Vitamin E and the Vitamin E and the Risk of Prostate Risk of Prostate
CancerCancer
Vitamin E and the Vitamin E and the Risk of Prostate Risk of Prostate
CancerCancerThe Selenium and Vitamin E Cancer The Selenium and Vitamin E Cancer
Prevention Trial (SELECT)Prevention Trial (SELECT)The Selenium and Vitamin E Cancer The Selenium and Vitamin E Cancer
Prevention Trial (SELECT)Prevention Trial (SELECT)
Klein, Thompson, Tangen, et al. J Amer Med Assoc, Oct 12, 2011; Vol 306, Klein, Thompson, Tangen, et al. J Amer Med Assoc, Oct 12, 2011; Vol 306, No.14; 1549 - 1556No.14; 1549 - 1556
Zachary LapaquetteZachary LapaquettePharmD CandidatePharmD Candidate
University of GeorgiaUniversity of Georgia
Background
16% of men will be diagnosed with prostate cancer in their lifetime1
Most common type of cancer in U.S. men, other than non-melanoma skin cancer2
Second leading cause of cancer-related death in U.S. men
BackgroundBackground
Vitamin E is fat-soluble and has anti-oxidative properties
Recommended daily allowance for vitamin E is 22.4IU (15mg) daily3
Doses of 50IU/day were shown to decrease prostate cancer incidence in smokers4
SELECT TrialSELECT Trial
Randomized, placebo-controlled, multi-center trial
Compared selenium 200mcg/day, vitamin E 400IU/day, or both against placebo
Planned follow-up minimum of 7 years and maximum of 12 years
Inclusion CriteriaInclusion CriteriaHealthy
Age 50 or older for African Americans, or 55 for all other men
No h/o prostate cancer diagnosis
PSA < 4ng/mL
Normal DRE
No current use of anticoagulants
No h/o hemorrhagic stroke
Normal blood pressure
MethodsMethodsParticipants without prostate cancer had clinic visits every 6 months; with prostate cancer, annually
Annual PSA and DRE were not mandatory
Prostate cancer status was determined by self-report at each 6-month visit
Pathology report, tissue then sent to SELECT
MethodsMethods
Study was blinded until 10/23/2008, when participants discontinued use of study agents
Non-blinded follow-up occurred until 07/2011
Statistical AnalysisStatistical Analysis
Primary end point: Prostate cancer incidence as determined by routine clinical management
Other areas of study: colorectal cancer, lung cancer, all other primary cancers, deaths (all cause), development of diabetes, CVE
1- and 2-sided P values given
Statistical AnalysisStatistical Analysis
Proportional hazards model used
Unlike linear regression, proportional hazards models do not assume normal distribution and allow for censored data
Men without end-point of interest were censored at last contact date
Chi-squared test used to test the difference in the relative risk of diabetes
ResultsResults
Total of 35,533 men randomized at 427 centers into placebo (n=7594 had final follow-up data), vitamin E (n=7650), selenium (n=7626), selenium +vitamin E (n=7620)
No significant differences in age, race, baseline PSA, or diagnostic testing
ResultsResultsPlacebo
(n=8696)Vitamin E (n=8737)
Selenium (n=8752)
Vitamin E + Selenium (n=8702)
No. of prostate cancers
529 620 575 555
Hazard ratio (99% CI)
1.17 (1.004-1.36)
1.09 (0.93-1.27) 1.05 (0.89-1.22)
P value 0.008 0.18 0.46
Absolute Risk
9.3 10.9 10.1 9.7
Gleason >7, No. 133 155 161 164
Hazard Ratio (99% CI)
1.16 (0.86-1.58) 1.21 (0.9-1.63) 1.23 (0.91-1.66)
P value 0.20 0.11 0.08
ResultsResultsPlacebo
(n=8696)Vitamin E (n=8737)
Selenium (n=8752)
Vitamin E + Selenium (n=8702)
All cancers 1108 1190 1132 1149
Hazard ratio (99% CI)
1.07 (0.96-1.19) 1.02 (0.92-1.14 1.02 (0.92-1.14
P value 0.13 0.59 0.60
Diabetes 869 918 913 875
Relative risk (99% CI)
1.05 (0.93-1.17) 1.04 (0.93-1.17) 0.99 (0.89-1.12)
P value 0.29 0.34 0.91
Authors’ CommentAuthors’ Comment
An explanation for the increased risk of prostate cancer in the vitamin E arm is not apparent
The insignificant increased risk in the vitamin E + selenium arm implies that selenium may have a protective effect
This study is seems to contradict ATBC and PHS II studies
Caution should be used when recommending or studying high doses of micronutrients
Health effects from these agents may continue even after the intervention is stopped
ConclusionConclusion
Healthy men with average risk of prostate cancer subjected to contemporary community standards of screening and biopsy who took a common dose of vitamin E have a significantly increased risk of prostate cancer.
The increased risk implies that seemingly innocuous yet biologically active substances such as vitamins can cause harm
Consumers need be skeptical of health claims for unregulated over-the-counter products in the absence of strong evidence of benefit
Presenter’s Comment
Presenter’s Comment
Study has good reach, but is limited to healthy men 50+ years old
Criticism of study:
Did not have best- and worst-case censure analysis
Data collection dependent on self-report
427 research sites
Overall strong study
Placebo event rate: 529/8696 = 0.0608
Presenter’s Comment
Presenter’s Comment
NNH = 98
Vit E prostate cancer rate: 620/8737 = 0.0710
Placebo prostate cancer rate: 529/8696 = 0.0608
Works CitedWorks Cited
1.Klein, Thompson, Tangen, et al. Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial. J Amer Med Assoc, Oct 12, 2011; Vol 306, No.14; 1549 - 1556
2.National Cancer Institute. “A Snapshot of Prostate Cancer.” Sep 2010 <http://www.cancer.gov/aboutnci/servingpeople/snapshots/prostate.pdf>
3.National Institutes of Health. “Dietary Supplement Fact Sheet: Vitamin E.” Oct 2011 <http://ods.od.nih.gov/factsheets/VITAMINE>
4.Heinonen et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 1998 Mar 18;90(6):440-6.