Opportunities for Prevention
Chemoprevention with selenium and vitamin E
The effects of selenium and vitamin E, alone or in combination, on the risk of prostate cancer were studied in the Selenium and Vitamin E Cancer Prevention Trial (SELECT [NCT00006392]).[22,23,24] SELECT was a randomized, placebo-controlled trial of selenium (200 �g/d from L-selenomethionine), vitamin E (400 IU/d of all rac-[alpha]-tocopheryl acetate), or both (planned follow-up for a minimum of 7 years and a maximum of 12 years) for prostate cancer prevention. The primary endpoint was prostate cancer incidence as determined by routine clinical management.
Neither 200 �g of L-selenomethionine nor 400 IU of synthetic DL-(alpha)-tocopherol given orally, alone or combined, for a median of 5.5 years had significant effects on the primary or secondary endpoints. A statistically nonsignificant increased incidence of prostate cancer was observed in the vitamin E group (473 cases; hazard ratio = 1.13; 99% CI = 0.95-1.35; P = .06) compared with the placebo group (416 cases).
Chemoprevention with lycopene
Evidence exists that a diet with a high intake of fruits and vegetables is associated with a lower risk of cancer. Which, if any, micronutrients may account for this reduction is unknown. One group of nutrients often postulated as having chemoprevention properties is the carotenoids. Lycopene is the predominant circulating carotenoid in Americans and has a number of potential activities, including an antioxidant effect. It is encountered in a number of vegetables, most notably tomatoes, and is best absorbed if these products are cooked and in the presence of dietary fats or oils.
The earliest studies of the association of lycopene and prostate cancer risk were generally negative before 1995 with only one study of 180 case-control patients showing a reduced risk.[26,27,28,29] In 1995, an analysis of the Physicians' Health Study found a one-third reduction in prostate cancer risk in the group of men with the highest consumption of tomato products when compared with the group with the lowest level of consumption, which was attributed to the lycopene content of these vegetables. This large analysis prompted several subsequent studies, the results of which were mixed.[31,32] A review of the published data concluded that the evidence is weak that lycopene is associated with a reduced risk because previous studies were not controlled for total vegetable intake (i.e., separating the effect of tomatoes from vegetables), dietary intake instruments are poorly able to quantify lycopene intake, and other potential biases. Specific dietary supplementation with lycopene remains to be demonstrated to reduce prostate cancer risk.
- Thompson IM, Goodman PJ, Tangen CM, et al.: The influence of finasteride on the development of prostate cancer. N Engl J Med 349 (3): 215-24, 2003.
- Thompson IM, Klein EA, Lippman SM, et al.: Prevention of prostate cancer with finasteride: US/European perspective. Eur Urol 44 (6): 650-5, 2003.
- Andriole G, Bostwick D, Civantos F, et al.: The effects of 5alpha-reductase inhibitors on the natural history, detection and grading of prostate cancer: current state of knowledge. J Urol 174 (6): 2098-104, 2005.
- Etzioni RD, Howlader N, Shaw PA, et al.: Long-term effects of finasteride on prostate specific antigen levels: results from the prostate cancer prevention trial. J Urol 174 (3): 877-81, 2005.
- Kaplan SA, Roehrborn CG, Meehan AG, et al.: PCPT: Evidence that finasteride reduces risk of most frequently detected intermediate- and high-grade (Gleason score 6 and 7) cancer. Urology 73 (5): 935-9, 2009.
- Andriole GL, Bostwick DG, Brawley OW, et al.: Effect of dutasteride on the risk of prostate cancer. N Engl J Med 362 (13): 1192-202, 2010.
- Thompson I, Feigl P, Coltman C: Chemoprevention of prostate cancer with finasteride. Important Adv Oncol : 57-76, 1995.
- Nelson PS, Gleason TP, Brawer MK: Chemoprevention for prostatic intraepithelial neoplasia. Eur Urol 30 (2): 269-78, 1996.
- Kolonel LN, Hankin JH, Whittemore AS, et al.: Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study. Cancer Epidemiol Biomarkers Prev 9 (8): 795-804, 2000.
- Key TJ, Allen N, Appleby P, et al.: Fruits and vegetables and prostate cancer: no association among 1104 cases in a prospective study of 130544 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 109 (1): 119-24, 2004 Mar10.
- Shike M, Latkany L, Riedel E, et al.: Lack of effect of a low-fat, high-fruit, -vegetable, and -fiber diet on serum prostate-specific antigen of men without prostate cancer: results from a randomized trial. J Clin Oncol 20 (17): 3592-8, 2002.
- Heby O: Role of polyamines in the control of cell proliferation and differentiation. Differentiation 19 (1): 1-20, 1981.
- Danzin C, Jung MJ, Grove J, et al.: Effect of alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, on polyamine levels in rat tissues. Life Sci 24 (6): 519-24, 1979.
- Metcalf BW, Bey P, Danzin C, et al.: Catalytic irreversible inhibition of mammalian ornithine decarboxylase (E.C. 18.104.22.168) by substrate and product analogues. J Am Chem Soc 100(8): 2551-2553, 1978.
- Heston WD, Kadmon D, Lazan DW, et al.: Copenhagen rat prostatic tumor ornithine decarboxylase activity (ODC) and the effect of the ODC inhibitor alpha-difluoromethylornithine. Prostate 3 (4): 383-9, 1982.
- Abeloff MD, Slavik M, Luk GD, et al.: Phase I trial and pharmacokinetic studies of alpha-difluoromethylornithine--an inhibitor of polyamine biosynthesis. J Clin Oncol 2 (2): 124-30, 1984.
- Schwartz GG, Hulka BS: Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). Anticancer Res 10 (5A): 1307-11, 1990 Sep-Oct.
- Eisman JA, Barkla DH, Tutton PJ: Suppression of in vivo growth of human cancer solid tumor xenografts by 1,25-dihydroxyvitamin D3. Cancer Res 47 (1): 21-5, 1987.
- Chida K, Hashiba H, Fukushima M, et al.: Inhibition of tumor promotion in mouse skin by 1 alpha,25-dihydroxyvitamin D3. Cancer Res 45 (11 Pt 1): 5426-30, 1985.
- Adlercreutz H, Markkanen H, Watanabe S: Plasma concentrations of phyto-oestrogens in Japanese men. Lancet 342 (8881): 1209-10, 1993.
- Peterson G, Barnes S: Genistein and biochanin A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation. Prostate 22 (4): 335-45, 1993.
- Lippman SM, Klein EA, Goodman PJ, 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). JAMA 301 (1): 39-51, 2009.
- Gann PH: Randomized trials of antioxidant supplementation for cancer prevention: first bias, now chance--next, cause. JAMA 301 (1): 102-3, 2009.
- Gaziano JM, Glynn RJ, Christen WG, et al.: Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA 301 (1): 52-62, 2009.
- Gerster H: The potential role of lycopene for human health. J Am Coll Nutr 16 (2): 109-26, 1997.
- Hsing AW, Comstock GW, Abbey H, et al.: Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer. J Natl Cancer Inst 82 (11): 941-6, 1990.
- Mills PK, Beeson WL, Phillips RL, et al.: Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer 64 (3): 598-604, 1989.
- Schuman LM, Mandel JS, Radke A, et al.: Some selected features of the epidemiology of prostatic cancer: Minneapolis-St. Paul, Minnesota case-control study, 1976-1979. [Abstract] Trends in Cancer Incidence: Causes and Practical Implications (Proceedings of a Symposium Held in Oslo, Norway, Aug. 6-7, 1980) pp 345-354.
- Le Marchand L, Hankin JH, Kolonel LN, et al.: Vegetable and fruit consumption in relation to prostate cancer risk in Hawaii: a reevaluation of the effect of dietary beta-carotene. Am J Epidemiol 133 (3): 215-9, 1991.
- Giovannucci E, Ascherio A, Rimm EB, et al.: Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 87 (23): 1767-76, 1995.
- Jain MG, Hislop GT, Howe GR, et al.: Plant foods, antioxidants, and prostate cancer risk: findings from case-control studies in Canada. Nutr Cancer 34 (2): 173-84, 1999.
- Key TJ, Silcocks PB, Davey GK, et al.: A case-control study of diet and prostate cancer. Br J Cancer 76 (5): 678-87, 1997.
- Kristal AR, Cohen JH: Invited commentary: tomatoes, lycopene, and prostate cancer. How strong is the evidence? Am J Epidemiol 151 (2): 124-7; discussion 128-30, 2000.