Selenium Supplements After Diagnosis of Nonmetastatic Prostate Cancer May Raise Prostate Cancer Mortality Risk

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“Selenium supplementation of 140 or more μg/d 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,” Stacey A. Kenfield, ScD, of the University of California, San Francisco, and coauthors 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 between the age of 40 and 75 at the time of enrollment in 1986. Participants completed a baseline questionnaire that included extensive data, such as a medical history and lifestyle factors (diet and supplement use), and 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. The categories of total selenium supplement dosage follow: nonuser, 1 to 24 μg/d, 25 to 139 μg/d, and 140 or more μg/d. “We also calculated total duration of use to assess whether the association between selenium supplement use and prostate cancer mortality differed by duration,” the authors noted.

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, the investigators obtained medical records “to confirm the diagnosis and record the clinical T stage, Gleason score, treatments, prostate-specific antigen (PSA) values at diagnosis, PSA levels after treatment (to identify events of biochemical tumor recurrence), and metastasis. Participants also completed biennial follow-up questionnaires to update data on treatments, PSA levels, and clinical progression,” the researchers explained.

“We documented 965 deaths, 226 (23.4%) from prostate cancer and 267 (27.7%) from cardiovascular disease, during a median follow-up of 8.9 years. In the biochemical recurrence analysis, we documented 762 tumor recurrences during a median follow-up of 7.8 years. Crude rates per 1,000 person-years for prostate cancer death were 5.6 among selenium nonusers and 10.5 among men who consumed 140 or more μg/d,” the researchers reported.

“In multivariable analyses, men who consumed 1 to 24 μg/d, 25 to 139 μg/d, and 140 or more 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. There were no statistically significant associations between the use of selenium supplements and biochemical recurrence, cardiovascular disease mortality, and overall mortality.

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 were taken prior to diagnosis.

“These data underscore the potentially complex and variable role that lifestyle factors may play in the long etiologic course of some cancers, in particular that risk factors for incidence may be very different from 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.” ■

Kenfield SA, et al: J Natl Cancer Inst 107:360, 2014 (print January 2015).