Review Article | Published:

Are vitamin and mineral deficiencies a major cancer risk?

Nature Reviews Cancer volume 2, pages 694704 (2002) | Download Citation



Diet is estimated to contribute to about one-third of preventable cancers — about the same amount as smoking. Inadequate intake of essential vitamins and minerals might explain the epidemiological findings that people who eat only small amounts of fruits and vegetables have an increased risk of developing cancer. Recent experimental evidence indicates that vitamin and mineral deficiencies can lead to DNA damage. Optimizing vitamin and mineral intake by encouraging dietary change, multivitamin and mineral supplements, and fortifying foods might therefore prevent cancer and other chronic diseases.

Key points

  • Acute deficiencies of vitamins and minerals are rare in developed countries, but suboptimal nutrient intake — less than the recommended daily allowance (RDA) — is a widespread problem. Research indicates that considerable metabolic damage can still occur when nutrient intake levels fall below the RDA — even though they might not cause acute disease.

  • Evidence indicates that deficiencies of iron and zinc, and the vitamins folate, B12, B6 and C, can cause DNA damage and lead to cancer.

  • New animal bioassays of nutritional deficiencies are needed, particularly for studying cancer.

  • Reduced folate intake has been associated with cancer. Folate, B6 and B12 deficiencies cause the incorporation of deoxyuracil into DNA, leading to DNA breakage, and could promote tumorigenesis.

  • The relationship of vitamin and mineral deficiencies and cancer is extremely complex. An integrated analysis of the findings from epidemiological, animal-model, metabolic and intervention studies, as well as from genetic polymorphism research, is required.

  • Approaches to eliminating micronutrient deficiencies include improving diet, fortifying foods and providing multivitamin and mineral supplements. Prevention strategies such as these could have a significant impact on cancer and public health, with minimal risk being involved.

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  1. 1.

    & The Causes of Cancer (University Press, Oxford, 1981). (Reference deleted in proof.)This classical paper discusses the risk of cancer and the link to lifestyle factors.

  2. 2.

    et al. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc. Natl Acad. Sci. USA 99, 1870–1875 (2002).

  3. 3.

    et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha-lipoic acid. Proc. Natl Acad. Sci. USA 99, 2356–2361 (2002).

  4. 4.

    , & Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L-carnitine and/or R-alpha-lipoic acid. Proc. Natl Acad. Sci. USA 99, 1876–1881 (2002).

  5. 5.

    , & High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased Km): relevance to genetic disease and polymorphisms. Am. J. Clin. Nutr. 75, 616–658 (2002).

  6. 6.

    DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat. Res. 475, 7–20 (2001).Discusses how various micronutrient deficiencies can lead to DNA damage and cancer.

  7. 7.

    et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage. Proc. Natl Acad. Sci. USA 94, 3290–3295 (1997).The results of this study provide evidence that folate status can be a key determinant of DNA strand breaks.

  8. 8.

    Dietary factors affecting spontaneous chromosomal damage in man. Prog. Clin. Biol. Res. 347, 139–153 (1990).

  9. 9.

    et al. Ascorbic acid protects against endogenous oxidative damage in human sperm. Proc. Natl Acad. Sci. USA 88, 11003–11006 (1991).

  10. 10.

    Eat, Drink, and Be Healthy (Simon & Schuster Source, New York, 2001).

  11. 11.

    Diet and breast cancer. J. Intern. Med. 249, 395–411 (2001).

  12. 12.

    Diet and cancer: one view at the start of the millennium. Cancer Epidemiol. Biomarkers Prev. 10, 3–8 (2001).Describes the process by which diet and cancer relationships have been investigated epidemiologically in the past few decades, using fat and breast cancer as an example. Dietary methodology issues, as well as other epidemiological issues, are discussed.

  13. 13.

    & Can diet affect prostate cancer? Br. J. Urol. 89, 250–254 (2002).

  14. 14.

    in Present Knowledge in Nutrition (eds Bowman, B. A. & Russell, R. M.) 573–589 (ILSI International Life Sciences Institute, Washington DC, 2001).

  15. 15.

    Meat consumption and cancer of the large bowel. Eur. J. Clin. Nutr. 56 (Suppl. 1), S19–S24 (2002).

  16. 16.

    World Cancer Research Fund. American Institute for Cancer Research, Food Nutrition and the Prevention of Cancer: a global perspective (World Cancer Research Fund, Washington DC, 1997).This is the most comprehensive review so far on the many aspects of the relationship of diet to cancer.

  17. 17.

    & Vitamin D and cancer. J. Nutr. Biochem. 13, 252–264 (2002).

  18. 18.

    et al. Plasma 1,25 dihydroxy- and 25-hydroxyvitamin D and adenomatous polyps of the distal colorectum. Cancer Epidemiol. Biomarkers Prev. 9, 1059–1065 (2000).

  19. 19.

    , & Fruit, vegetables and cancer prevention: a review of the epidemiologic evidence. Nutr. Cancer 18, 1–29 (1992).This review found a statistically significant protective effect of fruit and vegetable consumption in 128 out of 156 studies in which results were expressed in terms of relative risk.

  20. 20.

    & Vegetables, fruit, and cancer. I. Epidemiology. Cancer Causes Control 2, 325–357 (1991).This was the first comprehensive scientific review that concluded that consumption of higher levels of vegetables and fruit is associated consistently, although not universally, with a reduced risk of cancer at most sites.

  21. 21.

    & Vegetables, fruit, and cancer prevention: a review. J. Am. Diet Assoc. 96, 1027–1039 (1996).

  22. 22.

    et al. Fruit, vegetables, dietary fiber, and risk of colorectal cancer. J. Natl Cancer Inst. 93, 525–533 (2001).

  23. 23.

    et al. Fruits, vegetables and adenomatous polyps. Am. J. Epidemiol. 155, 1104–1113 (2002).

  24. 24.

    et al. Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies. JAMA 285, 769–776 (2001).

  25. 25.

    et al. Vegetable and fruit consumption and risks of colon and rectal cancer in prospective cohort sutdy: The Netherlands Cohort Study on Diet and Cancer. Am. J. Epidemiol. 152, 1081–1092 (2000).

  26. 26.

    et al. Whole grain food intake and cancer risk. Int. J. Cancer 77, 24–28 (1998).

  27. 27.

    , , & Whole-grain intake and cancer: an expanded review and meta-analysis. Nutr. Cancer 30, 85–96 (1998).

  28. 28.

    , & in Primary and Secondary Preventive Nutrition (eds Bendich, A. & Deckelbaum, R. J.) 21–43 (Humana Press, Totowa, New Jersey, 2001).

  29. 29.

    & Vegetables, fruit, and cancer. II. Mechanisms. Cancer Causes Control 2, 427–442 (1991).

  30. 30.

    & Cruciferous vegetables and cancer prevention. Nutr. Cancer 41, 17–28 (2001).

  31. 31.

    Strategies for cancer prevention: the role of diet. Br. J. Nutr. 87, S265–S272 (2002).

  32. 32.

    Cancer prevention and diet: help from single nucleotide polymorphisms. Proc. Natl Acad. Sci. USA 96, 12216–12218 (1999).

  33. 33.

    , & DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis. Environ. Health Perspect. 101 (Suppl. 5), 35–44 (1993).

  34. 34.

    Carcinogenesis mechanisms: the debate continues. Science 252, 902 (1991).

  35. 35.

    Mutation and cancer: the antecedents to our studies of adaptive mutation. Genetics 148, 1433–1440 (1998).

  36. 36.

    & Hormonal carcinogenesis. Carcinogenesis 21, 427–433 (2000).

  37. 37.

    & Selection, the mutation rate and cancer: ensuring that the tail does not wag the dog. Nature Med. 5, 11–12 (1999).

  38. 38.

    , , , & A critical evaluation of the application of biomarkers in epidemiological studies on diet and health. Br. J. Nutr. 86 (Suppl 1), S37–S53 (2001).

  39. 39.

    & Paracelsus to parascience: the environmental cancer distraction. Mutat. Res. 447, 3–13 (2000).

  40. 40.

    , & What do animal cancer tests tell us about human cancer risk? Overview of analyses of the carcinogenic potency database. Drug Metab. Rev. 30, 359–404 (1998).This paper describes the Carcinogenic Potency Database (CPDB), which analyses and standardizes the literature of chronic carcinogenicity tests in laboratory animals. It discusses the usefulness of CPDB in addressing questions about the use of animal bioassays in the evaluation of potential cancer risks to humans.

  41. 41.

    et al. Alcohol, methyl-deficient diets and risk of colon cancer in men. J. Natl Cancer Inst. 87, 265–273 (1995).

  42. 42.

    et al. Multivitamin use, folate, and colon cancer in women in the nurses' health study. Ann. Intern. Med. 129, 517–524 (1998).

  43. 43.

    , , & Dietary folate consumption and breast cancer risk. J. Natl Cancer Inst. 92, 266–269 (2000).

  44. 44.

    et al. A prospective study of folate intake and the risk of breast cancer. JAMA 281, 632–637 (1999).

  45. 45.

    et al. Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am. J. Epidemiol. 153, 680–687 (2001).

  46. 46.

    et al. Pancreatic cancer risk and nutrition-related methyl-group availability indicators in male smokers. J. Natl Cancer Inst. 91, 535–541 (1999).

  47. 47.

    et al. Nutrient intake and risk of subtypes of esophageal and gastric cancer. Cancer Epidemiol. Biomarkers Prev. 10, 1055–1062 (2001).

  48. 48.

    , , & Methylenetetrahydrofolate reductase C677T polymorphism does not alter folic acid deficiency-induced uracil incorporation into primary human lymphocyte DNA in vitro. Carcinogenesis 22, 1019–1025 (2001).

  49. 49.

    , & Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. Carcinogenesis 19, 1163–1171 (1998).

  50. 50.

    Micronutrients and genomic stability: a new paradigm for recommended dietary allowances (RDAs). Food Chem. Toxicol. 40, 1113–1117 (2002).

  51. 51.

    et al. Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). Cancer Res. 58, 4117–4121 (1998).

  52. 52.

    et al. A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res. 56, 4862–4864 (1996).

  53. 53.

    et al. B-vitamin intake, metabolic genes, and colorectal cancer risk (United States). Cancer Causes Control 13, 239–248 (2002).

  54. 54.

    et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res. 57, 1098–1102 (1997).

  55. 55.

    , , , & Methylenetetrahydrofolate reductase, diet, and risk of colon cancer. Cancer Epidemiol. Biomarkers Prev. 8, 513–518 (1999).

  56. 56.

    et al. The methylenetetrahydrofolate reductase 677C→T polymorphism and distal colorectal adenoma risk. Cancer Epidemiol. Biomarkers Prev. 9, 657–663 (2000).

  57. 57.

    et al. Colorectal adenomas and the C677T MTHFR polymorphism: evidence for gene-environment interaction? Cancer Epidemiol. Biomarkers Prev. 8, 659–668 (1999).

  58. 58.

    et al. Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. Proc. Natl Acad. Sci. USA 96, 12810–12815 (1999).Shows the power of single-nucleotide polymorphisms in epidemiological studies to clarify mechanisms and risk factors in the area of diet and disease prevention.

  59. 59.

    et al. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc. Natl Acad. Sci. USA 98, 4004–4009 (2001).

  60. 60.

    et al. Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia. Cancer Epidemiol. Biomarkers Prev. 10, 1275–1280 (2001).

  61. 61.

    et al. Low seminal plasma folate concentrations are associated with low sperm density and count in male smokers and nonsmokers. Fertil. Steril. 75, 252–259 (2001).Folate deficiency in men causes uracil incorporation in sperm DNA and decreased sperm count and quality.

  62. 62.

    , & in Preventive Nutrition: The Comprehensive Guide for Health Professionals (eds Bendich, A. & Deckelbaum, R. J.) 373–386 (Humana Press, Inc., Totowa, New Jersey, 2001).

  63. 63.

    , & Folate, vitamin B12, homocysteine status and chromosome damage rate in lymphocytes of older men. Carcinogenesis 18, 1329–1336 (1997).

  64. 64.

    Micronucleus frequency in human lymphocytes is related to plasma vitamin B12 and homocysteine. Mutat. Res. 428, 299–304 (1999).

  65. 65.

    , , & Elevations of serum cystathionine and total homocysteine in pyridoxine-, folate-, and cobalamin-deficient rats. J. Nutr. Biochem. 8, 279–289 (1997).

  66. 66.

    et al. The risk of cervical cancer in relation to serum concentrations of folate, vitamin B12, and homocysteine. Cancer Epidemiol. Biomarkers Prev. 9, 761–764 (2000).

  67. 67.

    et al. A prospective study on folate, B12, and pyridoxal 5′-phosphate (B6) and breast cancer. Cancer Epidemiol. Biomarkers Prev. 8, 209–217 (1999).

  68. 68.

    , , , & A case–control study of diet and prostate cancer. Br. J. Cancer 76, 678–687 (1997).

  69. 69.

    et al. Association of B-vitamins pyrodoxal 5′-phosphate (B(6)), B(12) and folate with lung cancer risk in older men. Am. J. Epidemiol. 153, 688–694 (2001).

  70. 70.

    et al. Elevated serum homocysteine levels and increased risk of invasive cervical cancer in US women. Cancer Causes Control 12, 317–324 (2001).

  71. 71.

    in Nutrition in Health and Disease (eds Shils, M., Olson, J. A. & Shike, M.) 467–484 (Williams & Wilkins, Baltimore, 1999).

  72. 72.

    , & Oxidants, antioxidants, and the degenerative diseases of aging. Proc. Natl Acad. Sci. USA 90, 7915–7922 (1993).

  73. 73.

    & Nutrition and stomach cancer. Cancer Causes Control 7, 41–55 (1996).

  74. 74.

    , & Effect of physiological concentrations of vitamin C on gastric cancer cell and Helicobacter pylori. Gut 50, 165–169 (2002).

  75. 75.

    & Oxidative DNA damage in human white blood cells in dietary antioxidant intervention studies. Am. J. Clin. Nutr. 76, 303–310 (2002).

  76. 76.

    et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc. Natl Acad. Sci. USA 93, 3704–3709 (1996).

  77. 77.

    , , & Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes. Cancer Res. 56, 1291–1295 (1996).

  78. 78.

    et al. Citrus fruit supplementation reduces lipoprotein oxidation in young men ingesting a diet high in saturated fat: presumptive evidence for an interaction between vitamins C and E in vivo. Am. J. Clin. Nutr. 67, 240–245 (1998).

  79. 79.

    & Can antioxidant vitamins materially reduce oxidative damage in humans? Free Radic. Biol. Med. 26, 1034–1053 (1999).This review examines the scientific evidence that supplementation of humans with vitamin C, vitamin E or β-carotene lowers in vivo oxidative damage to lipids, proteins or DNA based on the measurement of oxidative biomarkers.

  80. 80.

    in Vitamin C: The State of the Art in Disease Prevention Sixty Years after the Nobel Prize (eds Paoletti, R., Sies, H., Bug, J., Grossi, E. & Poli, A.) 51–58 (Springer–Verlag, Milano, 1998).

  81. 81.

    & Epidemiologic evidence for vitamin C and vitamin E in cancer prevention. Am. J. Clin. Nutr. 62(6 Suppl), 1385S–1392S (1995).

  82. 82.

    & The role of ascorbic acid in oral cancer and carcinogenesis. Oral Dis. 4, 120–129 (1998).

  83. 83.

    et al. Vitamin C, vitamin E, and multivitamin supplement use and stomach cancer mortality in the Cancer Prevention Study II cohort. Cancer Epidemiol. Biomarkers Prev. 11, 35–41 (2002).

  84. 84.

    et al. Vitamin C and Vitamin E supplement use and colorectal cancer mortality in a large American Cancer Society cohort. Cancer Epidemiol. Biomarkers Prev. 10, 17–23 (2001).

  85. 85.

    et al. Antioxidant supplementation decreases lipid peroxidation biomarker F(2)-isoprostanes in plasma of smokers. Cancer Epidemiol. Biomarkers Prev. 11, 7–13 (2002).

  86. 86.

    , , , & Serum carotenoids and oxidative DNA damage in human lymphocytes. Carcinogenesis 19, 2159–2162 (1998).

  87. 87.

    & Ex vivo assessment of lymphocyte antioxidant status using the Comet Assay. Free Rad. Res. 27, 533–537 (1997).This study reports results that the three main antioxidants have a demonstrable, short-term protective effect against oxidative DNA damage, which is widely regarded as an important element in the aetiology of cancer.

  88. 88.

    , , & A simpler, more robust method for the analysis of 8-oxoguanine in DNA. Free Radic. Biol. Med. 29, 357–367 (2000).

  89. 89.

    et al. DNA oxidation matters: the HPLC-EC assay of 8-oxo-deoxyguanosine and 8-oxo-guanine. Proc. Natl Acad. Sci. USA 95, 288–293 (1998).

  90. 90.

    & Folate deficiency increases genetic damage caused by alkylating agents and gamma-irradiation in Chinese hamster ovary cells. Cancer Res. 53, 5401–5408 (1993).

  91. 91.

    Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium and Carotenoids (National Academy Press, Washington DC, 2001).

  92. 92.

    , , , & Smoking and low antioxidant levels increase oxidative damage to sperm DNA. Mutat. Res. 351, 199–203 (1996).

  93. 93.

    et al. Ascorbate is depleted by smoking and repleted by moderate supplementation: a study in male smokers and nonsmokers with matched dietary antioxidant intakes. Am. J. Clin. Nutr. 71, 530–536 (2000).

  94. 94.

    et al. Childhood cancer and parental use of tobacco: deaths from 1971 to 1976. Br. J. Cancer 76, 1525–1531 (1997).

  95. 95.

    , , , & Childhood cancer and parental use of alcohol and tobacco. Ann. Epidemiol. 5, 354–359 (1995).

  96. 96.

    , , , & Childhood cancer and parental use of tobacco deaths from 1953 to 1955. Br. J. Cancer 75, 134–138 (1997).

  97. 97.

    et al. Paternal cigarette smoking and the risk of childhood cancer among offspring of nonsmoking mothers. J. Natl Cancer Inst. 89, 238–244 (1997).Lymphoma, acute lymphocytic leukaemia and brain cancer are each increased three- to fourfold in the offspring of men who smoke.

  98. 98.

    Iron-induced carcinogenesis: the role of redox regulation. Free Radic. Biol. Med. 20, 553–566 (1996).

  99. 99.

    in Present Knowledge in Nutrition (eds Bowman, B. A. & Russell, R. M.) 311–328 (ILSI Press, Washington DC, 2001).

  100. 100.

    Iron and colorectal cancer risk: human studies. Nutr. Rev. 59, 140–148 (2001).

  101. 101.

    et al. Vitamin E inhibits apoptosis, DNA modification, and cancer incidence induced by iron-mediated peroxidation in Wistar rat kidney. Cancer Res. 57, 2410–2414 (1997).

  102. 102.

    et al. Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats. Proc. Natl Acad. Sci. USA 99, 2264–2269 (2002).

  103. 103.

    , & The role of heme and iron-sulfur clusters in mitochondrial biogenesis, maintenance, and decay with age. Arch. Biochem. Biophys. 397, 345–353 (2002).

  104. 104.

    , & Zinc homeostasis in humans. J. Nutr. 130, 1360S–1366S (2000).Provides background information on zinc metabolism and describes how adjustments in zinc homeostasis occur in animals and humans.

  105. 105.

    Assessment of marginal zinc status in humans. J. Nutr. 130, 1350S–1354S (2000).

  106. 106.

    , , , & Zinc: health effects and research priorities for the 1990s. Environ. Health Perspect. 102 (Suppl 2), 5–46 (1994).

  107. 107.

    & in Nutrition in Health and Disease (eds Shils, M., Olson, J. A. & Shike, M.) 223–239 (Williams & Wilkins, Baltimore, 1999).

  108. 108.

    Metal replacement in DNA-binding zinc finger proteins and its relevance to mutagenicity and carcinogenicity through free radical generation. Nutrition 11, 646–649 (1995).

  109. 109.

    , & The DNA-binding domain of p53 contains the four conserved regions and the major mutation hot spots. Genes Dev. 7, 2556–2564 (1993).

  110. 110.

    & Zinc deficiency induces APE/Ref–1 expression and induces DNA damage in C6 glioma cells. Free Rad. Biol. Med. 31, 518 (2001).

  111. 111.

    , , & Zinc deficiency increases the frequency of single-strand DNA breaks in rat liver. Nutr. Res. 12, 721–736 (1992).

  112. 112.

    et al. Maternal dietary zinc influences DNA strand break and 8-hydroxy-2′-deoxyguanosine levels in infant rhesus monkey liver. Proc. Soc. Exp. Biol. Med. 203, 461–466 (1993).

  113. 113.

    , , & Oxidant defense systems in testes from zinc-deficient rats (44040). Proc. Soc. Exp. Biol. Med. 213, 85–91 (1996).

  114. 114.

    , , , & Fpg protein of Escherichia coli is a zinc finger protein whose cysteine residues have a structural and/or functional role. J. Biol. Chem. 268, 9063–9070 (1993).

  115. 115.

    , & Esophageal carcinogenesis in the rat: zinc deficiency, DNA methylation and alkyltransferase activity. Pathobiology 65, 253–263 (1997).

  116. 116.

    , , & Induction of esophageal tumors in zinc-deficient rats by single low doses of N-nitrosomethylbenzylamine (NMBA): analysis of cell proliferation, and mutations in H-ras and p53 genes. Carcinogenesis 18, 1477–1484 (1997).

  117. 117.

    , , & Cell proliferation and esophageal carcinogenesis in the zinc-deficient rat. Carcinogenesis 17, 1841–1848 (1996).

  118. 118.

    , & Esophageal cancer prevention in zinc-deficient rats: rapid induction of apoptosis by replenishing zinc. J. Natl Cancer Inst. 93, 1525–1533 (2001).

  119. 119.

    , , & Protective action of zinc against cobalt-induced testicular damage in the mouse. Reprod. Toxicol. 7, 49–54 (1993).

  120. 120.

    , & Concentrations of cadmium, lead, selenium and zinc in human blood and seminal plasma. Biol. Trace Element Res. 40, 49–57 (1994).

  121. 121.

    et al. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled study. Fertil. Steril. 77, 491–498 (2002).

  122. 122.

    in Antioxidant Food Supplements in Human Health (eds Packer, L., Hiramatsu, M. & Yoshikawa, T.) 45–54 (Academic Press, San Diego, 1999).

  123. 123.

    et al. Use of multivitamin/mineral prenatal supplements: influence on the outcome of pregnancy. Am. J. Epidemiol. 146, 134–141 (1997).Examines the association of prenatal multivitamin and mineral supplements during the first two trimesters of pregnancy and birth outcomes. Risk for preterm delivery and low birth weight was reduced with supplement use.

  124. 124.

    & What vitamins should I be taking, Doctor? N. Engl. J. Med. 345, 1819–1824 (2001).

  125. 125.

    et al. Alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J. Natl Cancer Inst. 88, 1560–1570 (1996).

  126. 126.

    et al. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J. Natl Cancer Inst. 88, 1550–1559 (1996).

  127. 127.

    et al. Serum 25-hydroxyvitamin D, dietary calcium intake, and distal colorectal adenoma risk. Nutr. Cancer 39, 35–41 (2001).

  128. 128.

    et al. Vitamin D receptor activity and prevention of colonic hyperproliferation and oxidative stress. Food Chem. Toxicol. 40, 1191–1196 (2002).

  129. 129.

    , , , & Dairy products, calcium and prostate cancer risk in Physicians' Health Study. Am. J. Clin. Nutr. 74, 549–554 (2001).

  130. 130.

    et al. Calcium and fructose intake in relation to risk of prostate cancer. Cancer Res. 58, 442–447 (1998).

  131. 131.

    et al. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br. J. Urol. 81, 730–734 (1998).

  132. 132.

    , , & Serum selenium and subsequent risk of prostate cancer. Cancer Epidemiol. Biomarkers Prev. 9, 883–887 (2000).

  133. 133.

    et al. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J. Natl Cancer Inst. 90, 1184–1185 (1998).

  134. 134.

    et al. SELECT: the next prostate cancer prevention trial. Selenum and Vitamin E Cancer Prevention Trial. J. Urol. 166, 1311–1315 (2001).

  135. 135.

    et al. Selected micronutrients and oral and pharyngeal cancer. Int. J. Cancer 86, 122–127 (2000).

  136. 136.

    et al. Role of macronutrients, vitamins and minerals in the aetiology of squamous-cell carcinoma of the oesophagus. Int. J. Cancer 86, 626–631 (2000).

  137. 137.

    , & Diet and cancer prevention. Europ. J. Cancer 37, 948–965 (2001).This review covers the evidence for a diet and cancer relationship, including the topics of vegetables and fruits, dietary fibre, micronutrients, phytochemicals, dietary fat, anthropometry/physical activity and alcohol. It also discusses the emerging evidence of gene–nutrient interactions and future directions.

  138. 138.

    , , & Insulin: a novel factor in carcinogenesis. Am. J. Med. Sci. 323, 140–145 (2002).

  139. 139.

    IARC International Agency for Research on Cancer, WHO. Weight Control and Physical Activity (IARC Press, Lyon, 2002).

  140. 140.

    Epidemiology of breast cancer. Lancet Oncol. 2, 133–140 (2001).

  141. 141.

    Obesity, cancer links prompt new recommendations. J. Natl Cancer Inst. 93, 901–902 (2001).

  142. 142.

    Role of phytochemicals in prevention and treatment of prostate cancer. Epidemiol. Rev. 23, 102–105 (2001).

  143. 143.

    & Dietary intake, dietary patterns, and changes with age: an epidemiolgical perspective. J. Gerontol. A. Biol. Sci. Med. Sci. 56, 65–80 (2001).

  144. 144.

    Analysis of: National Health and Nutrition Examination Survey III 1988–1994 Public-Use Data Files (National Center for Health Statistics, Hyattsville, Maryland).

  145. 145.

    The metabolic tune up: metabolic harmony and disease prevention. J. Nutr. (in the press).

  146. 146.

    et al. Lack of association between the C677T MTHFR polymorphism and colorectal hyperplasic polyps. Cancer Epidemiol. Biomarkers Prev. 9, 427–433 (2000).

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This work was supported by grants from the National Foundation for Cancer Research, the US Department of Energy, the Wheeler Fund for the Biological Sciences at the University of California Berkeley, the Ellison Medical Foundation and the National Institute of Environmental Health Sciences Center. We thank L. Gold and J. Nides for their many useful comments.

Author information


  1. Nutrition Genomics Center, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way, Oakland, California 94609-1673, USA.

    • Bruce N. Ames
    •  & Patricia Wakimoto


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Corresponding author

Correspondence to Bruce N. Ames.



Dietary intake of a vitamin or mineral at a level that is less than 50% of the recommended daily allowance — as distinguished from acute deficiency. For example, acute vitamin C deficiency causes scurvy.


(RDA). The dietary-intake level that is sufficient to meet the daily nutrient requirements of nearly all healthy individuals in a defined group.


An epidemiological study design in which individuals are selected based on the presence (case) or absence (control) of disease. Well-designed case–control studies require that the two groups are derived from the same population.


An epidemiological study design in which individuals with known characteristics (such as occupational exposure, smoking and exercise) are enrolled and followed over time for specific outcomes. The rate of cancer (or other disease) in the exposed population is compared to that in the unexposed population.


A retrospective analysis of the results from different studies, making certain assumptions, to reach a conclusion that is based on the pooled data.


These occur because behaviour-related variables of interest tend to cluster. An exposure (for example, vegetable consumption) might be of interest in protecting against a particular cancer. However, if smokers eat fewer vegetables than non-smokers, we might falsely attribute a risk reduction to vegetables that is really owing to the fact that a higher proportion of vegetable-eaters are non-smokers. Confounding factors can be controlled for by separating the smokers and the non-smokers and asking whether the vegetable–cancer association is seen in both groups, or by more sophisticated, but conceptually similar, statistical techniques.


Often called a clinical trial or experimental study, an epidemiological analysis of a hypothesized cause–effect relationship that is performed by modifying a supposed causal factor, such as lack of vitamin C consumption, in a population.


Occurs in individuals that describe events (such as exposures, diseases and pregnancy outcome) of the past in a non-comparable manner. It is primarily a problem in case–control studies when that presence of the disease in one group might result in differential recall (for example, of alcohol consumption or dietary behaviour) between the cases and controls.


A technique that uses electrophoresis of immobilized single cells to measure DNA strand breaks.


The number of years of tobacco use, multiplied by the number of packs per day. For example, 1 pack year is 20 cigarettes per day for 1 year, 40 cigarettes per day equals 2 pack years.


A genetic disorder and the most common form of iron overload disease, which is characterized by iron deposition in the liver and other tissues as a result of a small increase in intestinal iron absorption over many years. It most often affects white northern Europeans: 1 in 8–12 is a carrier of the abnormal gene, and men are five times more likely to be diagnosed with haemochromotosis than women.

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