Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Effects of Selenium Supplementation for Cancer Prevention in Patients With Carcinoma of the Skin: A Randomized Controlled Trial

Effects of Selenium Supplementation for Cancer Prevention in Patients With Carcinoma of the Skin:... Abstract Objective. —To determine whether a nutritional supplement of selenium will decrease the incidence of cancer. Design. —A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial. Setting. —Seven dermatology clinics in the eastern United States. Patients. —A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years. Interventions. —Oral administration of 200 μg of selenium per day or placebo. Main Outcome Measures. —The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers. Results. —After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR, 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred. Conclusions. —Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made. References 1. Shamberger RJ, Frost DV. Possible protective effect of selenium against human cancer . Can Med Assoc J . 1969;100:682. 2. Shamberger RJ, Willis CE. Selenium distribution of human cancer mortality . Crit Rev Clin Lab Sci . 1971;2:211-221.Crossref 3. Schrauzer GN, Thead WJ. Interpretation of the methylene blue reduction test of human plasma and the possible cancer protecting effect of selenium . Experientia . 1971;27:1069-1071.Crossref 4. Combs GF Jr, Combs S. The Role of Selenium in Nutrition . New York, NY: Academic Press; 1986. 5. Burk RF, Hill KE. Regulation of selenoproteins . Annu Rev Nutr . 1993;13:65-81.Crossref 6. Combs GF Jr. Essentiality and toxicity of selenium: a critique of the recommended dietary allowance and the reference dose . In: Mertz W, Abernathy CO, Olin SS, eds. Risk Assessment of Essential Elements . Washington, DC: ILSI Press; 1994:167-183. 7. Subcommittee on the Tenth Edition of the RDAs, Food and Nutrition Board, Commission on Life Sciences, National Research Council. Recommended Dietary Allowances , Tenth Edition . Washington, DC: National Academy Press; 1989. 8. Combs GF Jr. Selenium and cancer . In: Wang Z, ed. Biochemistry and Molecular Biology of Selenium . Beijing, China: Chinese Academy of Science; 1995. 9. Milner JA. Effect of selenium on virally induced and transplantable tumor models . Fed Proc . 1985; 44:2568-2572. 10. Ip C. The chemopreventive role of selenium in carcinogenesis . J Am Coll Toxicol . 1986;5:7-20Crossref 11. Ip C, Medina D. Current concept of selenium and mammary tumorigenesis . In: Medina D, Kidwell W, Heppner G, Anderson EP, eds. Cellular and Molecular Biology of Breast Cancer . New York, NY: Plenum Press; 1987:479. 12. El-Bayoumy K. The role of selenium in cancer prevention . In: De Vita VT, Hellman S, Rosenberg SS, eds. Practice of Oncology . 4th ed. Philadelphia, Pa: JB Lippincott; 1991:1-15. 13. Schrauzer GN, White DA, Schneider CJ. Cancer mortality correlation studies, III . Bioinorganic Chem . 1977;7:23-34.Crossref 14. Clark LC, Cantor KP, Allaway WH. Selenium in forage crops and cancer mortality in US counties . Arch Environ Health . 1991;46:37-42.Crossref 15. Clark LC. The epidemiology of selenium and cancer . Fed Proc . 1985;44:2584-2590. 16. Salonen JT, Alfthan G, Huttunen JK, Puska P. Association between serum selenium and the risk of cancer . Am J Epidemiol . 1984;120:342-349. 17. Salonen JT, Salonen R, Lappeteläinen R, Mäenpää PH, Alfthan G, Puska P. Risk of cancer in relation to serum concentrations of selenium and vitamins A and E . BMJ . 1985;290:417-420.Crossref 18. Willett W, Polk B, Morris S, et al. Prediagnostic serum selenium and risk of cancer . Lancet . 1983;2:130-134.Crossref 19. Kok FJ, De Bruijn AM, Hofman A, Vermeeren R, Valkenburg HA. Is serum selenium a risk factor for cancer in men only? Am J Epidemiol . 1987;125:12-16. 20. Virtamo J, Valkeila E, Alfthan G, Punsar S, Huttunen JK, Karvonen MJ. Serum selenium and risk of cancer . Cancer . 1987;60:145-148.Crossref 21. van den Brandt P, Goldbohm R, van't Veer P, et al. A prospective cohort study of toenail selenium levels and risk of gastrointestinal cancer . J Natl Cancer Inst . 1993;85:224-229.Crossref 22. Peleg I, Morris S, Hames CG. Is serum selenium a risk factor for cancer? Med Oncol Tumor Pharmacother . 1985;2:157-163. 23. Knekt P, Aromaa A, Maatela J, et al. Serum selenium and subsequent risk of cancer among Finnish men and women . J Natl Cancer Inst . 1990;82:864-868.Crossref 24. Glattre E, Thomassen Y, Thoresen SO, et al. Prediagnostic serum selenium in a case-control study of thyroid cancer . Int J Epidemiol . 1989;18:45-49.Crossref 25. Fex G, Pettersson B, Akesson B. Low plasma selenium as a risk factor for cancer death in middleaged men . Nutr Cancer . 1987;10:221-229.Crossref 26. Menkes MS, Comstock GW, Vuilleumier JP, Helsing KJ, Rider AA, Brookmeyer RP. Serum betacarotene, vitamins A and E, selenium, and the risk of lung cancer . N Engl J Med . 1986;315:1250-1254.Crossref 27. Garland M, Morris JS, Stampfer MJ, et al. Prospective study of toenail selenium and cancer among women . J Natl Cancer Inst . 1995;87:497-505.Crossref 28. Schober SE, Comstock GW, Helsing KJ, et al. Serologic precursors of cancer . Am J Epidemiol . 1987;126:1033-1041. 29. Nomura A, Heilbrun LK, Morris JS, Stemmermann GN. Serum selenium and the risk of cancer, by specific sites . J Natl Cancer Inst . 1987;79:103-108. 30. Knekt P, Aromaa A, Maatela J, et al. Serum vitamin E, serum selenium and the risk of gastrointestinal cancer . Int J Cancer . 1988;42:846-850.Crossref 31. Ringstad J, Jacobsen BK, Tretli S, Thomassen Y. Serum selenium concentration associated with risk of cancer . J Clin Pathol . 1988;41:454-457.Crossref 32. Coates RJ, Weiss NS, Daling JR, Morris JS, Labbe RF. Serum levels of selenium and retinol and the subsequent risk of cancer . Am J Epidemiol . 1988; 128:515-523. 33. Clark LC, Graham GF, Crouse RG, Grimson R, Hulka B, Shy CM. Plasma selenium and skin neoplasms . Nutr Cancer . 1984;6:13-21.Crossref 34. Clark LC, Graham GF, Turnbull BW, Bray J, Hulka B, Shy CM. Non-melanoma skin cancer and plasma selenium: a prospective cohort study . In: Combs GF Jr, Spallholz JE, Levander OA, Oldfield JE, eds. The Third International Symposium on Selenium in Biology and Medicine . Westport, Conn: AVI Publishing Co; 1986:1122-1135. 35. Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China . J Natl Cancer Inst . 1993;85:1483-1492.Crossref 36. Li JY, Taylor PR, Li B. Nutrition intervention trials in Linxian, China . J Natl Cancer Inst . 1993; 85:1492-1498.Crossref 37. Olson OE, Palmer IS, Cary EE. Modification of the official fluorometric method for selenium in plants . J Assoc Off Anal Chem . 1975;58:117-126. 38. McShane LM, Clark LC, Combs GF Jr, Turnbull BW. Reporting the accuracy of biochemical measurements for epidemiologic and nutrition studies . Am J Clin Nutr . 1991;53:1354-1360. 39. Abu-Libdeh H, Turnbull BW, Clark LC. Analysis of multi-type recurrent events in longitudinal studies . Biometrics . 1990;46:1017-1023.Crossref 40. Luo X, Turnbull BW, Cai H, Clark LC. Regression for censored survival data with lag effects . Commun Stat . 1994;23:3417-3438.Crossref 41. Allaway WH, Kubota J, Losee F, Roth M. Selenium, molybdenum and vanadium in human blood . Arch Environ Health . 1968;16:342-348.Crossref 42. National Cancer Institute, State Cancer Control and Data Program. Cancer Mortality by Pentad 1953-1957 to 1983-1987 . Bethesda, Md: National Institutes of Health; 1992. 43. Nelson MA, Einspahr JG, Alberts DS, et al. Analysis of the p53 gene in human precancerous actinic keratosis lesions and squamous cell cancers . Cancer Lett . 1994;85:23-29.Crossref 44. Gailani MR, Leffell DJ, Ziegler A, Gross EG, Brash DE, Bale AE. Relationship between sunlight exposure and a key genetic alteration in basal cell carcinoma . J Natl Cancer Inst . 1996;88:349-354.Crossref 45. Lanfear J, Fleming J, Wu L, Webster G, Harrison PR. The selenium metabolite selenodiglutathione induces p53 and apoptosis . Carcinogenesis . 1994; 15:1378-1392.Crossref 46. Yang GQ, Yin S, Zhou R. Studies of safe maximal daily dietary Se-intake in a seleniferous area of China . J Trace Elem Electrolytes Health Dis . 1989;3:123-130. 47. Thompson JH, Wilson A, Lu J, et al. Comparison of the effects of an organic and inorganic form of selenium on a mammary carcinoma cell line . Carcinogenesis . 1994;15:183-186.Crossref 48. Pahor M, Gurainik JM, Ferrucci L, et al. Calcium channel blockade and incidence of cancer in aged populations . Lancet . 1996;348:493-497.Crossref 49. The LRC Study Group. The Lipid Research Clinics Coronary Primary Prevention Trial results . JAMA . 1984;251:351-364.Crossref 50. Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia . N Engl J Med . 1987;317:1237-1245.Crossref 51. Comstock GW, Bush TL, Helzlsouer K. Serum retinol, beta-carotene, vitamin E and selenium as related to subsequent cancer of specific sites . Am J Epidemiol . 1992;135:115-121. 52. Pocock SJ, Geller NL, Tsiatis AA. The analysis of multiple endpoints in clinical trials . Biometrics . 1987;43:487-498.Crossref 53. Rothman KJ. No adjustments are needed for multiple comparisons . Epidemiology . 1990;1:43-46.Crossref 54. Tannock IF. False-positive results in clinical trials . J Natl Cancer Inst . 1996;88:206-207.Crossref 55. Cook RJ, Farewell VT. Multiplicity considerations in the design and analysis of clinical trials . J R Stat Soc A . 1996;159:93-110.Crossref 56. Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient, I: introduction and design . Br J Cancer . 1976;34:585-612.Crossref 57. Cox DR. In Discussion: Jennison C, Turnbull BW. Interim analyses . J R Stat Soc B . 1989;51:338. 58. Jennison C, Turnbull BW. Interim analyses . J R Stat Soc B . 1989;51:305-361. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Loading next page...
 
/lp/american-medical-association/effects-of-selenium-supplementation-for-cancer-prevention-in-patients-BRQpGi9JFM

References (74)

Publisher
American Medical Association
Copyright
Copyright © 1996 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.1996.03540240035027
Publisher site
See Article on Publisher Site

Abstract

Abstract Objective. —To determine whether a nutritional supplement of selenium will decrease the incidence of cancer. Design. —A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial. Setting. —Seven dermatology clinics in the eastern United States. Patients. —A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years. Interventions. —Oral administration of 200 μg of selenium per day or placebo. Main Outcome Measures. —The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers. Results. —After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR, 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred. Conclusions. —Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made. References 1. Shamberger RJ, Frost DV. Possible protective effect of selenium against human cancer . Can Med Assoc J . 1969;100:682. 2. Shamberger RJ, Willis CE. Selenium distribution of human cancer mortality . Crit Rev Clin Lab Sci . 1971;2:211-221.Crossref 3. Schrauzer GN, Thead WJ. Interpretation of the methylene blue reduction test of human plasma and the possible cancer protecting effect of selenium . Experientia . 1971;27:1069-1071.Crossref 4. Combs GF Jr, Combs S. The Role of Selenium in Nutrition . New York, NY: Academic Press; 1986. 5. Burk RF, Hill KE. Regulation of selenoproteins . Annu Rev Nutr . 1993;13:65-81.Crossref 6. Combs GF Jr. Essentiality and toxicity of selenium: a critique of the recommended dietary allowance and the reference dose . In: Mertz W, Abernathy CO, Olin SS, eds. Risk Assessment of Essential Elements . Washington, DC: ILSI Press; 1994:167-183. 7. Subcommittee on the Tenth Edition of the RDAs, Food and Nutrition Board, Commission on Life Sciences, National Research Council. Recommended Dietary Allowances , Tenth Edition . Washington, DC: National Academy Press; 1989. 8. Combs GF Jr. Selenium and cancer . In: Wang Z, ed. Biochemistry and Molecular Biology of Selenium . Beijing, China: Chinese Academy of Science; 1995. 9. Milner JA. Effect of selenium on virally induced and transplantable tumor models . Fed Proc . 1985; 44:2568-2572. 10. Ip C. The chemopreventive role of selenium in carcinogenesis . J Am Coll Toxicol . 1986;5:7-20Crossref 11. Ip C, Medina D. Current concept of selenium and mammary tumorigenesis . In: Medina D, Kidwell W, Heppner G, Anderson EP, eds. Cellular and Molecular Biology of Breast Cancer . New York, NY: Plenum Press; 1987:479. 12. El-Bayoumy K. The role of selenium in cancer prevention . In: De Vita VT, Hellman S, Rosenberg SS, eds. Practice of Oncology . 4th ed. Philadelphia, Pa: JB Lippincott; 1991:1-15. 13. Schrauzer GN, White DA, Schneider CJ. Cancer mortality correlation studies, III . Bioinorganic Chem . 1977;7:23-34.Crossref 14. Clark LC, Cantor KP, Allaway WH. Selenium in forage crops and cancer mortality in US counties . Arch Environ Health . 1991;46:37-42.Crossref 15. Clark LC. The epidemiology of selenium and cancer . Fed Proc . 1985;44:2584-2590. 16. Salonen JT, Alfthan G, Huttunen JK, Puska P. Association between serum selenium and the risk of cancer . Am J Epidemiol . 1984;120:342-349. 17. Salonen JT, Salonen R, Lappeteläinen R, Mäenpää PH, Alfthan G, Puska P. Risk of cancer in relation to serum concentrations of selenium and vitamins A and E . BMJ . 1985;290:417-420.Crossref 18. Willett W, Polk B, Morris S, et al. Prediagnostic serum selenium and risk of cancer . Lancet . 1983;2:130-134.Crossref 19. Kok FJ, De Bruijn AM, Hofman A, Vermeeren R, Valkenburg HA. Is serum selenium a risk factor for cancer in men only? Am J Epidemiol . 1987;125:12-16. 20. Virtamo J, Valkeila E, Alfthan G, Punsar S, Huttunen JK, Karvonen MJ. Serum selenium and risk of cancer . Cancer . 1987;60:145-148.Crossref 21. van den Brandt P, Goldbohm R, van't Veer P, et al. A prospective cohort study of toenail selenium levels and risk of gastrointestinal cancer . J Natl Cancer Inst . 1993;85:224-229.Crossref 22. Peleg I, Morris S, Hames CG. Is serum selenium a risk factor for cancer? Med Oncol Tumor Pharmacother . 1985;2:157-163. 23. Knekt P, Aromaa A, Maatela J, et al. Serum selenium and subsequent risk of cancer among Finnish men and women . J Natl Cancer Inst . 1990;82:864-868.Crossref 24. Glattre E, Thomassen Y, Thoresen SO, et al. Prediagnostic serum selenium in a case-control study of thyroid cancer . Int J Epidemiol . 1989;18:45-49.Crossref 25. Fex G, Pettersson B, Akesson B. Low plasma selenium as a risk factor for cancer death in middleaged men . Nutr Cancer . 1987;10:221-229.Crossref 26. Menkes MS, Comstock GW, Vuilleumier JP, Helsing KJ, Rider AA, Brookmeyer RP. Serum betacarotene, vitamins A and E, selenium, and the risk of lung cancer . N Engl J Med . 1986;315:1250-1254.Crossref 27. Garland M, Morris JS, Stampfer MJ, et al. Prospective study of toenail selenium and cancer among women . J Natl Cancer Inst . 1995;87:497-505.Crossref 28. Schober SE, Comstock GW, Helsing KJ, et al. Serologic precursors of cancer . Am J Epidemiol . 1987;126:1033-1041. 29. Nomura A, Heilbrun LK, Morris JS, Stemmermann GN. Serum selenium and the risk of cancer, by specific sites . J Natl Cancer Inst . 1987;79:103-108. 30. Knekt P, Aromaa A, Maatela J, et al. Serum vitamin E, serum selenium and the risk of gastrointestinal cancer . Int J Cancer . 1988;42:846-850.Crossref 31. Ringstad J, Jacobsen BK, Tretli S, Thomassen Y. Serum selenium concentration associated with risk of cancer . J Clin Pathol . 1988;41:454-457.Crossref 32. Coates RJ, Weiss NS, Daling JR, Morris JS, Labbe RF. Serum levels of selenium and retinol and the subsequent risk of cancer . Am J Epidemiol . 1988; 128:515-523. 33. Clark LC, Graham GF, Crouse RG, Grimson R, Hulka B, Shy CM. Plasma selenium and skin neoplasms . Nutr Cancer . 1984;6:13-21.Crossref 34. Clark LC, Graham GF, Turnbull BW, Bray J, Hulka B, Shy CM. Non-melanoma skin cancer and plasma selenium: a prospective cohort study . In: Combs GF Jr, Spallholz JE, Levander OA, Oldfield JE, eds. The Third International Symposium on Selenium in Biology and Medicine . Westport, Conn: AVI Publishing Co; 1986:1122-1135. 35. Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China . J Natl Cancer Inst . 1993;85:1483-1492.Crossref 36. Li JY, Taylor PR, Li B. Nutrition intervention trials in Linxian, China . J Natl Cancer Inst . 1993; 85:1492-1498.Crossref 37. Olson OE, Palmer IS, Cary EE. Modification of the official fluorometric method for selenium in plants . J Assoc Off Anal Chem . 1975;58:117-126. 38. McShane LM, Clark LC, Combs GF Jr, Turnbull BW. Reporting the accuracy of biochemical measurements for epidemiologic and nutrition studies . Am J Clin Nutr . 1991;53:1354-1360. 39. Abu-Libdeh H, Turnbull BW, Clark LC. Analysis of multi-type recurrent events in longitudinal studies . Biometrics . 1990;46:1017-1023.Crossref 40. Luo X, Turnbull BW, Cai H, Clark LC. Regression for censored survival data with lag effects . Commun Stat . 1994;23:3417-3438.Crossref 41. Allaway WH, Kubota J, Losee F, Roth M. Selenium, molybdenum and vanadium in human blood . Arch Environ Health . 1968;16:342-348.Crossref 42. National Cancer Institute, State Cancer Control and Data Program. Cancer Mortality by Pentad 1953-1957 to 1983-1987 . Bethesda, Md: National Institutes of Health; 1992. 43. Nelson MA, Einspahr JG, Alberts DS, et al. Analysis of the p53 gene in human precancerous actinic keratosis lesions and squamous cell cancers . Cancer Lett . 1994;85:23-29.Crossref 44. Gailani MR, Leffell DJ, Ziegler A, Gross EG, Brash DE, Bale AE. Relationship between sunlight exposure and a key genetic alteration in basal cell carcinoma . J Natl Cancer Inst . 1996;88:349-354.Crossref 45. Lanfear J, Fleming J, Wu L, Webster G, Harrison PR. The selenium metabolite selenodiglutathione induces p53 and apoptosis . Carcinogenesis . 1994; 15:1378-1392.Crossref 46. Yang GQ, Yin S, Zhou R. Studies of safe maximal daily dietary Se-intake in a seleniferous area of China . J Trace Elem Electrolytes Health Dis . 1989;3:123-130. 47. Thompson JH, Wilson A, Lu J, et al. Comparison of the effects of an organic and inorganic form of selenium on a mammary carcinoma cell line . Carcinogenesis . 1994;15:183-186.Crossref 48. Pahor M, Gurainik JM, Ferrucci L, et al. Calcium channel blockade and incidence of cancer in aged populations . Lancet . 1996;348:493-497.Crossref 49. The LRC Study Group. The Lipid Research Clinics Coronary Primary Prevention Trial results . JAMA . 1984;251:351-364.Crossref 50. Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia . N Engl J Med . 1987;317:1237-1245.Crossref 51. Comstock GW, Bush TL, Helzlsouer K. Serum retinol, beta-carotene, vitamin E and selenium as related to subsequent cancer of specific sites . Am J Epidemiol . 1992;135:115-121. 52. Pocock SJ, Geller NL, Tsiatis AA. The analysis of multiple endpoints in clinical trials . Biometrics . 1987;43:487-498.Crossref 53. Rothman KJ. No adjustments are needed for multiple comparisons . Epidemiology . 1990;1:43-46.Crossref 54. Tannock IF. False-positive results in clinical trials . J Natl Cancer Inst . 1996;88:206-207.Crossref 55. Cook RJ, Farewell VT. Multiplicity considerations in the design and analysis of clinical trials . J R Stat Soc A . 1996;159:93-110.Crossref 56. Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient, I: introduction and design . Br J Cancer . 1976;34:585-612.Crossref 57. Cox DR. In Discussion: Jennison C, Turnbull BW. Interim analyses . J R Stat Soc B . 1989;51:338. 58. Jennison C, Turnbull BW. Interim analyses . J R Stat Soc B . 1989;51:305-361.

Journal

JAMAAmerican Medical Association

Published: Dec 25, 1996

There are no references for this article.