Vitamin A and Prostate Cancer

Laura Simonitch

lsimonitch@kumc.edu

B.S. University of Nebraska-Lincoln

Dietetic Intern, MS Student

University of Kansas Medical Center

Introduction Vitamin A is a fat-soluble vitamin1. Needed for vision, bone growth, reproduction, embryonic

development, and for differentiation of epithelial tissues1. Retinoids2

Studies evaluated: serum retinol concentrations β-carotene + retinyl palmitate supplementation

1. 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 health and decrease risk for chronic diseases like3,4.

Retinol’s role in growth, differentiation, and apoptosis5

3. 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 A and risk for prostate cancer?

Review of the Literature6. Neuhouser M, et al. Dietary supplement use and prostate cancer risk in the carotene and retinol efficacy trial. Cancer Epidemiol Biomarkers Prev. 2009

7. Mondul A, et al. Serum Retinol and Risk of Prostate Cancer. Am J Epidemiol. 2011

8. Schenk J, et al. Serum Retinol and Prostate Cancer Risk: a Nested Case-Control Study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiol Biomarkers Prev. 2009

PubMed search terms: “vitamin A AND prostate cancer”, randomized controlled trials, published within the last 5 years, human studies, English language, Cancer subject, and adults 19 years or older

ParticipantsStudy Type of Study Design Inclusion Criteria

Neuhouser M, et al.  (2009)

Randomized Controlled Trial, double-blinded placebo-controlled 

Ages 45-69, smokers, history of at least 20 pack-years of cigarette smoking who were current or former smokers with exposure to asbestos within last 15 years 

Mondul A, et al.  (2011)

Randomized, double-blind, placebo-controlled, primary prevention trial 

Males who smoke at least 5 cigarettes per day, between 50-69 years old 

Schenk J, et al. (2009)

Nested case-control study

Cases (prostate cancer ): n = 692; Controls (matched controls): n = 844. Men randomized to the screening arm of the PLCO trial who underwent prostate cancer screening by serum prostate-specific antigen (PSA) and digital rectal examination (DRE) at entry and annually

InterventionStudy Inclusion Criteria Treatment

Group(s)/RegimenComparison

Group

Neuhouser M, et al. (2009) 

Ages 45-69, smokers, history of at least 20 pack-years of cigarette smoking who were current or former smokers with exposure to asbestos within last 15 years 

30 mg β-carotene + 25,000 IU retinyl palmitate supplements (CARET vitamins) taken daily, n = 6,197 

Placebon = 5,803 

Mondul A, et al. (2011)

Males who smoke at least 5 cigarettes per day, between 50-69 years old 

α-tocopherol supplement (50 mg/day), n = 480; β-carotene supplement (20 mg/day), n = 531; α-tocopherol + β-carotene supplements, n = 498 

Placebon = 532 

Schenk J, et al. (2009)

Cases: n = 692; Controls: n = 844. Men who underwent prostate cancer screening by PSA and DRE at entry and annually

None None

Results – Neuhouser M, et al.

Men taking CARET vitamins + another dietary supplement prostate cancer relative risk of 1.52 Declined to 0.75 post-intervention Findings were exclusively aggressive cancer

Non-aggressive prostate cancer diagnosis, taking CARET vitamins with no other supplements 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 prostate cancer

Neuhouser M, et al. (2009).

Results – Mondul A, et al.

Serum retinol concentration: more direct measure of retinol status

Quintile 5 significantly more prone to develop prostate cancer during follow-up period than Quintile 1

Baseline Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5

Serum retinol (µg/L)

<483 483-546 547-606 607-684 ≥685

BMI 25.6 26.1 26.3 26.5 26.8

Results

Positive serum retinol-prostate cancer risk association greatest in: placebo group, α-tocopherol-only groups, high

baseline serum α-tocopherol, high baseline serum β-carotene, high total cholesterol levels, high dietary retinol intake

20% greater risk for men in highest retinol quintile

for cancer overall

Mondul A, et al. (2011)

Results – Schenk J, et al.

Serum retinol concentrations were not associated with overall prostate cancer riskSignificant 42% reduction in aggressive cancer risk for those with highest serum retinol concentrations

Baseline Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5

Serum retinol (µg/L)

27.4-54.7 54.8-64.3 64.4-72.8 72.9-85.3 85.4-262.6

BMI 27.8 27.9 27.3 26.9 26.9

Results

Show protective association between serum retinol concentrations and risk of aggressive prostate cancer

Only study to show inverse relationship in aggressive disease

Schenk J, et al. (2009)

Limitations

Participants in Neuhouser M, et al.’s study took their own dietary supplements

Smokers versus nonsmokers

Conclusions Mixed results…

Retinol affected by CRBP9

Reason why circulating retinol may increase risk is unknown

9. Jerónimo C, et al. (2004)

Take Home Message

Careful consideration if dietary supplement is needed, especially if already at increased risk for 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. Accessed March 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 supplement users. 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. Accessed March 10, 2013.

6. Neuhouser M, et al. Dietary supplement use and prostate cancer risk in the carotene and retinol efficacy trial. Cancer Epidemiol 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, and Ovarian 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) gene

expression 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 Simonitch

lsimonitch@kumc.edu

B.S. University of Nebraska-Lincoln

Dietetic Intern, MS Student

University of Kansas Medical Center

Strengths

Neuhouser M, et al: excellent follow-up during and after trial

Mondul A, et al: large cohort and incident case sample size, measurement of serum retinol for entire cohort at 2 points in time (unlike most studies)

Schenk J, et al: had standardized procedures for prostate cancer screening, a large sample size, high compliance with protocol

Sources of Vitamin A

Sweet potatoes Carrots Dark, leafy greens Liver Beef

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 enlarged lymph nodes MRIs: radio waves to examine prostate and nearby 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 respond

to hormone therapy) Cyrotherapy: freezing cancerous areas of the

prostate 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 in American

men, behind lung cancer ~238,590 new cases of prostate cancer will be

diagnosed in 2013 ~1 man in 6 will be diagnosed with prostate cancer

during his lifetime, and ~1 man in 36 will die from it Average age at the time of diagnosis is about 67

What 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 nearly 100% 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, 2013.

Stage 5-year relative survival rate

Local ~100%

Regional ~100%

Distant 28%