Plasma Tocopherols and Risk of Prostate Cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed higher prostate cancer incidence in men supplemented with high-dose α-tocopherol. We, therefore, examined whether presupplementation plasma α-tocopherol or γ-tocopherol was associated with overall or high-grade prostate cancer. A stratified case–cohort sample that included 1,746 incident prostate cancer cases diagnosed through June 2009 and a subcohort of 3,211 men was derived from the SELECT trial of 35,533 men. Plasma was collected at entry from 2001 to 2004, and median follow-up was 5.5 years (range, 0–7.9 years). Incidence of prostate cancer as a function of plasma α-tocopherol, γ-tocopherol, and supplementation with α-tocopherol or selenomethionine was estimated by the hazard ratio (HR). Plasma γ-tocopherol was not associated with prostate cancer. Men with higher α-tocopherol concentrations seemed to have risk similar to that of men with lower concentrations [overall HR for fifth (Q5) vs. first quintile (Q1), 1.21; 95 % confidence interval (CI), 0.88–1.66; P-trend = 0.24; in the trial placebo arm, Q5 HR, 0.85; 95% CI, 0.44–1.62; P-trend = 0.66]. We found a strong positive plasma α-tocopherol association among men receiving the trial selenomethionine supplement [Q5 HR, 2.04; 95% CI, 1.29–3.22; P-trend = 0.005]. A positive plasma α-tocopherol–prostate cancer association also seemed limited to high-grade disease (Gleason grade, 7–10; overall Q5 HR, 1.59; 95% CI, 1.13–2.24; P-trend = 0.001; among men receiving selenomethionine, Q5 HR, 2.12; 95% CI, 1.32–3.40; P-trend = 0.0002). Our findings indicate that higher plasma α-tocopherol concentrations may interact with selenomethionine supplements to increase high-grade prostate cancer risk, suggesting a biologic interaction between α-tocopherol and selenium itself or selenomethionine. Cancer Prev Res; 7(9); 886–95. ©2014 AACR.

[1]  J. Crowley,et al.  Moving a randomized clinical trial into an observational cohort , 2013, Clinical trials.

[2]  R. Hayes,et al.  Serum α-Tocopherol and γ-Tocopherol Concentrations and Prostate Cancer Risk in the PLCO Screening Trial: A Nested Case-Control Study , 2012, PloS one.

[3]  K. Birkner,et al.  The influence of vitamin E and methionine on the activity of enzymes and the morphological picture of liver of rats intoxicated with sodium fluoride. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[4]  C. Lawton,et al.  Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) , 2012 .

[5]  A. Kristal,et al.  Genetic variation in myeloperoxidase modifies the association of serum α-tocopherol with aggressive prostate cancer among current smokers. , 2011, The Journal of nutrition.

[6]  P. Clark,et al.  Serum Methionine Metabolites Are Risk Factors for Metastatic Prostate Cancer Progression , 2011, PloS one.

[7]  S. Chanock,et al.  Genome-wide association study identifies common variants associated with circulating vitamin E levels , 2011, Human molecular genetics.

[8]  I. Thompson,et al.  Serum phospholipid fatty acids and prostate cancer risk: results from the prostate cancer prevention trial. , 2011, American journal of epidemiology.

[9]  I. Thompson,et al.  Serum Lycopene Concentration and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial , 2011, Cancer Epidemiology, Biomarkers & Prevention.

[10]  Joseph M. Betz,et al.  Dietary supplement use in the United States, 2003-2006. , 2011, The Journal of nutrition.

[11]  L. Klotz,et al.  Diet and prostate cancer: mechanisms of action and implications for chemoprevention , 2010, Nature Reviews Urology.

[12]  M. Gail,et al.  Associations between alpha-tocopherol, beta-carotene, and retinol and prostate cancer survival. , 2009, Cancer research.

[13]  Satoru Takahashi,et al.  Suppression of prostate cancer in a transgenic rat model via γ‐tocopherol activation of caspase signaling , 2009, The Prostate.

[14]  B. Henderson,et al.  Association of selenium, tocopherols, carotenoids, retinol, and 15-isoprostane F2t in serum or urine with prostate cancer risk: the multiethnic cohort , 2009, Cancer Causes & Control.

[15]  J. Crowley,et al.  Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). , 2009, JAMA.

[16]  J. Manson,et al.  Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. , 2009, JAMA.

[17]  F. Berrino,et al.  Plasma carotenoids, retinol, and tocopherols and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition study. , 2007, The American journal of clinical nutrition.

[18]  Karla A. Lawson,et al.  Serum and Dietary Vitamin E in Relation to Prostate Cancer Risk , 2007, Cancer Epidemiology Biomarkers & Prevention.

[19]  N. Mills,et al.  Alpha-tocopheryl succinate (α-TOS) modulates human prostate LNCaP xenograft growth and gene expression in BALB/c nude mice fed two levels of dietary soybean oil , 2007, European journal of nutrition.

[20]  A. Mokdad,et al.  Distribution of serum concentrations of alpha-tocopherol and gamma-tocopherol in the US population. , 2006, The American journal of clinical nutrition.

[21]  A. Mokdad,et al.  Distribution of serum concentrations of α-tocopherol and γ-tocopherol in the US population , 2006 .

[22]  R. Schindler,et al.  Flavonoids and vitamin E reduce the release of the angiogenic peptide vascular endothelial growth factor from human tumor cells. , 2006, The Journal of nutrition.

[23]  D. Albanes,et al.  Serum α-Tocopherol and γ-Tocopherol in Relation to Prostate Cancer Risk in a Prospective Study , 2005 .

[24]  Michael M Lieber,et al.  Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). , 2005, Journal of the National Cancer Institute.

[25]  D. Albanes,et al.  Serum alpha-tocopherol and gamma-tocopherol in relation to prostate cancer risk in a prospective study. , 2005, Journal of the National Cancer Institute.

[26]  L. Klotz,et al.  Synergistic effect of vitamin E and selenium in human prostate cancer cell lines , 2004, Prostate Cancer and Prostatic Diseases.

[27]  J. Crowley,et al.  Molecular epidemiologic studies within the Selenium and Vitamin E Cancer Prevention Trial (SELECT) , 2004, Cancer Causes & Control.

[28]  C. Ip,et al.  Synergy between selenium and vitamin E in apoptosis induction is associated with activation of distinctive initiator caspases in human prostate cancer cells. , 2003, Cancer research.

[29]  Nea Malila,et al.  Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. , 2003, JAMA.

[30]  G. Omenn,et al.  The association between lung and prostate cancer risk, and serum micronutrients: results and lessons learned from beta-carotene and retinol efficacy trial. , 2003, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[31]  A. Alberg,et al.  Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer. , 2003, American journal of epidemiology.

[32]  N. Fleshner.  Vitamin E and prostate cancer. , 2002, The Urologic clinics of North America.

[33]  A. Azzi,et al.  Vitamin E: protective role of a Janus molecule , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[34]  D. Albanes,et al.  Effects of long‐term α‐tocopherol supplementation on serum hormones in older men * , 2001 .

[35]  D. Albanes,et al.  Effects of long-term alpha-tocopherol supplementation on serum hormones in older men. , 2001, The Prostate.

[36]  J. S. Morris,et al.  Association Between α-Tocopherol, γ-Tocopherol, Selenium, and Subsequent Prostate Cancer , 2000 .

[37]  J. S. Morris,et al.  Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. , 2000, Journal of the National Cancer Institute.

[38]  W E Barlow,et al.  Analysis of case-cohort designs. , 1999, Journal of clinical epidemiology.

[39]  E. Rimm,et al.  Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[40]  W. Willett,et al.  Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. , 1999, Cancer research.

[41]  S. Ripatti,et al.  Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. , 1998, Journal of the National Cancer Institute.

[42]  G. Stemmermann,et al.  Serum micronutrients and prostate cancer in Japanese Americans in Hawaii. , 1997, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[43]  M. Eichholzer,et al.  Prediction of male cancer mortality by plasma levels of interacting vitamins: 17‐year follow‐up of the prospective Basel study , 1996, International journal of cancer.

[44]  W. Barlow,et al.  Robust variance estimation for the case-cohort design. , 1994, Biometrics.

[45]  Z. Ying,et al.  Checking the Cox model with cumulative sums of martingale-based residuals , 1993 .

[46]  R. Hayes,et al.  Serum retinal and prostate cancer , 1988 .

[47]  R. Hayes,et al.  Serum retinol and prostate cancer. , 1988, Cancer.

[48]  R. Peto,et al.  Serum vitamin E and risk of cancer among Finnish men during a 10-year follow-up. , 1988, American journal of epidemiology.