CHEMOPREVENTION OF CANCER

Epidemiologic studies have provided evidence that populations who consume large quantities of fruits and vegetables in their diets have a lower risk of cancer. It is hypothesized that

carotenoids that are converted to vitamin A in the liver and intestine may be important in the primary chemoprevention of cancer. [86] The following mechanisms are proposed for the

anticarcinogenic effects of carotenoids and retinoids:

• Retinoic acid promotes differentiation of mucus-secreting epithelial tissues. Supplementation of the diet with beta-carotene and retinol is hypothesized to reverse squamous

metaplasia and preneoplastic lesions in the respiratory tract of cigarette smokers and workers exposed to asbestos.

• Fruits and vegetables provide antioxidants such as betacarotene, vitamins C and E, and selenium that prevent oxidative damage to DNA.

• Vitamin A can enhance immune responses; other retinoids may modulate inflammatory reactions that are potential sources of reactive oxygen and nitrogen intermediates.

Notwithstanding such theoretical considerations, clinical studies on the role of vitamin A supplementation and cancer risk have failed to provide clear answers. Clinical trials using betacarotene

and retinyl palmitate as primary preventive agents against lung cancer were terminated because the participants showed an excess of lung cancers and increased mortality. On the

other hand, 13-cis-retinoic acid was effective in prevention of secondary squamous cell carcinomas of the head and neck region. These apparently conflicting results are not easily

explained; however, there are multiple chemical forms of retinoids that alter gene expression, cell proliferation, differentiation, and apoptosis by binding to six different nuclear receptors.

Some retinoids are associated with significant toxicity, including dry skin, conjunctivitis, and hypertriglyceridemia. Until the biochemical and molecular mechanisms of action of

individual retinoids and other antioxidants are understood, it is unwise to recommend dietary supplements for the primary chemoprevention of cancer. However, a diet rich in fruits,

vegetables, and unprocessed grains that is low in fat and animal protein has been associated with a decreased risk of cardiovascular disease and some types of cancer.[84]

High animal fat intake combined with low fiber intake has been implicated in the causation of colon cancer. The most convincing explanation for these associations is as follows: high fat

intake increases the level of bile acids in the gut, which in turn modifies intestinal flora, favoring the growth of microaerophilic bacteria. The bile acids or bile acid metabolites produced by

these bacteria might serve as carcinogens or promoters. The protective effect of a high-fiber diet might relate to (1) increased stool bulk and decreased transit time, which decrease the

exposure of mucosa to putative offenders, and (2) the capacity of certain fibers to bind carcinogens and thereby protect the mucosa.

Attempts to document these theories in clinical and experimental studies have, on the whole, led to contradictory results.

Thus, we must conclude that, despite many tantalizing trends and proclamations by "diet gurus," to date there is no definite proof that diet can cause or protect against cancer. Nonetheless,

concern persists that carcinogens lurk in things as pleasurable as a juicy steak and rich ice cream.

References

1. Levy BS, Wegman DH: Occupational health—an overview. In Levy BS, et al. (eds): Occupational Health. Recognizing and Preventing Work-Related Disease and Injury, 4th ed.

Philadelphia, Lippincott Williams & Wilkins, 2000, pp 3–13.

2. Carpenter DO, et al: Understanding the human health effects of chemical mixtures. Environ Health Perspect 110 (suppl A):25, 2002.

3. Minna JD, et al: Focus on lung cancer. Cancer Cell 1:49, 2002.

4. Hodgson E: Introduction to toxicology. In Hodgson E, Levi PE (eds): Textbook of Modern Toxicology. Stamford, CT, Appleton & Lange, 1997, pp 1–25.

5. Hodgson E, Levi PE: Absorption and distribution of toxicants. In Hodgson E, Levi PE (eds): A Textbook of Modern Toxicology. Stamford, CT, Appleton & Lange, 1997, pp 27–56.

6. Nebert DW, Russell DW: Clinical importance of the cytochromes P450. Lancet 360:1155, 2002.

7. Perera FP: Environment and cancer: who are susceptible? Science 278:1068, 1997.

8. Nordberg J, Arnér ESJ: Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radical Biol Med 31:1287, 2001.

9. Bolger PM, Schwetz, BA: Mercury and Health. N Engl J Med 347:1735, 2002.

10. Clarkson TW: The three modern faces of mercury. Environ Health Perspect 110 (suppl 1):11, 2002.

11. Fellows JL, et al: Annual smoking-attributable mortality, years of potential life lost, and economic costs—United States, 1995–1999. MMWR 51:300, 2002.

12. Wiencke JK, Kelsey KT: Teen smoking, field cancerization, and a "critical period" hypothesis for lung cancer susceptibility. Environ Health Perspect 110:555, 2002.

13. Pinkerton KE, et al: Interaction of tobacco smoking with occupational and environmental factors. In Harber PH, et al (eds.): Occupational and Environmental Respiratory Disease. St.

Louis, Mosby, 1996, pp 827–835.

14. Hanrahan JP, Weiss ST: Environmental tobacco smoke. In Harber PH, et al (eds): Occupational and Environmental Respiratory Disease. St. Louis, Mosby, 1996, pp 767–783.

15. Lieber CS: Medical disorders of alcoholism. N Engl J Med 333:1058, 1995.

16. Tsukamoto H, Lu SC: Current concepts in the pathogenesis of alcoholic liver injury. FASEB J 15:1335, 2001.

17. Thackray H, Tifft C: Fetal alcohol syndrome. Pediatr Rev 22(2):47, 2001.

18. Montesano R, Hill J: Environmental causes of human cancers. Eur J Cancer 37:S67, 2001.

19. Cami J, et al.: Drug addiction. N Engl J Med 349:975, 2003.

20. Hyman SE: A 28-year-old man addicted to cocaine. JAMA 286:2586, 2001.

21. Lange RA, Hillis LD: Cardiovascular complications of cocaine. N Engl J Med 345:351, 2001.

22. Kantak KM: Vaccines against drugs of abuse: a viable treatment option? Drugs 63:341, 2003.

23. Reneman L, et al: Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons. Lancet 358:1864, 2001.

24. Lazarou J, et al: Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies JAMA 279:1200, 1998.

25. Philips KA, et al: Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA 286:2270, 2001.

26. Evans WE, Johnson JA: Pharmacogenomics: the inherited basis for interindividual differences in drug response. Annu Rev Genomics Hum Genet 2:9, 2001.

27. Dahl M-L: Cytochrome P450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing? Clin Pharmacokinet 41:453, 2002.

28. Ernst E: The risk-benefit profile of commonly used herbal therapies: ginkgo, St. John's wort, ginseng, echinacea, saw palmetto, and kava. Ann Intern Med 136:42, 2002.

29. Davidson NE, Helzlsouer KJ: Good news about oral contraceptives. N Engl J Med 346:2078, 2002.

30. Marchbanks PA, et al: Oral contraceptives and the risk of breast cancer. N Engl J Med 346:2025, 2002.

31. Nelson HID, et al: Postmenopausal hormone replacement therapy: scientific review. JAMA 288:872, 2002.

32. Grodstein F, Clarkson TB, Manson JE: Understanding divergent data on postmenopausal hormone therapy. N Engl J Med. 348:645, 2003.

33. Berde CB, Sethna NF: Analgesics for the treatment of pain in children. N Engl J Med 347:1094, 2002.

34. Bascom R, et al: Health effects of outdoor air pollution. Am J Respir Crit Care Med 153:3, 477, 1996.

35. Pope CA: Epidemiology of fine particulate air pollution and human health: biologic mechanisms and who's at risk? Environ Health Perspect 108 (suppl 4):713, 2000.

36. Lambert WE, Samet JM: Indoor air pollution. In Harber P, et al (eds): Occupational and Environmental Respiratory Disease. St. Louis, Mosby, 1996, pp 784–807.

37. Morgan KT: A brief review of formaldehyde carcinogenesis in relation to rat nasal pathology and human health risk assessment. Toxicol Pathol 25:291, 1997.

38. Samet JM, Eradze GR: Radon and lung cancer risk: taking stock at the millennium. Environ Health Perspect 108 (suppl 4):635, 2000.

39. Billings CH, Howard P: Asbestos exposure, lung cancer and asbestosis. Moraldi Arch Dis 55:151, 2000.

40. Manning CB, Vallyathan V, Mossman BT: Diseases caused by asbestos: mechanisms of injury and disease development. Intl Immunopharmacol 2:191, 2002.

41. Menzies D, Bourbeau J: Building-related illnesses. N Engl J Med 337:1524, 1997.

42. Mastrangelo G, et al: Polycyclic aromatic hydrocarbons and cancer in man. Environ Health Perspect 104:1166, 1996.

43. Kelleher P, et al: Inorganic dust pneumonias: the metal-related parenchymal disorders. Environ Health Perspect 108 (suppl 4):685, 2000.

44. Fischbein A: Occupational and environmental lead exposure. In Rom WN (ed.): Environmental and Occupational Medicine, 2nd ed. Boston, Little, Brown, 1992, pp 735–758.

45. Rogan WJ, Ware JH: Exposure to lead in children—how low is low enough? N Engl J Med 348:1515, 2003.

46. Goyer RA: Results of lead research: prenatal exposure and neurological consequences. Environ Health Perspect 104:1050, 1996.

47. Costa M, et al: Molecular mechanisms of nickel carcinogenesis. Environ Health Perspect 102 (Suppl 3):127, 1994.

48. Goldman LR: Environmental health and its relationship to occupational health. In Levy BS, et al. (eds): Occupational Health. Recognizing and Preventing Work-Related Disease and

Injury, 4th ed. Philadelphia, Lippincott Williams & Wilkins, 2000, pp 51–96.

49. Moline JM, et al: Exposure to hazardous substances and male reproductive health: a research framework. Environ Health Perspect 108:803, 2000.

50. Schantz SL, Widholm JJ: Cognitive effects of endocrine-disrupting chemicals in animals. Environ Health Perspect 109:1197, 2001.

51. Huff J, et al: Carcinogenicity of TCDD: experimental, mechanistic, and epidemiologic evidence. Annu Rev Pharmacol Toxicol 34:343, 1994.

52. Mettler FA, Voelz GL: Major radiation exposure—what to expect and how to respond. N Engl J Med 346:1554, 2002.

53. Upton AC: Ionizing radiation. In Craighead JE (ed): Pathology of Environmental and Occupational Disease. St. Louis, Mosby, 1996, pp 205–214.

54. Karanjawla ZE et al.: Supplementary oxygen metabolism causes chromosome breaks and is associated with neuronal apoptosis observed in double stranded DNA strand repair mutants.

Curr Biol 12:397, 2002.

55. Smith ML, Fornace AJ Jr: Mammalian DNA damage-inducible genes associated with growth arrest and apoptosis. Mutat Res 340:109, 1996.

56. Paris F, et al: Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science 293:293, 2001.

57. Belka C, et al: Radiation induced CNS toxicity—molecular and cellular mechanisms. Brit J Cancer 85:1233, 2001.

58. Johnston CJ, et al: Radiation-induced pulmonary fibrosis: examination of chemokine and chemokine receptor families. Radiation Res 157:256, 2002.

59. Murnane JP: Role of induced genetic instability in the mutagenic effects of chemicals and radiation. Mutat Res 367:11, 1996.

60. Greenblatt MS, et al: Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 54:4855, 1994.

61. Rittie L, Fisher GJ: UV light-induced signal cascades and skin aging. Aging Res Rev 1:705, 2002.

62. Cleaver JE, Crowley E: UV damage, DNA repair and skin carcinogens. Front Biosci 7:1024, 2002.

63. Cleary SF: Electromagnetic energy. In Craighead JE (ed): Pathology of Environmental and Occupational Disease. St. Louis, Mosby, 1996, pp 215–228.

64. Ahlbom A, et al: Review of the epidemiologic literature on EMF and health. Environ Health Perspect 109 (Suppl 6):911, 2001.

65. Adey WR, et al: Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats exposed to frequency-modulated microwave fields. Cancer Res

60:1857, 2000.

66. Rivara FP, et al: Injury prevention. N Engl J Med 337:543, 613, 1997.

67. Rodricks JV, Jackson BA: Food constituents and contaminants. In Lippmann M (ed): Environmental Toxicants: Human Exposures and Their Health Effects. New York, Van Nostrand

Reinhold, 1992, pp 266–298.

68. Detsky AL, et al: Is this patient malnourished? JAMA 271:54, 1994.

69. Tisdale MJ: Biology of cachexia. J Natl Cancer Inst 89:1763, 1997.

70. Stephensen CB: Vitamin A, infection and immune function. Ann Rev Nutr 21:167, 2001.

71. Lips P: Hypervitaminosis A and fractures. N Engl J Med. 348:347, 2003.

72. Willett WC, Stampfer MJ: What vitamins should I be taking, Doctor? N Engl J Med 345:1819, 2001.

73. Tangpricha V, et al: Vitamin D insufficiency among free living healthy young adults. Am J Med 112:659, 2002.

74. Fairfield KM, Fletcher RH: Vitamins for chronic disease prevention in adults: scientific review. JAMA 287:3116, 2002.

75. Koshihara Y, et al: Vitamin K stimulates osteoblastogenesis and inhibits osteoclastogenesis in human bone marrow culture. J Endocrinol 176:339, 2003.

76. Branda RF: Folic acid deficiency. In Craighead JM (ed): Pathology of Environmental and Occupational Disease. St. Louis, Mosby, 1996, pp 170–174.

77. Lumley J, et al: Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. Cochrane Database of Systematic Reviews, June 1, 2002.

78. Marx J: Cellular warriors at the battle of the bulge. Science 299:846, 2003.

79. Klein S, Wadden T, Sugerman HJ: AGA technical review on obesity. Gastroenterol 123:882, 2002.

80. Lustig RH: The neuroendocrinology of obesity. Endocrinol Metab Clin North Am 30(3):765, 2001.

81. Cummings DE, Schwartz MW: Genetics and pathophysiology of human obesity: Annu Rev Med 54:453, 2003.

81A. Elmquist JK, Flier JS: The fat-brain axis enters a new dimension. Science 304:63, 2004.

82. Lakka HM, et al: The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288:2709, 2002.

83. List JF, Havener JF: Defective melanocortin 4 receptors in hyperphagia and morbid obesity. N Engl J Med 384:1160, 2003.

84. Calle EE, et al: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 348:1625, 2003.

85. Bucher HC, et al: N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med 112:298, 2002.

86. Hong WK, Sporn MB: Recent advances in chemoprevention of cancer. Science 278:1073, 1997.

Date: 2016-04-22; view: 769