Vitamin E and Selenium and Prostate Cancer Risk Michelle Gelfand Department of Nutrition Sciences Drexel University

Outline Background Information: -Vitamin E -Prostate Cancer Purpose Methods Results Conclusions Limitations Related studies Future Research Summary

Vitamin E Alpha tocopherol Good Sources: Plant oils, margarine, peanut butter, salad dressing Mainly absorbed in jejunum: Bile salts->forms micelles->passive diffusion into enterocyte->chylomicrons->lymph-> circulation->tissues->cells Found in adipose tissue, liver, lungs, heart Gropper, S. S., Smith, J. L., Groff, J. L., (2009). The Fat-Soluble Vitamins. In P. Adams & A. Lustig (Eds.), Advanced nutrition and human metabolism (pp ). Belmont, CA: Wadsworth.

Vitamin E Function Antioxidant Protects the membranes of cells Prevents oxidation of unsaturated fatty acids Hydroxyl group on phenol ring allows a proton to be donated to free radicals Can inactivate a single molecule of oxygen in a process called quenching Gropper, S. S., Smith, J. L., Groff, J. L., (2009). The Fat-Soluble Vitamins. In P. Adams & A. Lustig (Eds.), Advanced nutrition and human metabolism (pp ). Belmont, CA: Wadsworth.

Prostate Cancer 2nd leading cause of cancer death for men after lung cancer Most common cancer found in men besides skin cancer The cancer mainly occurs in the prostate’s gland cells Gland cells make fluid that is added to semen which nourishes and protects sperm cells American Cancer Society. (2011). What are the key statistics about prostate cancer? Retrieved from /DetailedGuide/ prostate-cancer-key-statistics

Gonzalgo, M. L., & Isaacs, W. B. (2003). Molecular pathways to prostate cancer. Journal of Urology, 170, 2444–52.

Diagnosing Prostate Cancer PSA (prostate-specific antigen) blood test -less than 4 ng/mL is considered normal DRE (digital rectal exam) -prostate is located in front the rectum -looking for bumps or hard areas Prostate biopsy -one or both of the above is abnormal -determines if sample cells are cancerous American Cancer Society. (2011). How is prostate cancer found? Retrieved from overview-diagnosed

Research Study Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trail (SELECT) Klein, E.A., Thompson Jr., I.M., Tangen, C.M. & et al. Journal of the American Medical Association 2011, Volume 306, Issue 14,

Purpose Determine long-term effects of vitamin E and selenium supplementation on prostate cancer risk in relatively healthy men. Klein, E. A., Thompson Jr., I. M., Tangen, C.M., Crowley, J. J., Lucia, M. S., Goodman, P.J.,... Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association, 306(14),

Background This study is a follow-up from the original contribution that was published in 2009 Original study’s objective was to determine if supplementing with vitamin E or selenium or both could prevent prostate cancer Supplementation was discontinued in 2008 due to results indicating no positive effect on decreasing cancer risk Lippman, S. M., Klein, E. A., Goodman, P. J., Lucia, M. S., Thompson, I. M., Ford, L. G.,... Coltman Jr., C. A. (2009). Effect of selenium and vitamin E on risk of prostate cancer and other cancers: The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association, 301(1),

Participant Selection Healthy men: Normal BP Restricted use of anticoagulants No history of stroke and cancer Age: 50 years and older if black 55 years and older if white PSA (prostate-specific antigen) of 4.0 ng/mL or less Normal DRE (digital rectal exam) Klein, E. A., Thompson Jr., I. M., Tangen, C.M., Crowley, J. J., Lucia, M. S., Goodman, P.J.,... Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association, 306(14),

Methods 427 sites in US, Canada, and Puerto Rico Randomized between Aug June 2004 Final data is from July 2011 Subjects were to follow up from a minimum of 7 and maximum of 12 years Monitored health history every 6 months Prostate cancer cases were confirmed by obtaining medical records Klein, E. A., Thompson Jr., I. M., Tangen, C.M., Crowley, J. J., Lucia, M. S., Goodman, P.J.,... Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association, 306(14),

Study Design Total: 35, 533 Men Vitamin E & Selenium 8,863 Vitamin E 8,904 Selenium 8,910 Placebo 8,856 Klein, E. A., Thompson Jr., I. M., Tangen, C.M., Crowley, J. J., Lucia, M. S., Goodman, P.J.,... Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association, 306(14),

Supplement Information Selenium: -200 mcg from L-selenomethionine -RDA: 55mcg UL: 200mcg Vitamin E: -400 IU (180mg) of all rac-alpha- tocopheryl acetate -RDA: 15 mg & UL: 1000 mg Klein, E. A., Thompson Jr., I. M., Tangen, C.M., Crowley, J. J., Lucia, M. S., Goodman, P.J.,... Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association, 306(14),

Results Supplementation with Vitamin E alone increased risk of prostate cancer significantly. P=.008 No increased risk of cancer when selenium alone or vitamin E and selenium are taken together Did not find increased risk of other cancers No benefit to supplementation Klein, E. A., Thompson Jr., I. M., Tangen, C.M., Crowley, J. J., Lucia, M. S., Goodman, P.J.,... Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association, 306(14),

Incidence of Prostate Cancer

GroupVitamin ESeleniumBothPlaceboTotal Cases P value Hazard ratio Klein, E. A., Thompson Jr., I. M., Tangen, C.M., Crowley, J. J., Lucia, M. S., Goodman, P.J.,... Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association, 306(14),

Conclusions Supplementing with vitamin E alone significantly increased prostate cancer risk No benefit to supplementing with vitamin E and/or selenium Even after a supplement is discontinued negative health outcomes may occur Klein, E. A., Thompson Jr., I. M., Tangen, C.M., Crowley, J. J., Lucia, M. S., Goodman, P.J.,... Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association, 306(14),

Limitations Did not explain WHY vitamin E increases prostate cancer risk “A biological explanation for the observed increased risk of prostate cancer in the vitamin E arm is not apparent from these data” Self report reliability Diet and lifestyle factors not included Klein, E. A., Thompson Jr., I. M., Tangen, C.M., Crowley, J. J., Lucia, M. S., Goodman, P.J.,... Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association, 306(14),

Findings From Other Studies 1.Alpha-Tocoperol, Beta Carotene Cancer Prevention (ATBC) Trial Findings: Decreased risk of prostate cancer w/ vitamin E supplementation in smokers 2.Physicians’ Health Study II Findings: Vitamin E supplementation did not decrease risk of prostate cancer Massachusetts Medical Society (1994). The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers: The alpha-tocopherol, beta carotene cancer prevention study group. New England Journal of Medicine, 330(15), Gaziano, J. M., Glynn, R. J., Christen, W. G., Kurth, T., Belanger, C., MacFadyen, J.,... Buring, J. E. (2009). Vitamin E and C in the prevention of prostate and total cancer in men: The physicians’ health study II randomized controlled trial. Journal of the American Medical Association, 301(1),

Future Research Recommendations If obtaining adequate vitamin E from foods alone can decrease prostate cancer risk Exploring the biochemical mechanism of WHY vitamin E increases risk of prostate cancer Studying vitamin E and cancer risk on other populations

Summary Supplementation with vitamin E or selenium does not decrease the risk of prostate cancer Vitamin E increased the risk of prostate cancer Best to obtain nutrients from foods because supplements have the potential to be harmful

Thank You Questions?

References American Cancer Society. (2011). What are the key statistics about prostate cancer? Retrieved from Cancer/ProstateCancer /DetailedGuide/prostate-cancer-key-statistics American Cancer Society. (2011). How is prostate cancer found? Retrieved from Gaziano, J. M., Glynn, R. J., Christen, W. G., Kurth, T., Belanger, C., MacFadyen, J.,... Buring, J. E. (2009). Vitamin E and C in the prevention of prostate and total cancer in men: The physicians’ health study II randomized controlled trial. Journal of the American Medical Association, 301(1), Gonzalgo, M. L., & Isaacs, W. B. (2003). Molecular pathways to prostate cancer. Journal of Urology, 170, 2444–52. Gropper, S. S., Smith, J. L., & Groff, J. L., (2009). The Fat-Soluble Vitamins. In P. Adams & A. Lustig (Eds.), Advanced nutrition and human metabolism (pp ). Belmont, CA: Wadsworth. Klein, E. A., Thompson Jr., I. M., Tangen, C.M., Crowley, J. J., Lucia, M. S., Goodman, P.J.,... Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association, 306(14), Lippman, S. M., Klein, E. A., Goodman, P. J., Lucia, M. S., Thompson, I. M., Ford, L. G.,... Coltman Jr., C. A. (2009). Effect of selenium and vitamin E on risk of prostate cancer and other cancers: The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association, 301(1), Massachusetts Medical Society (1994). The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers: The alpha-tocopherol, beta carotene cancer prevention study group. New England Journal of Medicine, 330(15),