Selenium supplementation of 140 μg/d or more after diagnosis of nonmetastatic prostate cancer may increase risk of prostate cancer mortality, according to a prospective study following 4,459 men initially diagnosed with nonmetastatic prostate cancer in the Health Professionals Follow-up Study from 1988 through 2010. “Caution is warranted regarding usage of such supplements among men with prostate cancer,” Kenfield et al advised in the Journal of the National Cancer Institute.
The Health Professionals Follow-up Study is a prospective cohort study of 51,529 U.S. male health professionals who were between age 40 and 75 years at the time of enrollment in 1986. Participants completed a baseline questionnaire that included extensive data, including medical history and lifestyle factors such as diet and supplement use, and completed detailed information on the use and dose of supplements every 2 years.
“Total selenium supplement intake was calculated as the sum from multivitamins and selenium supplements,” the investigators explained. Total selenium supplement dosage was divided into four categories: nonuser, 1 to 24 μg/d, 25 to 139 μg/d, and ≥ 140 μg/d. “We also calculated total duration of use to assess whether the association between selenium supplement use and prostate cancer morality differed by duration,” the authors noted.
More Than Twofold Greater Risk
The primary outcome in the current study was prostate cancer mortality. Secondary outcomes were biochemical recurrence, overall mortality, and cardiovascular mortality. After study participants reported a prostate cancer diagnosis, investigators obtained medical records to confirm the diagnosis and record clinical T stage, Gleason score, treatments, prostate-specific antigen (PSA) values at diagnosis, PSA levels after treatment, and metastasis. Participants completed biennial follow-up questionnaires to update data on treatments, PSA levels, and clinical progression.
After a median follow-up of 8.9 years, 965 deaths, were reported; 226 (23.4%) of these were prostate cancer–related, and 267 (27.7%) were because of cardiovascular disease. The biochemical recurrence analysis revealed 762 recurrences after a median follow-up of 7.8 years.
Crude rates of prostate cancer–specific mortality were 5.6 per 1,000 person-years for among selenium nonusers and 10.5 per 1,000 person-years among those who consumed ≥ 140 mg/d. Multivariable analyses revealed that men who consumed 1 to 24 μg/d, 25 to 139 μg/d, and at least 140 μg/d of supplemental selenium had a 1.18 (95% confidence interval [CI] = 0.73–1.91), 1.33 (95% CI = 0.77–2.30), and 2.60-fold (95% CI = 1.44–4.70) greater risk of prostate cancer mortality compared with nonusers, respectively (Ptrend = .001), the authors reported.
There were no statistically significant associations between use of selenium supplements and biochemical recurrence, cardiovascular disease mortality, and overall mortality.
Complex Roles of Lifestyle Factors
The authors noted that their study “is the first study to examine the relation of selenium supplements taken after diagnosis with risk of prostate cancer mortality.” Findings from previous studies of selenium supplementation by healthy men have included an inverse relationship between selenium levels and incident-advanced prostate cancer, no association for incident prostate cancer, but an increased risk for high-grade prostate cancer, and an increased risk of prostate cancer mortality when selenium supplements are taken prior to diagnosis.
“These data underscore the potentially complex and variable role that lifestyle factors may play in the long etiologic time course of some cancers, in particular that risk factors for incidence may be very different than those for mortality,” the investigators observed. “Associations between a given exposure and incident prostate cancer presumably reflect biologic effects of the exposure in the prostate gland, whereas associations with metastatic/fatal disease may reflect effects of the exposure in the prostate (if the tumor is still present) and/or effects on other organs or systems that influence the likelihood of metastatic disease developing and spreading. Additional studies with long-term follow-up of lifestyle factors before and after cancer diagnosis are warranted.”
Stacey A. Kenfield, ScD, of the University of California, San Francisco, is the corresponding author for the Journal of the National Cancer Institute article.
The study was supported by grants from the National Cancer Institute, the Department of Defense, and the Prostate Cancer Foundation.
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