Cancer Causes & Control

, Volume 14, Issue 6, pp 513–518

Manganese superoxide dismutase (MnSOD) polymorphism, α-tocopherol supplementation and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (Finland)

Authors

    • Cancer Prevention Studies Branch, Center for Cancer ResearchNational Cancer Institute
  • Joseph A. Tangrea
    • Cancer Prevention Studies Branch, Center for Cancer ResearchNational Cancer Institute
  • Teresa A. Lehman
    • BioServe Biotechnologies
  • Ramakrishna Modali
    • BioServe Biotechnologies
  • Kristin M. Taylor
    • BioServe Biotechnologies
  • Kirk Snyder
    • Information Management Services, Inc.
  • Philip R. Taylor
    • Cancer Prevention Studies Branch, Center for Cancer ResearchNational Cancer Institute
  • Jarmo Virtamo
    • Department of Epidemiology and Health PromotionNational Public Health Institute
  • Demetrius Albanes
    • Nutritional Epidemiology Branch, Division of Cancer Epidemiology and GeneticsNational Cancer Institute
Article

DOI: 10.1023/A:1024840823328

Cite this article as:
Woodson, K., Tangrea, J.A., Lehman, T.A. et al. Cancer Causes Control (2003) 14: 513. doi:10.1023/A:1024840823328

Abstract

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 (α-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 α-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.

antioxidantsATBC Studymanganese superoxide dismutaseprostate cancerα-tocopherol
Download to read the full article text

Copyright information

© Kluwer Academic Publishers 2003