha-tocopherol supplementation and prostate cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study (Finland). Woodson, K., Tangrea, J.A., Lehman, T.A., Modali, R., Taylor, K.M., Snyder, K., Taylor, P.R., Virtamo, J., Albanes, D. Cancer Causes Control (2003) [Pubmed]

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