Carcinogenesis Advance Access published online on September 10, 2008
Carcinogenesis, doi:10.1093/carcin/bgn212
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Manganese Superoxide Dismutase (MnSOD) Gene Polymorphism, Interactions with Carotenoid Levels, and Prostate Cancer Risk
1 Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115
2 Department of Nutrition, Harvard School of Public Health, Boston, MA 02115
3 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115
4 Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115
5 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205
6 Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801
Correspondence to: Edward Giovannucci, Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115; Tel: 617-432-4648, Fax: 617-432-2435, Email: egiovann{at}hsph.harvard.edu.
Background: The manganese superoxide dismutase (MnSOD) gene encodes an antioxidant enzyme (SOD2) that may protect cells from oxidative damage. The MnSOD allele with Val as amino acid 16 encodes a protein that has 30–40% lower activity compared to the MnSOD variant, hence possibly increasing susceptibility to oxidative stress. On the other hand, some epidemiologic studies suggest that the Ala allele is associated with a higher risk of cancer, including prostate cancer.
Methods: We conducted a nested case-control study in the Health Professionals Follow-up Study with 612 incident prostate cancer cases and 612 matched controls to investigate the role of the MnSOD gene Ala16Val polymorphism and its joint association with plasma carotenoid concentrations in relation to risk of total prostate cancer and aggressive prostate cancer (advanced stage or Gleason sum 
7).
Results: The allele frequencies in the controls were 49.8% for Ala and 50.2% for Val. No association was found between the MnSOD genotype and risk of total and aggressive prostate cancer. Furthermore, no statistically significant interaction was observed between the MnSOD genotype and any of the plasma carotenoids in relation to risk of total and aggressive prostate cancer. In analyses in which we combined data from plasma and dietary carotenoids and created a quintile score to reflect long-term carotenoid status, a 3-fold (95% CI: 1.37-7.02) increased risk of aggressive prostate cancer was observed among men with the Ala/Ala genotype in the presence of low long-term lycopene status (p-value, test for interaction = 0.02) as compared with men with the Ala/Val + Val/Val genotypes with low long-term lycopene status.
Conclusion: In this cohort of mainly white men, the MnSOD gene Ala16Val polymorphism was not associated with total or aggressive prostate cancer risk. However, men with the MnSOD Ala/Ala genotype who had low long-term lycopene status had a higher risk of aggressive prostate cancer compared to individuals with the other genotypes. These results are consistent with findings from earlier studies that reported when antioxidant status is low, the MnSOD Ala/Ala genotype may be associated with an increased risk of aggressive prostate cancer.
Key Words: prostate cancer • MnSOD gene polymorphism • plasma carotenoid levels
Support: This work is supported by Public Health Service Grants: CA 55075 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official view of NCI or the National Institutes of Health.
Received July 14, 2008; revised August 29, 2008; accepted September 3, 2008.
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