Plasma selenium, manganese superoxide dismutase, and intermediate- or high-risk prostate cancer.
OBJECTIVE
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.


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 > or = 7) were evaluated using the chi(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).


CONCLUSIONS
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.
Chan
June M
JM
Department of Epidemiology, University of California, San Francisco, San Francisco, CA, USA. june.chan@ucsf.edu
Oh
William K
WK
Xie
Wanling
W
Regan
Meredith M
MM
Stampfer
Meir J
MJ
King
Irena B
IB
Abe
Miyako
M
Kantoff
Philip W
PW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001707:Biopsy, Needle; D015331:Cohort Studies; D016001:Confidence Intervals; D003430:Cross-Sectional Studies; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D018570:Risk Assessment; D012643:Selenium / Q000097:blood*; D013482:Superoxide Dismutase / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D000099156:Superoxide Dismutase 2
D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen; D012643:Selenium; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2