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

Cancer Causes Control. 2003 Aug;14(6):513-8. doi: 10.1023/a:1024840823328.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Antioxidants / administration & dosage*
  • Case-Control Studies
  • Finland
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic*
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / prevention & control
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Superoxide Dismutase / genetics*
  • alpha-Tocopherol / administration & dosage*
  • beta Carotene / administration & dosage*


  • Antioxidants
  • beta Carotene
  • Superoxide Dismutase
  • alpha-Tocopherol