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).


CONCLUSIONS
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.
Woodson
Karen
K
Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-7058, USA. kw114v@nih.gov
Tangrea
Joseph A
JA
Lehman
Teresa A
TA
Modali
Ramakrishna
R
Taylor
Kristin M
KM
Snyder
Kirk
K
Taylor
Philip R
PR
Virtamo
Jarmo
J
Albanes
Demetrius
D
D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D016022:Case-Control Studies; D005387:Finland; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics*; D024502:alpha-Tocopherol / Q000008:administration & dosage*; D019207:beta Carotene / Q000008:administration & dosage*
D000975:Antioxidants; D019207:beta Carotene; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol