Epidemiology of Cancer and Other Systemic Effects Associated with the Use of Smokeless Tobacco

Abstract

Persons who use chewing tobacco and snuff experience an increased risk of oral cancer. Because of the pharmacologic properties of nicotine and other constituents of smokeless tobacco, there is also concern that smokeless tobacco products may lead to cardiovascular diseases as well. The relatively few human population studies to date conflict with respect to whether smokeless tobacco use elevates cardiovascular risk factors or leads to cardiovascular disease or death from cardiovascular causes. Hemoglobin adducts to carcinogens present in smokeless tobacco products are measurable in the blood of smokeless tobacco users, indicating that smokeless-tobacco-related carcinogens circulate throughout the body. This prompts a concern that smokeless tobacco may increase risks of other cancers as well. The evidence to date from epidemiologic studies indicates no relationship between smokeless tobacco and bladder cancer, but there is suggestive evidence linking smokeless tobacco use to prostate cancer risk. Only single studies have been conducted of some cancers, and inconsistencies among studies of the same cancer site have been reported. Molecular epidemiologic studies may help identify markers of malignant transformation in smokeless tobacco users that may help in early intervention to prevent or ameliorate the consequences of oral cancer. Further studies are needed to determine more clearly the cardiovascular and non-oral cancer risks potentially associated with smokeless tobacco use.

Keywords

Tobacco smokeless mouth neoplasms cardiovascular diseases epidemiology nicotine other cancers.

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References

Advisory Committee to the Surgeon General ( 1986). The health consequences of using smokeless tobacco. Bethesda, MD: National Institutes of Health, NIH Publ. No. 86-2874.

Benowitz NL (1986). The human pharmacology of nicotine. In: Research advances in alcohol and drug problems. Vol. 9. Capell HD , Glaser FB , Israel Y , Kalant H , Schmidt W , Sellers EM , et al., editors. New York : Plenum Press, pp. 1-52.

Benowitz NL (1988). Sodium intake from smokeless tobacco. New Engl J Med 319:873-874.

Benowitz NL , Prochet H. , Sheiner L. , Jacob P. III (1988). Nicotine absorption and cardiovascular effects with smokeless tobacco use: Comparison with cigarettes and nicotine gum. Clin Pharmacol Ther 44:23-28.

Benowitz NL , Jacob P. III , Yu L. (1989). Daily use of smokeless tobacco: systemic effects . Ann Intern Med 111:112-116.

Blot WJ , McLaughlin JK , Winn DM , Austin DF , Greenberg RS , Preston-Martin S. , et al. (1988). Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 48:3282-3287.

Blot WJ , Devesa SS , McLaughlin JK , Fraumeni JF Jr (1994). Oral and pharyngeal cancers. In: Trends in cancer incidence and mortality. Doll R , Fraumeni JF Jr , Muir CS , editors. Plainview, NY: Cold Spring Harbor Laboratory Press, pp. 23-42.

Bolinder GM , Ahlborg BO , Lindell JH (1992). Use of smokeless tobacco: blood pressure elevation and other health hazards found in a large-scale population survey. J Intern Med 232:327-334.

Bolinder G. , Alfredsson L. , Englund A. , de Faire U. (1994). Smokeless tobacco use and increased cardiovascular mortality among Swedish construction workers. Am J Public Hlth 84:399-404.

10.

Brennan JA , Boyle JO , Koch WM , Goodman SN , Hruban RH , Eby YJ , et al. (1995). Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck. N Engl J Med 332 :712-717.

11.

Chow WH , McLaughlin JK , Menck HR , Mack TM ( 1994). Risk factors for extrahepatic bile duct cancers: Los Angeles County, California (USA). Cancer Causes Control 5:267-272.

12.

Devesa SS , Blot WJ , Stone BJ , Miller BA , Tarone RE , Fraumeni JF Jr (1995). Recent cancer trends in the United States. J Natl Cancer Inst 87:175-182.

13.

Eliasson M. , Asplund K. , Eurin P-E. , Lundblad D. (1995). Relationship of cigarette smoking and snuff dipping to plasma fibrinogen, fibrinolytic variables and serum insulin: The Northern Sweden MONICA study. Atherosclerosis 113:41-53.

14.

Giovino GA , Schooley MW , Zhu B-P. , Chrismon JH , Tomar SL , Peddicord JP , et al. (1994). Surveillance for selected tobacco-use behaviors-United States, 1900-1994. In: CDC surveillance summaries, November 18, 1994. Morbid Mortal Wkly Rep 43(55-3): 1-43.

15.

Giraud DW , Martin HD , Driskell JA (1995). Erythrocyte and plasma B-6 vitamin concentrations of long-term tobacco smokers, chewers, and nonusers. Am J Clin Nutr 62:104-109.

16.

Greenblatt MS , Bennett WP , Hollstein M. , Harris CC (1994). Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 54:4855-4878.

17.

Hayes RB , Pottern LM , Swanson GM , Liff JM , Schoenberg JB , Greenberg RS , et al. (1994). Tobacco use and prostate cancer in Blacks and Whites in the United States. Cancer Causes Control 5:221-226.

18.

Hecht SS , Carmella SG , Foiles PG , Murphy SE (1994). Biomarkers for human uptake and metabolic activation of tobacco-specific nitrosamines. Cancer Res 54(Suppl):1912s-1917s.

19.

Heineman EF , Zahm SH , McLaughlin JK , Vaught JB (1995). Increased risk of colorectal cancer among smokers: results of a 26-year follow-up of US veterans and a review. Int J Cancer 59:728-738.

20.

Heuch I. , Kvale G. , Jacobsen BK , Bjelke E. (1983). Use of alcohol, tobacco and coffee, and risk of pancreatic cancer. Br J Cancer 48:637-643.

21.

Hsing AW , McLaughlin JK , Schuman LM , Bjelke E. , Gridley G. , Wacholder S. , et al. (1990). Diet, tobacco use, and fatal prostate cancer: results from the Lutheran Brotherhood cohort study. Cancer Res 50:6836-6840.

22.

Hsing AW , McLaughlin JK , Hrubec Z. , Blot WJ , Fraumeni JF Jr (1991). Tobacco use and prostate cancer: 26 year follow-up of US veterans. Am J Epidemiol 133:437-441.

23.

Huhtasaari F. , Asplund K. , Lundberg V. , Stegmayr B. , Wester PO (1992). Tobacco and myocardial infarction: is snuff less dangerous than cigarettes? Br Med J 305:1252-1256.

24.

Idris AM , Ahmed HM , Malik Moa (1995). Toombak dipping and cancer of the oral cavity in the Sudan: A case-control study. Int J Cancer 63:477-480.

25.

Idris AM , Ahmed HM , Mucktar BI , Gadir AF , El-Behir El (1995). Descriptive epidemiology of oral neoplasms in Sudan 1970-1985 and the role of toombak. Int J Cancer 61:155-158.

26.

International Agency for Research on Cancer ( 1985). IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans: Tobacco habits other than smoking; betel-quid and areca-nut chewing; and some related nitrosamines. Vol. 37. Lyon, France: International Agency for Research on Cancer, p. 116.

27.

Kaugars GE , Riley WT , Brandt RB , Bums JC , Svirsky JA (1992). The prevalence of oral lesions in smokeless tobacco users and an evaluation of risk factors. Cancer 70:2579-2585.

28.

Lindquist R. , Nilsson B. , Eklund G. , Gahrton G. (1987). Increased risk of developing acute leukemia after employment as a painter. Cancer 60:1378-1384.

29.

Mommsen S. , Aagaard J. (1983). Tobacco as a risk factor in bladder cancer. Carcinogenesis 4:335-338.

30.

Murrah VA , Gilchrist EP , Moyer MP (1993). Morphologic and growth effects of tobacco-associated chemical carcinogens and smokeless tobacco extracts on human oral epithelial cells in culture. Oral Surg Oral Med Oral Pathol 75:323-332.

31.

Muscat JE , Hoffmann D. , Wynder EL (1995). The epidemiology of renal cell carcinoma: a second look. Cancer 75:2552-2557.

32.

National Institutes of Health (1986). Health implications of smokeless tobacco use. National Institutes of Health consensus development conference statement. Vol. 6, No. 1. Bethesda, MD: National Institutes of Health.

33.

Nordgren P. , Ramstrom L. (1990). Commentary: Moist snuff in Sweden-tradition and evolution. Br J Addiction 85:1107-1112.

34.

Office on Smoking and Health (1993). Use of smokeless tobacco among adults-United States, 1991 (published erratum appears in Morbid Mortal Wkly Rep 42:382, 1993). NCCDPHP, CDCP and Division of Health Interview Statistics, NCHS, CDCP. Morbid Mortal Wkly Rep 42:263-266.

35.

Persson P-G. , Hellers G. , Ahlbom A. (1993). Use of oral moist snuff and inflammatory bowel disease. Int J Epidemiol 22:1101-1103.

36.

Pitot HC (1993). The molecular biology of carcinogenesis. Cancer 72:962-970.

37.

Robertson PB (1997). Clinical and pathological oral effects of smokeless tobacco use. Adv Dent Res 11 :307-312.

38.

Schectman G. , Byrd JC , Gruchow HW (1989). The influence of smoking on vitamin C status in adults. Am J Public Hlth 79:158-162.

39.

Schiffman MH , Brinton LA (1995). The epidemiology of cervical carcinogenesis. Cancer 76(Suppl 10):1888-1901.

40.

Siegel D. , Benowitz N. , Ernster VL , Grady DG , Hauck WW (1992). Smokeless tobacco, cardiovascular risk factors, and nicotine and cotinine levels in professional baseball players. Am J Public Hlth 82:417-421.

41.

Silverman S. , Gorsky M. , Lozada F. (1984). Oral leukoplakia and malignant transformation: A follow-up study of 257 patients. Cancer 53:563-568.

42.

Slattery ML , Schumacher MC , West DW , Robison LM (1988). Smoking and bladder cancer: the modifying effect of cigarettes on other factors. Cancer 61:402-408.

43.

Spitz MR , Fueger JJ , Goepfert H. , Hong WK , Newell GR (1988). Squamous cell carcinoma of the upper aero-digestive tract: a case comparison analysis. Cancer 61:203-208.

44.

Squier CA (1986). Penetration of nicotine and nitrosonornicotine across porcine oral mucosa. J Appl Toxicol 6:123-128.

45.

Stegmayr B. , Johansson I. , Huhtasaari F. , Moser U. , Asplund K. (1992). Use of smokeless tobacco and cigarettes-Effects on plasma levels of antioxidant vitamins. Int J Vit Nutr Res 63:195-200.

46.

Sterling TD , Rosenbaum WL , Weinkam JJ (1992). Analysis of the relationship between smokeless tobacco and cancer based on data from the National Mortality Followback Survey . J Clin Epidemiol 45:223-231.

47.

Stockwell HG , Lyman GH (1986). Impact of smoking and smokeless tobacco on the risk of cancer of the head and neck. Head Neck Surg 9:104-110.

48.

Tucker LA (1989). Use of smokeless tobacco, cigarette smoking, and hypercholesterolemia. Am J Public Hlth 79:1048-1050.

49.

White BA , Antczak-Bouckoms A. (1995). Improving oral health through systemic reviews and meta-analysis. In: Disease prevention and oral health promotion . Cohen LK , Gift HC , editors. Copenhagen: Munksgaard , pp. 455-479.

50.

Williams RR , Horm JW ( 1977). Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of patients: interview study from the Third National Cancer survey. J Natl Cancer Inst 58:525-547.

51.

Winn DM ( 1992). Surveillance of and knowledge about cancer associated with smokeless tobacco use. In: Smokeless tobacco or health: An international perspective. Bethesda, MD: National Cancer Institute, National Institutes of Health. NIH Publ. No. 92-3461, pp. 11-18.

52.

Winn DM , Blot WJ , Shy CM , Pickle LW , Toledo A. , Fraumeni JF Jr (1981). Snuff dipping and oral cancer among women in the southern United States. N Engl J Med 304:745-749.

53.

Wood MW , Medina JE , Thompson GC , Houck JR (1994). Accumulation of the p53 tumor-suppressor gene product in oral leukoplakia. Otolaryngol Head Neck Surg 111:758-763.

54.

Yeudall WA (1992). Human papillomaviruses and oral neoplasia. Oral Oncol, Eur J Cancer 28(B):61-66.

55.

Zaridze DG , Blettner M. , Trapeznikov NN , Kuvshinov JP , Matiakin EG , Poljakov BP , et al. (1985). Survey of a population with a high incidence of oral and oesophageal cancer. Int J Cancer 36:153-158.

56.

Zaridze DG , Safaev RD , Belitsky GA , Brunnemann KD , Hoffmann D. (1991). Carcinogenic substances in Soviet tobacco products . In: Relevance to human cancer of N-nitroso compounds, tobacco smoke and mycotoxins. O'Neill IK , Chen J , Bartsch H , editors. Lyon, France: International Agency for Research on Cancer, pp. 485-488.