This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Duffield-Lillico, A. J. Articles by Clark, L. C. Search for Related Content PubMed PubMed Citation Articles by Duffield-Lillico, A. J. Articles by Clark, L. C.

Baseline Characteristics and the Effect of Selenium Supplementation on Cancer Incidence in a Randomized Clinical Trial

A Summary Report of the Nutritional Prevention of Cancer Trial¹

Arizona Cancer Center [A. J. D-L., M. E. R., J. R. M., L. C. C.] and Arizona College of Public Health [M. E. R., J. R. M.], University of Arizona, Tucson, Arizona 85724; School of Operations Research and Industrial Engineering [B. W. T.] and Division of Nutritional Sciences [G. F. C.], Cornell University, Ithaca, New York 14853; School of Public Health, University of Texas-Houston Health Science Center, Dallas, Texas 75390 [L. A. F.]; and Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, South Carolina 29425 [E. H. S.]

The Nutritional Prevention of Cancer Trial was a randomized, clinical trial designed to evaluate the efficacy of selenium asselenized yeast (200 µg daily) in preventing therecurrence of nonmelanoma skin cancer among 1312 residents of the Eastern United States. Original secondary analyses through December 31, 1993 showed striking inverse associations between treatment and the incidence of total [hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.46–0.82], lung, prostate, and colorectal cancer and total cancer mortality. This report presents results through February 1, 1996, the end of blinded treatment. Effect modification by baseline characteristics is also evaluated. The effects of treatment overall and within subgroups of baseline age, gender, smoking status, and plasma selenium were examined using incidence rate ratios and Cox proportional hazards models. Selenium supplementation reduced total (HR = 0.75, 95% CI = 0.58–0.97) and prostate (HR = 0.48, 95% CI = 0.28–0.80) cancer incidence but was not significantly associated with lung (HR = 0.74, 95% CI = 0.44–1.24) and colorectal (HR = 0.46, 95% CI = 0.21–1.02) cancer incidence. The effects of treatment on other site-specific cancers are also described. The protective effect of selenium was confined to males (HR = 0.67, 95% CI = 0.50–0.89) and was most pronounced in former smokers. Participants with baseline plasma selenium concentrations in the lowest two tertiles (<121.6 ng/ml) experienced reductions in total cancer incidence, whereas those in the highest tertile showed an elevated incidence (HR = 1.20, 95% CI = 0.77–1.86). The Nutritional Prevention of Cancer trial continues to show a protective effect of selenium on cancer incidence, although not all site-specific cancers exhibited a reduction in incidence. This treatment effect was restricted to males and to those with lower baseline plasma selenium concentrations.

This article has been cited by other articles:

				U. Peters, N. Chatterjee, R. B. Hayes, R. E. Schoen, Y. Wang, S. J. Chanock, and C. B. Foster Variation in the Selenoenzyme Genes and Risk of Advanced Distal Colorectal Adenoma Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1144 - 1154. [Abstract] [Full Text] [PDF]

				J. Bleys, A. Navas-Acien, and E. Guallar Serum Selenium Levels and All-Cause, Cancer, and Cardiovascular Mortality Among US Adults Arch Intern Med, February 25, 2008; 168(4): 404 - 410. [Abstract] [Full Text] [PDF]

				S. Liu, H. Zhang, L. Zhu, L. Zhao, and Y. Dong Kruppel-Like Factor 4 Is a Novel Mediator of Selenium in Growth Inhibition Mol. Cancer Res., February 1, 2008; 6(2): 306 - 313. [Abstract] [Full Text] [PDF]

				D. Z. J. Chu, G. Gibson, D. David, and Y. Yen The Surgeon's Role in Cancer Prevention. The Model in Colorectal Carcinoma Ann. Surg. Oncol., November 1, 2007; 14(11): 3054 - 3069. [Abstract] [Full Text] [PDF]

				S. Hercberg, K. Ezzedine, C. Guinot, P. Preziosi, P. Galan, S. Bertrais, C. Estaquio, S. Briancon, A. Favier, J. Latreille, et al. Antioxidant Supplementation Increases the Risk of Skin Cancers in Women but Not in Men J. Nutr., September 1, 2007; 137(9): 2098 - 2105. [Abstract] [Full Text] [PDF]

				S. Stranges, J. R. Marshall, R. Natarajan, R. P. Donahue, M. Trevisan, G. F. Combs, F. P. Cappuccio, A. Ceriello, and M. E. Reid Effects of Long-Term Selenium Supplementation on the Incidence of Type 2 Diabetes: A Randomized Trial Ann Intern Med, August 21, 2007; 147(4): 217 - 223. [Abstract] [Full Text] [PDF]

				J. Bleys, A. Navas-Acien, and E. Guallar Selenium and Diabetes: More Bad News for Supplements Ann Intern Med, August 21, 2007; 147(4): 271 - 272. [Full Text] [PDF]

				Y. Cui, S. Vogt, N. Olson, A. G. Glass, and T. E. Rohan Levels of Zinc, Selenium, Calcium, and Iron in Benign Breast Tissue and Risk of Subsequent Breast Cancer Cancer Epidemiol. Biomarkers Prev., August 1, 2007; 16(8): 1682 - 1685. [Abstract] [Full Text] [PDF]

				T. M. Vogt, R. G. Ziegler, B. H. Patterson, and B. I. Graubard Racial Differences in Serum Selenium Concentration: Analysis of US Population Data from the Third National Health and Nutrition Examination Survey Am. J. Epidemiol., August 1, 2007; 166(3): 280 - 288. [Abstract] [Full Text] [PDF]

				E. de Vries, I. Soerjomataram, S. Houterman, M. W. J. Louwman, and J. W. W. Coebergh Decreased Risk of Prostate Cancer after Skin Cancer Diagnosis: A Protective Role of Ultraviolet Radiation? Am. J. Epidemiol., April 15, 2007; 165(8): 966 - 972. [Abstract] [Full Text] [PDF]

				U. Peters, C. B Foster, N. Chatterjee, A. Schatzkin, D. Reding, G. L Andriole, E D. Crawford, S. Sturup, S. J Chanock, and R. B Hayes Serum selenium and risk of prostate cancer--a nested case-control study Am. J. Clinical Nutrition, January 1, 2007; 85(1): 209 - 217. [Abstract] [Full Text] [PDF]

				P. Greenwald, D. Anderson, S. A Nelson, and P. R Taylor Clinical trials of vitamin and mineral supplements for cancer prevention Am. J. Clinical Nutrition, January 1, 2007; 85(1): 314S - 317S. [Abstract] [Full Text] [PDF]

				S. T. Mayne and B. Cartmel Chemoprevention of Second Cancers Cancer Epidemiol. Biomarkers Prev., November 1, 2006; 15(11): 2033 - 2037. [Abstract] [Full Text] [PDF]

				H. Okamoto, J. Li, A. O. Vortmeyer, H. Jaffe, Y.-S. Lee, S. Glasker, T.-S. Sohn, W. Zeng, B. Ikejiri, M. A. Proescholdt, et al. Comparative proteomic profiles of meningioma subtypes. Cancer Res., October 15, 2006; 66(20): 10199 - 10204. [Abstract] [Full Text] [PDF]

				L. H. Kushi, T. Byers, C. Doyle, E. V. Bandera, M. McCullough, T. Gansler, K. S. Andrews, M. J. Thun, and The American Cancer Society 2006 Nutrition and Phy American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention: Reducing the Risk of Cancer With Healthy Food Choices and Physical Activity CA Cancer J Clin, September 1, 2006; 56(5): 254 - 281. [Abstract] [Full Text] [PDF]

				J. R. Marshall, W. Sakr, D. Wood, D. Berry, C. Tangen, F. Parker, I. Thompson, S. M. Lippman, R. Lieberman, D. Alberts, et al. Design and Progress of a Trial of Selenium to Prevent Prostate Cancer among Men with High-Grade Prostatic Intraepithelial Neoplasia. Cancer Epidemiol. Biomarkers Prev., August 1, 2006; 15(8): 1479 - 1484. [Abstract] [Full Text] [PDF]

				A. A. Davies, G. Davey Smith, R. Harbord, G. E. Bekkering, J. A. C. Sterne, R. Beynon, and S. Thomas Nutritional interventions and outcome in patients with cancer or preinvasive lesions: systematic review. J Natl Cancer Inst, July 19, 2006; 98(14): 961 - 973. [Abstract] [Full Text] [PDF]

				K. El-Bayoumy, A. Das, B. Narayanan, N. Narayanan, E. S. Fiala, D. Desai, C. V. Rao, S. Amin, and R. Sinha Molecular targets of the chemopreventive agent 1,4-phenylenebis (methylene)-selenocyanate in human non-small cell lung cancer Carcinogenesis, July 1, 2006; 27(7): 1369 - 1376. [Abstract] [Full Text] [PDF]

				R. D. Semba, B. Bartali, J. Zhou, C. Blaum, C.-W. Ko, and L. P. Fried Low serum micronutrient concentrations predict frailty among older women living in the community. J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2006; 61(6): 594 - 599. [Abstract] [Full Text] [PDF]

				S. Stranges, J. R. Marshall, M. Trevisan, R. Natarajan, R. P. Donahue, G. F. Combs, E. Farinaro, L. C. Clark, and M. E. Reid Effects of Selenium Supplementation on Cardiovascular Disease Incidence and Mortality: Secondary Analyses in a Randomized Clinical Trial Am. J. Epidemiol., April 15, 2006; 163(8): 694 - 699. [Abstract] [Full Text] [PDF]

				J. Y. Chun, N. Nadiminty, S. O. Lee, S. A. Onate, W. Lou, and A. C. Gao Mechanisms of selenium down-regulation of androgen receptor signaling in prostate cancer. Mol. Cancer Ther., April 1, 2006; 5(4): 913 - 918. [Abstract] [Full Text] [PDF]

				U. Peters, N. Chatterjee, T. R. Church, C. Mayo, S. Sturup, C. B. Foster, A. Schatzkin, and R. B. Hayes High serum selenium and reduced risk of advanced colorectal adenoma in a colorectal cancer early detection program. Cancer Epidemiol. Biomarkers Prev., February 1, 2006; 15(2): 315 - 320. [Abstract] [Full Text] [PDF]

				M. A. NELSON, A.-C. GOULET, E. T. JACOBS, and P. LANCE Studies into the Anticancer Effects of Selenomethionine against Human Colon Cancer Ann. N.Y. Acad. Sci., November 1, 2005; 1059(1): 26 - 32. [Abstract] [Full Text] [PDF]

				P. G. Reeves, P. D. Leary, B. R. Gregoire, J. W. Finley, J. E. Lindlauf, and L. K. Johnson Selenium Bioavailability from Buckwheat Bran in Rats Fed a Modified AIN-93G Torula Yeast-Based Diet J. Nutr., November 1, 2005; 135(11): 2627 - 2633. [Abstract] [Full Text] [PDF]

				Y. M. Shah, M. Al-Dhaheri, Y. Dong, C. Ip, F. E. Jones, and B. G. Rowan Selenium disrupts estrogen receptor {alpha} signaling and potentiates tamoxifen antagonism in endometrial cancer cells and tamoxifen-resistant breast cancer cells Mol. Cancer Ther., August 1, 2005; 4(8): 1239 - 1249. [Abstract] [Full Text] [PDF]

				Y. Dong, H. Zhang, A. C. Gao, J. R. Marshall, and C. Ip Androgen receptor signaling intensity is a key factor in determining the sensitivity of prostate cancer cells to selenium inhibition of growth and cancer-specific biomarkers Mol. Cancer Ther., July 1, 2005; 4(7): 1047 - 1055. [Abstract] [Full Text] [PDF]

				D. J. Waters, S. Shen, L. T. Glickman, D. M. Cooley, D. G. Bostwick, J. Qian, G. F. Combs Jr, and J. S. Morris Prostate cancer risk and DNA damage: translational significance of selenium supplementation in a canine model Carcinogenesis, July 1, 2005; 26(7): 1256 - 1262. [Abstract] [Full Text] [PDF]

				J. W. FINLEY Proposed Criteria for Assessing the Efficacy of Cancer Reduction by Plant Foods Enriched in Carotenoids, Glucosinolates, Polyphenols and Selenocompounds Ann. Bot., June 1, 2005; 95(7): 1075 - 1096. [Abstract] [Full Text] [PDF]

				E. Kowalska, S. A. Narod, T. Huzarski, S. Zajaczek, J. Huzarska, B. Gorski, and J. Lubinski Increased Rates of Chromosome Breakage in BRCA1 Carriers Are Normalized by Oral Selenium Supplementation Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1302 - 1306. [Abstract] [Full Text] [PDF]

				H. Li, P. W. Kantoff, E. Giovannucci, M. F. Leitzmann, J. M. Gaziano, M. J. Stampfer, and J. Ma Manganese Superoxide Dismutase Polymorphism, Prediagnostic Antioxidant Status, and Risk of Clinical Significant Prostate Cancer Cancer Res., March 15, 2005; 65(6): 2498 - 2504. [Abstract] [Full Text] [PDF]

				G. F. Combs Jr Current Evidence and Research Needs to Support a Health Claim for Selenium and Cancer Prevention J. Nutr., February 1, 2005; 135(2): 343 - 347. [Abstract] [Full Text] [PDF]

				P. R. Taylor and P. Greenwald Nutritional Interventions in Cancer Prevention J. Clin. Oncol., January 10, 2005; 23(2): 333 - 345. [Abstract] [Full Text] [PDF]

				A. J. Duffield-Lillico, I. Shureiqi, and S. M. Lippman Can Selenium Prevent Colorectal Cancer? A Signpost From Epidemiology J Natl Cancer Inst, November 17, 2004; 96(22): 1645 - 1647. [Full Text] [PDF]

				E. T. Jacobs, R. Jiang, D. S. Alberts, E. R. Greenberg, E. W. Gunter, M. R. Karagas, E. Lanza, L. Ratnasinghe, M. E. Reid, A. Schatzkin, et al. Selenium and Colorectal Adenoma: Results of a Pooled Analysis J Natl Cancer Inst, November 17, 2004; 96(22): 1669 - 1675. [Abstract] [Full Text] [PDF]

				C. Jiang, H. Hu, B. Malewicz, Z. Wang, and J. Lu Selenite-induced p53 Ser-15 phosphorylation and caspase-mediated apoptosis in LNCaP human prostate cancer cells Mol. Cancer Ther., July 1, 2004; 3(7): 877 - 884. [Abstract] [Full Text] [PDF]

				H. Li, M. J. Stampfer, E. L. Giovannucci, J. S. Morris, W. C. Willett, J. M. Gaziano, and J. Ma A Prospective Study of Plasma Selenium Levels and Prostate Cancer Risk J Natl Cancer Inst, May 5, 2004; 96(9): 696 - 703. [Abstract] [Full Text] [PDF]

				H. Zhuo, A. H. Smith, and C. Steinmaus Selenium and Lung Cancer: A Quantitative Analysis of Heterogeneity in the Current Epidemiological Literature Cancer Epidemiol. Biomarkers Prev., May 1, 2004; 13(5): 771 - 778. [Abstract] [Full Text] [PDF]

				A.-S. Keck and J. W. Finley Cruciferous Vegetables: Cancer Protective Mechanisms of Glucosinolate Hydrolysis Products and Selenium Integr Cancer Ther, March 1, 2004; 3(1): 5 - 12. [Abstract] [PDF]

				H. Zhao, M. L. Whitfield, T. Xu, D. Botstein, and J. D. Brooks Diverse Effects of Methylseleninic Acid on the Transcriptional Program of Human Prostate Cancer Cells Mol. Biol. Cell, February 1, 2004; 15(2): 506 - 519. [Abstract] [Full Text] [PDF]

				W.-Q. Wei, C. C Abnet, Y.-L. Qiao, S. M Dawsey, Z.-W. Dong, X.-D. Sun, J.-H. Fan, E. W Gunter, P. R Taylor, and S. D Mark Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death Am. J. Clinical Nutrition, January 1, 2004; 79(1): 80 - 85. [Abstract] [Full Text] [PDF]

				A. J. Duffield-Lillico, E. H. Slate, M. E. Reid, B. W. Turnbull, P. A. Wilkins, G. F. Combs Jr., H. K. Park, E. G. Gross, G. F. Graham, M. S. Stratton, et al. Selenium Supplementation and Secondary Prevention of Nonmelanoma Skin Cancer in a Randomized Trial J Natl Cancer Inst, October 1, 2003; 95(19): 1477 - 1481. [Abstract] [Full Text] [PDF]

				P. A. van den Brandt, M. P. A. Zeegers, P. Bode, and R. A. Goldbohm Toenail Selenium Levels and the Subsequent Risk of Prostate Cancer: A Prospective Cohort Study Cancer Epidemiol. Biomarkers Prev., September 1, 2003; 12(9): 866 - 871. [Abstract] [Full Text] [PDF]

				E. Dewailly, G. Mulvad, H. S. Pedersen, J. C. Hansen, N. Behrendt, and J. P. H. Hansen Inuit Are Protected Against Prostate Cancer Cancer Epidemiol. Biomarkers Prev., September 1, 2003; 12(9): 926 - 927. [Abstract] [Full Text] [PDF]

				K. El-Bayoumy, B. A. Narayanan, D. H. Desai, N. K. Narayanan, B. Pittman, S. G. Amin, J. Schwartz, and D. W. Nixon Elucidation of molecular targets of mammary cancer chemoprevention in the rat by organoselenium compounds using cDNA microarray Carcinogenesis, September 1, 2003; 24(9): 1505 - 1514. [Abstract] [Full Text] [PDF]

				K. J. Hintze, K. A. Wald, H. Zeng, E. H. Jeffery, and J. W. Finley Thioredoxin Reductase in Human Hepatoma Cells Is Transcriptionally Regulated by Sulforaphane and Other Electrophiles via an Antioxidant Response Element- J. Nutr., September 1, 2003; 133(9): 2721 - 2727. [Abstract] [Full Text] [PDF]

				M. Vinceti, C. Malagoli, M. Bergomi, and G. Vivoli Correspondence re: Duffield-Lillico et al. Baseline Characteristics and the Effect of Selenium Supplementation on Cancer Incidence in a Randomized Clinical Trial: A Summary Report of the Nutritional Prevention of Cancer Trial. 11: 630-639, 2002 Cancer Epidemiol. Biomarkers Prev., January 1, 2003; 12(1): 77 - 77. [Full Text] [PDF]

				K. El-Bayoumy, J. P. Richie Jr., T. Boyiri, D. Komninou, B. Prokopczyk, N. Trushin, W. Kleinman, J. Cox, B. Pittman, and S. Colosimo Influence of Selenium-enriched Yeast Supplementation on Biomarkers of Oxidative Damage and Hormone Status in Healthy Adult Males: A Clinical Pilot Study Cancer Epidemiol. Biomarkers Prev., November 1, 2002; 11(11): 1459 - 1465. [Abstract] [Full Text] [PDF]