Serum selenium and risk of prostate cancer-a nested case-control study

Abstract

Background: Selenium is a potential chemopreventive agent against prostate cancer, whose chemoprotective effects are possibly mediated through the antioxidative properties of selenoenzymes. Interrelations with other antioxidative agents and oxidative stressors, such as smoking, are poorly understood.

Objectives: The aims were to investigate the association between serum selenium and prostate cancer risk and to examine interactions with other antioxidants and tobacco use.

Design: A nested case-control study was performed within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Serum selenium in prospectively collected samples was compared between 724 incident prostate cancer case subjects and 879 control subjects, frequency-matched for age, time since initial screen, and year of blood draw. The men were followed for up to 8 y.

Results: Overall, serum selenium was not associated with prostate cancer risk (P for trend = 0.70); however, higher serum selenium was associated with lower risks in men reporting a high (more than the median: 28.0 IU/d) vitamin E intake [odds ratio (OR) for the highest compared with the lowest quartile of selenium: 0.58; 95% CI: 0.37, 0.91; P for trend = 0.05; P for interaction = 0.01] and in multivitamin users (OR for highest compared with the lowest quartile of selenium: 0.61; 95% CI: 0.36, 1.04; P for trend = 0.06; P for interaction = 0.05). Furthermore, among smokers, high serum selenium concentrations were related to reduced prostate cancer risk (OR for the highest compared with the lowest quartile of selenium: 0.65; 95% CI: 0.44, 0.97; P for trend = 0.09; P for interaction = 0.007).

Conclusion: Greater prediagnostic serum selenium concentrations were not associated with prostate cancer risk in this large cohort, although greater concentrations were associated with reduced prostate cancer risks in men who reported a high intake of vitamin E, in multivitamin users, and in smokers.

FIGURE 1

Clinical trial and observational studies on selenium and the risk of prostate cancer listed by mean or median selenium concentrations. ORs and 95% CIs were obtained in a comparison of the highest with the lowest quantile of selenium. ◆, randomized clinical trials with selenium concentrations obtained from serum or plasma; ▲, nested case-control study (CCS) and case cohort study with selenium concentrations obtained from serum or plasma; ●, population-based CCS with selenium concentrations obtained from serum or plasma; △, nested CCS and case cohort study with selenium obtained from toenails; ○, population-based CCS with selenium obtained from toenails. Observational studies were excluded if they used a questionnaire-based assessment of selenium intake, included patients with benign prostatic hyperplasia as controls, or included < 15 prostate cancer cases.

FIGURE 2

Observational studies on selenium and risk of advanced prostate cancer (1) listed by mean or median selenium concentrations. ORs and 95% CIs were obtained in a comparison of the highest with the lowest quantile of seleniuim. ▲, nested case-control study (CCS) and case cohort study with selenium concentrations obtained from serum or plasma; ●, population-based CCS with selenium concentrations obtained from serum or plasma; △, nested CCS and case cohort study with selenium concentrations obtained from toenails; ○, population-based CCS with selenium concentrations obtained from toenails. Observational studies were excluded if they used a questionnaire-based assessment of selenium intake, included patients with benign prostatic hyperplasia as controls, or included < 15 prostate cancer cases. Advanced cancer was defined as a tumor that extends through the prostatic capsule or as a metastatic disease (stage C or D, stage III or IV, or regional or distant stage); the exception was Vogt et al (55), who defined advanced cancer as regional or distant stage, Gleason Score ≥ 7, or both.