Article

Cancer Causes & Control

, Volume 14, Issue 6, pp 513-518

First online:

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

  • Karen WoodsonAffiliated withCancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute Email author 
  • , Joseph A. TangreaAffiliated withCancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute
  • , Teresa A. LehmanAffiliated withBioServe Biotechnologies
  • , Ramakrishna ModaliAffiliated withBioServe Biotechnologies
  • , Kristin M. TaylorAffiliated withBioServe Biotechnologies
  • , Kirk SnyderAffiliated withInformation Management Services, Inc.
  • , Philip R. TaylorAffiliated withCancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute
  • , Jarmo VirtamoAffiliated withDepartment of Epidemiology and Health Promotion, National Public Health Institute
  • , Demetrius AlbanesAffiliated withNutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute

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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.

antioxidants ATBC Study manganese superoxide dismutase prostate cancer α-tocopherol