Originally published as JCO Early Release 10.1200/JCO.2008.18.8938 on June 15 2009

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Plasma Selenium, Manganese Superoxide Dismutase, and Intermediate- or High-Risk Prostate Cancer

June M. Chan, William K. Oh, Wanling Xie, Meredith M. Regan, Meir J. Stampfer, Irena B. King, Miyako Abe, Philip W. Kantoff

From the Departments of Epidemiology and Biostatistics and Urology, University of California, San Francisco, San Francisco, CA; Lank Center for Genitourinary Oncology, and Departments of Biostatistics and Computational Biology and Medical Oncology, Dana-Farber Cancer Institute; Harvard Medical School; Channing Laboratory, Brigham and Women's Hospital and Harvard School of Public Health, Boston, MA; and Fred Hutchinson Cancer Research Center, Seattle, WA.

Corresponding author: June M. Chan, ScD, Helen Diller Family Cancer Research Building, 1450 3rd St, MC 3110, PO Box 589001, San Francisco, CA 94158-9001; e-mail: june.chan{at}ucsf.edu.

Purpose In vitro, in vivo, and epidemiologic studies support a role for selenium in reducing the risk of prostate cancer. Our group previously demonstrated a strong interaction between plasma selenium and the manganese superoxide dismutase (SOD2) gene and incident prostate cancer risk. We now hypothesized that SOD2 modifies the association between selenium level and risk of aggressive prostate cancer at diagnosis.

Patients and Methods We assessed SOD2 variants and plasma selenium in 489 patients with localized/locally advanced prostate cancer from an ongoing retrospective cohort. Cross-sectional associations with aggressive prostate cancer (ie, stage T2b-3, prostate-specific antigen > 10 ng/mL, or biopsy Gleason score 7) were evaluated using the ² test, Cochran-Armitage test for trend, and estimations of relative risk (RR) and 95% CIs.

Results SOD2 genotype alone was not associated with disease aggressiveness, whereas higher versus lower selenium levels were associated with a slightly increased likelihood of presenting with aggressive disease (RR = 1.35; 95% CI, 0.99 to 1.84). There was evidence of an interaction between SOD2 and selenium levels such that among men with the AA genotype, higher selenium levels were associated with a reduced risk of presenting with aggressive disease (RR = 0.60; 95% CI, 0.32 to 1.12), whereas among men with a V allele, higher selenium levels were associated with an increased risk of aggressive disease (for VV or VA men, RR = 1.82; 95% CI, 1.27 to 2.61; P for interaction = .007).

Conclusion These data suggest that the relationship between circulating selenium levels at diagnosis and prognostic risk of prostate cancer is modified by SOD2 genotype and indicate caution against broad use of selenium supplementation for men with prostate cancer.

J.M.C. and W.K.O. contributed equally to this work.

Supported by National Cancer Institute/National Institutes of Health Grant No. R01 CA106947; Prostate Cancer Specialized Programs of Research Excellence (SPORE) Grants No. P50CA90381 to Dana-Farber Harvard Cancer Center and P50CA89520 to University of California, San Francisco from the National Institutes of Health/National Cancer Institute; American Association for Cancer Research and the California Department of Public Health Early Career Development Award; Prostate Cancer Foundation; and The Arthur and Linda Gelb Center.

Presented in part at the American Society of Clinical Oncology Genitourinary Cancer Symposium, February 14-16, 2008, San Francisco, CA; and at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL.

The funding agencies provided financial support for this work but were not directly involved in the design of the study, collection of data, analysis, interpretation, decisions regarding publication, or writing of the article.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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