Lessons learned from randomized clinical trials of micronutrient supplementation for cancer prevention

Annual Review of Nutrition

Volumn 32, Issue , 2012, Pages 369-390

  Mayne, Susan T ^a,b   Ferrucci, Leah M ^a   Cartmel, Brenda ^a,b  

^a YALE UNIVERSITY   (United States)

^b YALE CANCER CENTER   (United States)

Author keywords

Beta carotene; Folate; Selenium; Vitamin D; Vitamin E

Indexed keywords

ALPHA TOCOPHEROL; ANTIOXIDANT; ASCORBIC ACID; BETA CAROTENE; FOLIC ACID; RETINOL; SELENIUM; TRACE ELEMENT; VITAMIN D;

BREAST CANCER; CANCER PREVENTION; CANCER RISK; CARCINOGENESIS; COLORECTAL CANCER; ESOPHAGUS CANCER; HEAD AND NECK CANCER; HUMAN; LUNG CANCER; NONHUMAN; OUTCOME ASSESSMENT; POPULATION RESEARCH; PRECANCER; PRIORITY JOURNAL; PROSTATE CANCER; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SKIN CANCER; STOMACH CANCER; UTERINE CERVIX CANCER; VITAMIN SUPPLEMENTATION;

ANIMALS; ANTIOXIDANTS; DIETARY SUPPLEMENTS; EVIDENCE-BASED MEDICINE; FOLIC ACID; HUMANS; MICRONUTRIENTS; NEOPLASMS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; VITAMIN D;

EID: 84864224849     PISSN: 01999885     EISSN: 15454312     Source Type: Book Series    
DOI: 10.1146/annurev-nutr-071811-150659     Document Type: Review

References (90)

1. Am. Cancer Soc. 2012. Cancer Facts and Figures 2012. Atlanta, GA: Am. Cancer Soc.
2. Bairati I, Meyer F, Jobin E, Gelinas M, Fortin A, et al. 2006. Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. Int. J. Cancer 119:2221-24 (Pubitemid 44423684)
3. Baron JA, Cole BF, Mott L, Haile R, Grau M, et al. 2003. Neoplastic and antineoplastic effects of betacarotene on colorectal adenoma recurrence: results of a randomized trial. J. Natl. Cancer Inst. 95:717-22 (Pubitemid 36665499)
4. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. 2004. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 364:1219-28 (Pubitemid 39311342)
5. Blot WJ, Li JY, Taylor PR, Guo W, Dawsey S, et al. 1993. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J. Natl. Cancer Inst. 85:1483-92 (Pubitemid 23269183)
6. Blount BC, Mack MM, Wehr CM, MacGregor JT, Hiatt RA, et al. 1997. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc. Natl. Acad. Sci. USA 94:3290-95
7. Butterworth CE Jr, Hatch KD, Soong SJ, Cole P, Tamura T, et al. 1992. Oral folic acid supplementation for cervical dysplasia: a clinical intervention trial. Am. J. Obstet. Gynecol. 166:803-9
8. Byers T. 2010. Anticancer vitamins du jour-the ABCED's so far. Am. J. Epidemiol. 172:1-3
9. Byers T, Perry G. 1992. Dietary carotenes, vitamin C, and vitamin E as protective antioxidants in human cancers. Annu. Rev. Nutr. 12:139-59
10. Childers JM, Chu J, Voigt LF, Feigl P, Tamimi HK, et al. 1995. Chemoprevention of cervical cancer with folic acid: a phase III Southwest Oncology Group Intergroup study. Cancer Epidemiol. Biomarkers Prev. 4:155-59
11. Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, Wactawski-Wende J, et al. 2008. Calcium plus vitamin D supplementation and the risk of breast cancer. J. Natl. Cancer Inst. 100:1581-91
12. Chung M, Balk EM, Brendel M, Ip S, Lau J, et al. 2009. Vitamin D and Calcium: A Systematic Review of Health Outcomes. Evidence Report No. 183 (Prepared by the Tufts Evidence-Based Practice Center). Rockville, MD: Agency Healthc. Res. Qual.
13. Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, et al. 1996. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA 276:1957-63 (Pubitemid 26427723)
14. Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, et al. 2007. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 297:2351-59 (Pubitemid 46883748)
15. Correa P, Fontham ET, Bravo JC, Bravo LE, Ruiz B, et al. 2000. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. J. Natl. Cancer Inst. 92:1881-88 (Pubitemid 32036918)
16. de Vet HC, Knipschild PG, Willebrand D, Schouten HJ, Sturmans F. 1991. The effect of beta-carotene on the regression and progression of cervical dysplasia: a clinical experiment. J. Clin. Epidemiol. 44:273-83
17. Duffield-Lillico AJ, Reid ME, Turnbull BW, Combs GF Jr, Slate EH, et al. 2002. 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. Cancer Epidemiol. Biomarkers Prev. 11:630-39 (Pubitemid 34760821)
18. Duffield-Lillico AJ, Slate EH, Reid ME, Turnbull BW, Wilkins PA, et al. 2003. Nutritional Prevention of Cancer Study Group. Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J. Natl. Cancer Inst. 95:1477-81 (Pubitemid 37279333)
19. Duthie SJ, Narayanan S, Blum S, Pirie L, Brand GM. 2000. Folate deficiency in vitro induces uracil misincorporation and DNA hypomethylation and inhibits DNA excision repair in immortalized normal human colon epithelial cells. Nutr. Cancer 37:245-51
20. Ebbing M, Bonaa KH, Nygard O, Arnesen E, Ueland PM, et al. 2009. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 302:2119-26
21. Etminan M, Takkouche B, Caamaño-Isorna F. 2004. The role of tomato products and lycopene in the prevention of prostate cancer: a meta-analysis of observational studies. Cancer Epidemiol. Biomarkers Prev. 13:340-45 (Pubitemid 38737456)
22. Eussen SJ, Vollset SE, Igland J, Meyer K, Fredriksen A, et al. 2010. Plasma folate, related genetic variants, and colorectal cancer risk in EPIC. Cancer Epidemiol. Biomarkers Prev. 19:1328-40
23. Fairfield K, Stampfer M. 2007. Vitamin and mineral supplements for cancer prevention: issues and evidence. Am. J. Clin. Nutr. 85:289-92S
24. Fleshner NE, Kapusta L, Donnelly B, Tanguay S, Chin J, et al 2011. Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium. J. Clin. Oncol. 29:2386-90
25. Fleshner NE, Klotz LH. 1998. Diet, androgens, oxidative stress and prostate cancer susceptibility. Cancer Metastasis Rev. 17:325-30
26. Garland CF, Gorham ED, Mohr SB, Garland FC. 2009. Vitamin D for cancer prevention: global perspective. Ann. Epidemiol. 19:468-83
27. Gaziano JM, Glynn RJ, Christen WG, Kurth T, Belanger C, et al. 2009. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA 301:52-62
28. Giovannucci E. 1999. Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J. Natl. Cancer Inst. 91:317-31 (Pubitemid 29102331)
29. Giovannucci E. 2002. Epidemiologic studies of folate and colorectal neoplasia: a review. J. Nutr. 132:2350- 55S
30. Giuliano AR, Gapstur S. 1998. Can cervical dysplasia and cancer be prevented with nutrients? Nutr. Rev. 56:9-16 (Pubitemid 28068653)
31. Green A, WilliamsG, Neale R, Hart V, Leslie D, et al. 1999. Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. Lancet 354:723-29 (Pubitemid 29405786)
32. Greenberg ER, Baron JA, Stukel TA, Stevens MM, Mandel JS, et al. 1990. A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin. The Skin Cancer Prevention Study Group. N. Engl. J. Med. 323:789-95 (Pubitemid 20303876)
33. Greenberg ER, Baron JA, TostesonTD, FreemanDH Jr, Beck GJ, et al. 1994.Aclinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. N. Engl. J. Med. 331:141-47 (Pubitemid 24209563)
34. Handelman GJ, Epstein WL, Peerson J, Spiegelman D, Machlin LJ, Dratz EA. 1994. Human adipose alpha-tocopherol and gamma-tocopherol kinetics during and after 1 y of alpha-tocopherol supplementation. Am. J. Clin. Nutr. 59:1025-32
35. Heart Protect. Study Collab. Group. 2002. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20, 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360:23-33
36. Heinonen OP, Albanes D, Virtamo J, Taylor PR, Huttunen JK, et al. 1998. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J. Natl. Cancer Inst. 90:440-46 (Pubitemid 28160635)
37. Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, et al. 1996. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N. Engl. J. Med. 334:1145-49 (Pubitemid 26137972)
38. Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, et al. 2004. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch. Intern. Med. 164:2335-42 (Pubitemid 39532244)
39. Intl. Agency Res. Cancer, Work. Group Vitamin D. 2008. Vitamin D and Cancer. Geneva:World Health Org. Press
40. Inst.Med. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: Natl. Acad. Press
41. Jacobs EJ, Connell CJ, Patel AV, Chao A, Rodriguez C, et al. 2001. Multivitamin use and colon cancer mortality in the Cancer Prevention Study II cohort (United States). Cancer Causes Control 12:927-34 (Pubitemid 34048874)
42. Jaszewski R, Misra S, Tobi M, Ullah N, Naumoff JA, et al. 2008. Folic acid supplementation inhibits recurrence of colorectal adenomas: a randomized chemoprevention trial. World J. Gastroenterol. 14:4492-98
43. Keefe KA, Schell MJ, Brewer C, McHale M, Brewster W, et al. 2001. A randomized, double blind, Phase III trial using oral beta-carotene supplementation for women with high-grade cervical intraepithelial neoplasia. Cancer Epidemiol. Biomarkers Prev. 10:1029-35 (Pubitemid 32959149)
44. Kikendall JW, Mobarhan S, Nelson R, Burgess M, Bowen PE. 1991. Oral beta carotene does not reduce the recurrence of colorectal adenomas. Am. J. Gastroenterol. 36:1356 (Abstr.)
45. Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, et al. 2011. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 306:1549-56
46. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. 2007. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am. J. Clin. Nutr. 85:1586-91 (Pubitemid 46890428)
47. Larsson SC, Orsini N, Wolk A. 2010. Vitamin B6 and risk of colorectal cancer: ameta-analysis of prospective studies. JAMA 303:1077-83
48. Ledesma MC, Jung-Hynes B, Schmit TL, Kumar R, Mukhtar H, Ahmad N. 2010. Selenium and vitamin E for prostate cancer: post-SELECT (Selenium and Vitamin E Cancer Prevention Trial) status. Mol. Med. 17:134-43
49. Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH. 1999. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: theWomen's Health Study. J. Natl. Cancer Inst. 91:2102-6 (Pubitemid 30019571)
50. Lee JJ, Wu X, Hildebrandt MA, Yang H, Khuri FR, et al. 2011. Global assessment of genetic variation influencing response to retinoid chemoprevention in head and neck cancer patients. Cancer Prev. Res. (Phila.) 4:185-93
51. Levine N, Moon TE, Cartmel B, Bangert JL, Rodney S, et al. 1997. Trial of retinol and isotretinoin in skin cancer prevention: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol. Biomarkers Prev. 6:957-61 (Pubitemid 27481645)
52. Li JY, Taylor PR, Li B, Dawsey S, Wang GQ, et al. 1993. Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia. J. Natl. Cancer Inst. 85:1492-98 (Pubitemid 23269184)
53. Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, et al. 2009. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 301:39-51
54. Lippman SM, Lee JJ, Karp DD, Vokes EE, Benner SE, et al. 2001. Randomized phase III intergroup trial of isotretinoin to prevent second primary tumors in stage I non-small-cell lung cancer. J. Natl. Cancer Inst. 93:605-18
55. Liu C, Wang XD, Bronson RT, Smith DE, KrinskyNI, Russell RM. 2000. Effects of physiological versus pharmacological beta-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets. Carcinogenesis 21:2245-53 (Pubitemid 32049231)
56. Lodi G, Sardella A, Bez C, Demarosi F, Carrassi A. 2006. Interventions for treating oral leukoplakia. Cochrane Database Syst. Rev. 4:CD001829
57. Logan RF, Grainge MJ, Shepherd VC, Armitage NC, Muir KR. 2008. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology 134:29-38 (Pubitemid 350309319)
58. Mackerras D, Irwig L, Simpson JM, Weisberg E, CardonaM, et al. 1999. Randomized double-blind trial of beta-carotene and vitamin C in women with minor cervical abnormalities. Br. J. Cancer 79:1448-53 (Pubitemid 29116803)
59. MacLennan R, Macrae F, Bain C, Battistutta D, Chapuis P, et al. 1995. Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas. J. Natl. Cancer Inst. 87:1760-66
60. Manson JE, Bassuk SS, Lee IM, Cook NR, Albert MA, et al. 2012. The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp. Clin. Trials 33:159-71
61. Marshall JR, Tangen CM, Sakr WA, Wood DP Jr, Berry DL, et al. 2011. Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia: SWOG S9917. Cancer Prev. Res. (Phila.) 4:1761-69
62. Mayne S. 1998. Beta-carotene, carotenoids, and cancer prevention. Principles Practice Oncol. Updates 12:1-15
63. Mayne S, Cartmel B, Morse D. 2003. Chemoprevention of oral premalignant lesions. In Head and Neck Cancer: Emerging Perspectives, ed. JF Ensley, JS Gutkind, JR Jacobs, SMLippman, pp. 261-69. New York: Academic
64. Mayne ST, Cartmel B, BaumM, Shor-PosnerG, Fallon BG, et al. 2001. Randomized trial of supplemental beta-carotene to prevent second head and neck cancer. Cancer Res. 61:1457-63 (Pubitemid 34292573)
65. Mayne ST, Graham S, Zheng TZ. 1991. Dietary retinol: prevention or promotion of carcinogenesis in humans? Cancer Causes Control 2:443-50
66. Mayne ST, Gruber SB. 2009. Emerging molecular technologies for identifying the risk of second cancers. Cancer Prev. Res. (Phila.) 2:605-7
67. Mayne ST, Vogt TM 2000. Antioxidant nutrients in cancer prevention. Principles Practice Oncol. Updates 14:1-12
68. McLarty JW, Holiday DB, Girard WM, Yanagihara RH, Kummet TD, Greenberg SD. 1995. Betacarotene, vitamin A and lung cancer chemoprevention: results of an intermediate endpoint study. Am. J. Clin. Nutr. 62:1431-38S
69. Moon TE, Levine N, Cartmel B, Bangert JL, Rodney S, et al. 1997. Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol. Biomarkers Prev. 6:949-56 (Pubitemid 27481644)
70. MuñozN, Wahrendorf J, Bang LJ, Crespi M, Thurnham DI, et al. 1985. No effect of riboflavine, retinol, and zinc on prevalence of precancerous lesions of oesophagus. Randomised double-blind intervention study in high-risk population of China. Lancet 2:111-14 (Pubitemid 15046291)
71. Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, et al. 1996. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N. Engl. J. Med. 334:1150-55 (Pubitemid 26137973)
72. Paspatis GA, Karamanolis DG. 1994. Folate supplementation and adenomatous colonic polyps. Dis. Colon Rectum 37:1340-41
73. Qiao YL, Dawsey SM, Kamangar F, Fan JH, Abnet CC, et al. 2009. Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial. J. Natl. Cancer Inst. 101:507-18
74. Romney SL, Ho GY, Palan PR, Basu J, Kadish AS, et al. 1997. Effects of beta-carotene and other factors on outcome of cervical dysplasia and human papillomavirus infection. Gynecol. Oncol. 65:483-92 (Pubitemid 27255993)
75. SanjoaquinMA, Allen N, Couto E, Roddam AW, Key TJ. 2005. Folate intake and colorectal cancer risk: a meta-analytical approach. Int. J. Cancer 113:825-28 (Pubitemid 40101266)
76. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. 2007. Human papillomavirus and cervical cancer. Lancet 370:890-907 (Pubitemid 47371147)
77. The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group. 1994. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J. Med. 330:1029-35
78. Toma S, Bonelli L, Sartoris A, Mira E, Antonelli A, et al. 2003. Beta-carotene supplementation in patients radically treated for stage I-II head and neck cancer: results of a randomized trial. Oncol. Rep. 10:1895-901
79. Toner CD, Davis CD, Milner JA. 2010. The vitaminDand cancer conundrum: aiming at a moving target. J. Am. Diet. Assoc. 110:1492-500
80. Trivedi DP, Doll R, Khaw KT. 2003. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 326:469
81. Trottier G, Bostrom PJ, Lawrentschuk N, Fleshner NE. 2010. Nutraceuticals and prostate cancer prevention: a current review. Nat. Rev. Urol. 7:21-30
82. van Zandwijk N, Dalesio O, Pastorino U, de Vries N, van Tinteren H. 2000. EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the European Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups. J. Natl. Cancer Inst. 92:977-86 (Pubitemid 30469963)
83. VisserM, Deeg DJ, Puts MT, Seidell JC, Lips P. 2006. Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission. Am. J. Clin. Nutr. 84:616-22; quiz 671-72 (Pubitemid 44713413)
84. Wactawski-Wende J, Kotchen JM, AndersonGL, Assaf AR, BrunnerRL, et al. 2006. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N. Engl. J. Med. 354:684-96 (Pubitemid 43247139)
85. WangXD, Liu C, BronsonRT, SmithDE, KrinskyNI, RussellRM.1999. Retinoid signaling and activator protein-1 expression in ferrets given beta-carotene supplements and exposed to tobacco smoke. J. Natl. Cancer Inst. 91:60-66 (Pubitemid 29042444)
86. White E, Shannon JS, Patterson RE. 1997. Relationship between vitamin and calcium supplement use and colon cancer. Cancer Epidemiol. Biomarkers Prev. 6:769-74 (Pubitemid 27435473)
87. World Cancer Res. Fund/Am. Inst. Cancer Res. 2007. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington, DC: Am. Inst. Cancer Res.
88. Wu K, Platz EA, Willett WC, Fuchs CS, Selhub J, et al. 2009. A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma. Am. J. Clin. Nutr. 90:1623-31
89. You WC, Brown LM, Zhang L, Li JY, Jin ML, et al. 2006. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J. Natl. Cancer Inst. 98:974-83 (Pubitemid 44288162)
90. Zaridze D, Evstifeeva T, Boyle P. 1993. Chemoprevention of oral leukoplakia and chronic esophagitis in an area of high incidence of oral and esophageal cancer. Ann. Epidemiol. 3:225-34 (Pubitemid 23169425)