Vitamin A and Prostate CancerLaura Simonitchlsimonitch@kumc.eduB.S. University of Nebraska-LincolnDietetic Intern, MS StudentUniversity of Kansas Medical Center
Introduction Vitamin A is a fat-soluble vitamin1. Needed for vision, bone growth, reproduction, embryonicdevelopment, and for differentiation of epithelial tissues1. Retinoids2 Studies evaluated: serum retinol concentrations β-carotene + retinyl palmitate supplementation1. Trumbo P, et al. (2001)2. Mahan L, et al. (2012)RDA for males: 900 µg/dRDA for females: 700 µg/d
Purpose Belief that supplements will benefit healthand decrease risk for chronic diseases like3,4. Retinol’s role in growth, differentiation, andapoptosis53. White E, et al. (2004)4. Satia-Abouta J, et al. (2003)5. Peehl DM, et al. (2003)
Research Question What is the relationship between vitamin Aand risk for prostate cancer?
Review of the Literature6. Neuhouser M, et al. Dietary supplement use and prostate cancerrisk in the carotene and retinol efficacy trial. Cancer EpidemiolBiomarkers Prev. 20097. Mondul A, et al. Serum Retinol and Risk of Prostate Cancer. Am JEpidemiol. 20118. Schenk J, et al. Serum Retinol and Prostate Cancer Risk: a NestedCase-Control Study in the Prostate, Lung, Colorectal, and OvarianCancer Screening Trial. Cancer Epidemiol Biomarkers Prev. 2009PubMed search terms: “vitamin A AND prostate cancer”, randomizedcontrolled trials, published within the last 5 years, humanstudies, English language, Cancer subject, and adults 19years or older
ParticipantsStudy Type of Study Design Inclusion CriteriaNeuhouserM, et al.(2009)Randomized ControlledTrial, double-blindedplacebo-controlledAges 45-69, smokers, history of at least 20 pack-years of cigarette smoking who were current orformer smokers with exposure to asbestos withinlast 15 yearsMondul A,et al. (2011)Randomized, double-blind, placebo-controlled,primary prevention trialMales who smoke at least 5 cigarettes per day,between 50-69 years oldSchenk J,et al. (2009)Nested case-controlstudyCases (prostate cancer ): n = 692; Controls(matched controls): n = 844. Men randomized to thescreening arm of the PLCO trial who underwentprostate cancer screening by serum prostate-specific antigen (PSA) and digital rectal examination(DRE) at entry and annually
InterventionStudy Inclusion Criteria TreatmentGroup(s)/RegimenComparisonGroupNeuhouserM, et al.(2009)Ages 45-69, smokers, history of atleast 20 pack-years of cigarettesmoking who were current or formersmokers with exposure to asbestoswithin last 15 years30 mg β-carotene + 25,000 IUretinyl palmitate supplements(CARET vitamins) taken daily,n = 6,197Placebon = 5,803Mondul A,et al.(2011)Males who smoke at least 5cigarettes per day, between 50-69years oldα-tocopherol supplement (50mg/day), n = 480;β-carotene supplement (20mg/day), n = 531; α-tocopherol + β-carotenesupplements, n = 498Placebon = 532Schenk J,et al.(2009)Cases: n = 692; Controls: n = 844.Men who underwent prostate cancerscreening by PSA and DRE at entryand annuallyNone None
Results – Neuhouser M, et al. Men taking CARET vitamins + another dietarysupplement prostate cancer relative riskof 1.52 Declined to 0.75 post-intervention Findings were exclusively aggressive cancer Non-aggressive prostate cancer diagnosis,taking CARET vitamins with no othersupplements 35% reduced risk of cancer
Results Clinical significance High-dose of β-carotene + retinyl palmitate,with at least one other dietary supplement,may increase risk for aggressive prostatecancerNeuhouser M, et al. (2009).
Results – Mondul A, et al. Serum retinol concentration: more directmeasure of retinol status Quintile 5 significantly more prone to developprostate cancer during follow-up period thanQuintile 1Baseline Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5Serum retinol(µg/L)<483 483-546 547-606 607-684 ≥685BMI 25.6 26.1 26.3 26.5 26.8
Results Positive serum retinol-prostate cancer riskassociation greatest in: placebo group, α-tocopherol-only groups, highbaseline serum α-tocopherol, high baselineserum β-carotene, high total cholesterollevels, high dietary retinol intake 20% greater risk for men in highest retinolquintile for cancer overallMondul A, et al. (2011)
Results – Schenk J, et al.Serum retinol concentrations were not associatedwith overall prostate cancer riskSignificant 42% reduction in aggressivecancer risk for those with highest serum retinolconcentrationsBaseline Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5Serum retinol(µg/L)27.4-54.7 54.8-64.3 64.4-72.8 72.9-85.3 85.4-262.6BMI 27.8 27.9 27.3 26.9 26.9
ResultsShow protective association between serumretinol concentrations and risk of aggressiveprostate cancerOnly study to show inverse relationship inaggressive diseaseSchenk J, et al. (2009)
Limitations Participants in Neuhouser M, et al.’s studytook their own dietary supplements Smokers versus nonsmokers
Conclusions Mixed results… Retinol affected by CRBP9 Reason why circulating retinol may increaserisk is unknown9. Jerónimo C, et al. (2004)
Take Home Message Careful consideration if dietary supplement isneeded, especially if already at increased riskfor prostate cancer
References1. Trumbo, P. et al. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron,Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington D.C.: National Academy Press; 2001. AccessedMarch 10, 2013.2. Mahan L, Escott-Stump S, Raymond J. Krause’s Food and the Nutrition Care Process. Missouri: Elsevier Saunders; 2012.3. White E, Patterson RE, Kristal AR, et al. Vitamins And Lifestyle Cohort Study: study design and characteristics of supplementusers. Am J Epidemiol 2004;159:83–93. Available at:http://aje.oxfordjournals.org.proxy.kumc.edu:2048/content/159/1/83.full.pdf+html. Accessed on February 17, 2012.4. Satia-Abouta J, Kristal AR, Patterson RE, Littman AJ, Stratton KL, White E. Dietary supplement use and medical conditions -the VITAL study. Am J Prev Med 2003;24:43–51. Available at:http://www.sciencedirect.com.proxy.kumc.edu:2048/science/article/pii/ S0749379702005718. Accessed February 17, 2013.5. Peehl DM, Feldman D. The role of vitamin D and retinoids in controlling prostate cancer progression. Endocr Relat Cancer.2003;10(2):131–140. Available at: http://erc.endocrinology-journals.org.proxy.kumc.edu:2048/content/10/2/131.long. AccessedMarch 10, 2013.6. Neuhouser M, et al. Dietary supplement use and prostate cancer risk in the carotene and retinol efficacy trial. CancerEpidemiol Biomarkers Prev. 2009;18(8): 2202-2206.http://www.ncbi.nlm.nih.gov.proxy.kumc.edu:2048/pmc/articles/PMC2733330/pdf/nihms-137336.pdf. Accessed February 10,2013.7. Mondul A, et al. Serum Retinol and Risk of Prostate Cancer. Am J Epidemiol. 2011;173(7):813-821. Available at:http://www.ncbi.nlm.nih.gov.proxy.kumc.edu:2048/pmc/articles/PMC3105279/pdf/kwq429.pdf. Accessed February 9,2013.8. Schenk J, et al. Serum Retinol and Prostate Cancer Risk: a Nested Case-Control Study in the Prostate, Lung, Colorectal, andOvarian Cancer Screening Trial. Cancer Epidemiol Biomarkers Prev. 2009 April;18(4):1227-1231. Available at:http://www.ncbi.nlm.nih.gov.proxy.kumc.edu:2048/pmc/articles/PMC2717001/pdf/nihms109783.pdf. Accessed February 9, 2013.9. Jerónimo C, Henrique R, Oliveira J, et al. Aberrant cellular retinol binding protein 1 (CRBP1) geneexpression and promoter methylation in prostate cancer. J Clin Pathol 2004;57:872–6. Available at:http://jcp.bmj.com.proxy.kumc.edu:2048/content/57/8/872.long. Accessed March 10, 2013.
Thank you!Questions?Laura Simonitchlsimonitch@kumc.eduB.S. University of Nebraska-LincolnDietetic Intern, MS StudentUniversity of Kansas Medical Center
Strengths Neuhouser M, et al: excellent follow-upduring and after trial Mondul A, et al: large cohort and incidentcase sample size, measurement of serumretinol for entire cohort at 2 points in time(unlike most studies) Schenk J, et al: had standardized proceduresfor prostate cancer screening, a large samplesize, high compliance with protocol
Prostate Cancer Diagnosis Digital Rectal Examination Prostate-Specific Antigen Blood Test Prostate Ultrasound and Biopsy Cystoscopy or Bladder Scope Test:measures health of urethra and bladder CAT scan: x-rays to find swollen or enlargedlymph nodes MRIs: radio waves to examine prostate andnearby lymph nodes Prostate Cancer Health Center. WebMD website. Available at: http://www.webmd.com/prostate-cancer/guide/prostate-cancer-diagnosis-tests. Accessed April 15, 2013.
Prostate Cancer Treatment Surgery Radiation Hormone Therapy Chemotherapy (for those who don’t respondto hormone therapy) Cyrotherapy: freezing cancerous areas of theprostate Prostate Cancer Health Center. WebMD website. Available at: http://www.webmd.com/prostate-cancer/guide/prostate-cancer-treatment-care. Accessed April 15, 2013.
Statistics 2nd leading cause of cancer death inAmerican men, behind lung cancer ~238,590 new cases of prostate cancer willbe diagnosed in 2013 ~1 man in 6 will be diagnosed with prostatecancer during his lifetime, and ~1 man in 36will die from it Average age at the time of diagnosis is about67What are the key statistics about prostate cancer? American Cancer Society web site. Available at:http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-key-statistics.Accessed April 18, 2013.
Survival The relative 5-year survival rate is nearly100% The relative 10-year survival rate is 98% The 15-year relative survival rate is 93%American Cancer Society Web site. Survival rates for prostate cancer. Available at:http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-survival-rates. Accessed April 18,Stage 5-year relative survival rateLocal ~100%Regional ~100%Distant 28%