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

Abstract

A B S T R A C T PurposeIn 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 MethodsWe 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 Ͼ 10 ng/mL, or biopsy Gleason score Ն 7) were evaluated using the 2 test, Cochran-Armitage test for trend, and estimations of relative risk (RR) and 95% CIs. Results SOD2genotype 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 ϭ 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 ϭ 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 ϭ 1.82; 95% CI, 1.27 to 2.61; P for interaction ϭ .007). ConclusionThese 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.

Altered Trace Elements Levels in Hair of Prostate Cancer Patients

“…Additionally, several studies showed that Zn supplement may protect against free radical damage [16] or that Zn levels are decreased in patients with certain malignancies [17]. Se and Zn levels have been correlated to prostate cancer risk [18,19]; higher Se levels are related to a lower risk of many types of neoplasms, including lung, colorectal, prostate and possibly bladder [20,21]. Selenium is thought to inhibit carcinogenesis through many mechanisms including reduction of oxidative stress and inflammation, enhancement of the immune response, induction of apoptosis and cell cycle arrest as well as transactivation of DNA repairing genes [22,23].…”

Chemoprevention of prostate cancer: breakthroughs and controversies

“…At the median overall follow-up of 5.46 years, hazard ratios (HRs) were higher, but not significantly so, for vitamin E (HR: 1.13; 99% CI: 0.95-1.35), selenium (HR: 1.04; 99% CI: 0.87-1.24) and vitamin E and selenium (HR: 1.05; 99% CI: 0.88-1.25) compared with placebo. Emerging data suggest that the chemopreventive effects of selenium may be dependent on the genetic variants of selenoproteins [18,19]. Archived tissue and blood from the SELECT trial are expected to help unravel these questions.…”

Chemoprevention of prostate cancer with nutrients and supplements

“…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: 0.32-1.12), 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: 1.27-2.61; P for interaction , 0.007). 12 Finally, it may be hypothesized that the positive effects of selenium in the NPC study and the positive effects of vitamin E on PCa incidence in the ATBC trial could have been due to chance in secondary analyses. In addition, recently published results from the Prostate Cancer Prevention Trial found no significant association between vitamin E and selenium and the incidence of PCa.…”