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, heartGropper, 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. 373-427). 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. 373-427). 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 http://www.cancer.org/Cancer/ProstateCancer /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 fromhttp://www.cancer.org/Cancer/ProstateCancer/OverviewGuide/prostate-

cancer- 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, 1549-1556

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), 1549-1556.

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 riskLippman, 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), 39-51.

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), 1549-1556.

Methods

• 427 sites in US, Canada, and Puerto Rico• Randomized between Aug. 2001-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), 1549-1556.

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), 1549-1556.

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 mgKlein, 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), 1549-1556.

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), 1549-1556.

Incidence of Prostate Cancer

Vitamin E Selenium Both Placebo480

500

520

540

560

580

600

620

640

To

tal

# o

f C

as

es

Incidence of Prostate CancerGroup Vitamin E Selenium Both Placebo Total

Cases 620 575 555 529 2279

P value .008 .18 .46

Hazard ratio

1.17 1.09 1.05

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), 1549-1556.

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), 1549-1556.

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 includedKlein, 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), 1549-1556.

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), 1029-1035.

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), 52-62.

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 http://www.cancer.org/

Cancer/ProstateCancer /DetailedGuide/prostate-cancer-key-statistics American Cancer Society. (2011). How is prostate cancer found? Retrieved from

http://www.cancer.org/Cancer/ProstateCancer/OverviewGuide/prostate-cancer-overview-diagnosed 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), 52-62. 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. 373-427). 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), 1549-1556. 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), 39-51.

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), 1029-1035.