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Tobacco-related carcinogenesis in head and neck cancer

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Abstract

Head and neck cancer (head and neck squamous cell carcinoma (HNSCC)) is a devastating disease. Patients require intensive treatment that is often disfiguring and debilitating. Those who survive are often left with poor speech articulation, difficulties in chewing and swallowing, and cosmetic disfigurement, as well as loss of taste. Furthermore, given that HNSCC survivors are frequently disabled and unable to return to work, the economic and societal costs associated with HNSCC are massive. HNSCC is one of many cancers that are strongly associated with tobacco use. The risk for HNSCC in smokers is approximately ten times higher than that of never smokers, and 70–80% of new HNSCC diagnoses are associated with tobacco and alcohol use. Tobacco products have been used for centuries; however, it is just within the last 60–70 years that we have developed an understanding of their damaging effects. This relatively recent understanding has created a pathway towards educational and regulatory efforts aimed at reducing tobacco use. Understanding the carcinogenic components of tobacco products and how they lead to HNSCC is critical to regulatory and harm reduction measures. To date, nitrosamines and other carcinogenic agents present in tobacco products have been associated with cancer development. The disruption of DNA structure through DNA adduct formation is felt to be a common mutagenic pathway of many carcinogens. Intense work pertaining to tobacco product constituents, tobacco use, and tobacco regulation has resulted in decreased use in some parts of the world. Still, much work remains as tobacco continues to impart significant harm and contribute to HNSCC development worldwide.

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References

  1. Argiris, A., Karamouzis, M. V., Raben, D., & Ferris, R. L. (2008). Head and neck cancer. Lancet, 371(9625), 1695–1709. doi:10.1016/s0140-6736(08)60728-x.

    Article  CAS  PubMed  Google Scholar 

  2. Ridge, J. (2016). Head and neck tumors. http://www.cancernetwork.com/cancer-management/head-and-neck-tumors.

  3. Global Burden of Disease Cancer, C, Fitzmaurice, C., Allen, C., Barber, R. M., Barregard, L., Bhutta, Z. A., et al. (2017). Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncology, 3(4), 524–548. doi:10.1001/jamaoncol.2016.5688.

    Article  Google Scholar 

  4. Tobacco smoke and involuntary smoking (2004). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 83, 1–1438.

  5. Borio, G. (2004). Tobacco timeline. http://archive.tobacco.org/History/Tobacco_History.html.

  6. Doll, R., & Hill, A. B. (1950). Smoking and carcinoma of the lung; preliminary report. British Medical Journal, 2(4682), 739–748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Doll, R., & Hill, A. B. (1952). A study of the aetiology of carcinoma of the lung. British Medical Journal, 2(4797), 1271–1286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Doll, R., & Hill, A. B. (1954). The mortality of doctors in relation to their smoking habits; a preliminary report. British Medical Journal, 1(4877), 1451–1455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hammond, E. C., & Horn, D. (1954). The relationship between human smoking habits and death rates: a follow-up study of 187,766 men. Journal of the American Medical Association, 155(15), 1316–1328.

    Article  CAS  PubMed  Google Scholar 

  10. The 1964 report on smoking and health. https://profiles.nlm.nih.gov/ps/retrieve/Narrative/NN/p-nid/60. Accessed 24 Jan 2017.

  11. Office on Smoking and Health, N. C. f. C. D. P. a. H. P. History of the surgeon generals reports on smoking and health. https://www.cdc.gov/tobacco/data_statistics/sgr/history/. Accessed 24 Jan 2017.

  12. Medicine, T. I. o (2007). Ending the tobacco problem: a blueprint for the nation. The National Academic Press.

  13. Office on Smoking and Health, N. C. f. C. D. P. a. H. P. Current cigarette smoking among adults in the United States. https://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/.

  14. Data, G. H. O Prevalance of tobacco smoking. Accessed 24 Jan 2017.

  15. Organization, W. H (2006). Tobacco: deadly in any form or disguise. World Health Organization.

  16. Franck, C., Budlovsky, T., Windle, S. B., Filion, K. B., & Eisenberg, M. J. (2014). Electronic cigarettes in North America: history, use, and implications for smoking cessation. Circulation, 129(19), 1945–1952. doi:10.1161/circulationaha.113.006416.

    Article  PubMed  Google Scholar 

  17. Rigotti, N. A. (2015). e-cigarette use and subsequent tobacco use by adolescents: new evidence about a potential risk of e-cigarettes. JAMA, 314(7), 673–674. doi:10.1001/jama.2015.8382.

    Article  CAS  PubMed  Google Scholar 

  18. Zhou, J., Michaud, D. S., Langevin, S. M., McClean, M. D., Eliot, M., & Kelsey, K. T. (2013). Smokeless tobacco and risk of head and neck cancer: evidence from a case-control study in New England. International Journal of Cancer, 132(8), 1911–1917. doi:10.1002/ijc.27839.

    Article  CAS  PubMed  Google Scholar 

  19. Ng, M., Freeman, M. K., Fleming, T. D., Robinson, M., Dwyer-Lindgren, L., Thomson, B., et al. (2014). Smoking prevalence and cigarette consumption in 187 countries, 1980–2012. JAMA, 311(2), 183–192. doi:10.1001/jama.2013.284692.

    Article  CAS  PubMed  Google Scholar 

  20. Smokeless tobacco and public health: a global perspective (2014). (NIH Publication No. 14-7983): U.S. Department of Health and Human Services. Centers for Disease Control and Prevention and National Institutes of Health.

  21. Siddiqi, K., Shah, S., Abbas, S. M., Vidyasagaran, A., Jawad, M., Dogar, O., et al. (2015). Global burden of disease due to smokeless tobacco consumption in adults: analysis of data from 113 countries. BMC Medicine, 13, 194. doi:10.1186/s12916-015-0424-2.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Coelho, K. R. (2012). Challenges of the oral cancer burden in India. J Cancer Epidemiol, 2012, 701932. doi:10.1155/2012/701932.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hashibe, M., Brennan, P., Benhamou, S., Castellsague, X., Chen, C., Curado, M. P., et al. (2007). Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Journal of the National Cancer Institute, 99(10), 777–789. doi:10.1093/jnci/djk179.

    Article  PubMed  Google Scholar 

  24. Khariwala, S. S., Carmella, S. G., Stepanov, I., Fernandes, P., Lassig, A. A., Yueh, B., et al. (2013). Elevated levels of 1-hydroxypyrene and N′-nitrosonornicotine in smokers with head and neck cancer: a matched control study. Head & Neck, 35(8), 1096–1100. doi:10.1002/hed.23085.

    Article  Google Scholar 

  25. Winn, D. M., Lee, Y. C., Hashibe, M., & Boffetta, P. (2015). The INHANCE consortium: toward a better understanding of the causes and mechanisms of head and neck cancer. Oral Diseases, 21(6), 685–693. doi:10.1111/odi.12342.

    Article  CAS  PubMed  Google Scholar 

  26. Wyss, A., Hashibe, M., Chuang, S. C., Lee, Y. C., Zhang, Z. F., Yu, G. P., et al. (2013). Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. American Journal of Epidemiology, 178(5), 679–690. doi:10.1093/aje/kwt029.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wyss, A. B., Hashibe, M., Lee, Y. A., Chuang, S. C., Muscat, J., Chen, C., et al. (2016). Smokeless tobacco use and the risk of head and neck cancer: pooled analysis of US studies in the INHANCE Consortium. American Journal of Epidemiology. doi:10.1093/aje/kww075.

  28. Hashibe, M., Hunt, J., Wei, M., Buys, S., Gren, L., & Lee, Y. C. (2013). Tobacco, alcohol, body mass index, physical activity, and the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian (PLCO) cohort. Head & Neck, 35(7), 914–922. doi:10.1002/hed.23052.

    Article  Google Scholar 

  29. Hashibe, M., Brennan, P., Chuang, S. C., Boccia, S., Castellsague, X., Chen, C., et al. (2009). Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiology, Biomarkers & Prevention, 18(2), 541–550. doi:10.1158/1055-9965.epi-08-0347.

    Article  CAS  Google Scholar 

  30. Dal Maso, L., Torelli, N., Biancotto, E., Di Maso, M., Gini, A., Franchin, G., et al. (2016). Combined effect of tobacco smoking and alcohol drinking in the risk of head and neck cancers: a re-analysis of case-control studies using bi-dimensional spline models. European Journal of Epidemiology, 31(4), 385–393. doi:10.1007/s10654-015-0028-3.

    Article  CAS  PubMed  Google Scholar 

  31. Khariwala, S. S., Hatsukami, D., & Hecht, S. S. (2012). Tobacco carcinogen metabolites and DNA adducts as biomarkers in head and neck cancer: potential screening tools and prognostic indicators. Head & Neck, 34(3), 441–447. doi:10.1002/hed.21705.

    Article  Google Scholar 

  32. Hecht, S. S. (1998). Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosamines. Chemical Research in Toxicology, 11(6), 559–603. doi:10.1021/tx980005y.

    Article  CAS  PubMed  Google Scholar 

  33. Balbo, S., James-Yi, S., Johnson, C. S., O'Sullivan, M. G., Stepanov, I., Wang, M., et al. (2013). (S)-N′-Nitrosonornicotine, a constituent of smokeless tobacco, is a powerful oral cavity carcinogen in rats. Carcinogenesis, 34(9), 2178–2183. doi:10.1093/carcin/bgt162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yuan, J. M., Koh, W. P., Murphy, S. E., Fan, Y., Wang, R., Carmella, S. G., et al. (2009). Urinary levels of tobacco-specific nitrosamine metabolites in relation to lung cancer development in two prospective cohorts of cigarette smokers. Cancer Research, 69(7), 2990–2995. doi:10.1158/0008-5472.can-08-4330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Yuan, J. M., Knezevich, A. D., Wang, R., Gao, Y. T., Hecht, S. S., & Stepanov, I. (2011). Urinary levels of the tobacco-specific carcinogen N′-nitrosonornicotine and its glucuronide are strongly associated with esophageal cancer risk in smokers. Carcinogenesis, 32(9), 1366–1371. doi:10.1093/carcin/bgr125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Khariwala, S. S., Carmella, S. G., Stepanov, I., Bandyopadhyay, D., Nelson, H. H., Yueh, B., et al. (2015). Self-reported tobacco use does not correlate with carcinogen exposure in smokers with head and neck cancer. Laryngoscope, 125(8), 1844–1848. doi:10.1002/lary.25290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hecht, S. S. (2003). Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nature Reviews. Cancer, 3(10), 733–744. doi:10.1038/nrc1190.

    Article  CAS  PubMed  Google Scholar 

  38. Lacko, M., Braakhuis, B. J., Sturgis, E. M., Boedeker, C. C., Suarez, C., Rinaldo, A., et al. (2014). Genetic susceptibility to head and neck squamous cell carcinoma. International Journal of Radiation Oncology, Biology, Physics, 89(1), 38–48. doi:10.1016/j.ijrobp.2013.09.034.

    Article  CAS  PubMed  Google Scholar 

  39. Riaz, N., Morris, L. G., Lee, W., & Chan, T. A. (2014). Unraveling the molecular genetics of head and neck cancer through genome-wide approaches. Genes Dis, 1(1), 75–86. doi:10.1016/j.gendis.2014.07.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lao, Y., Yu, N., Kassie, F., Villalta, P. W., & Hecht, S. S. (2007). Analysis of pyridyloxobutyl DNA adducts in F344 rats chronically treated with (R)- and (S)-N′-nitrosonornicotine. Chemical Research in Toxicology, 20(2), 246–256. doi:10.1021/tx060208j.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hecht, S. S., Spratt, T. E., & Trushin, N. (1988). Evidence for 4-(3-pyridyl)-4-oxobutylation of DNA in F344 rats treated with the tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N′-nitrosonornicotine. Carcinogenesis, 9(1), 161–165.

    Article  CAS  PubMed  Google Scholar 

  42. Wang, M., Cheng, G., Sturla, S. J., Shi, Y., McIntee, E. J., Villalta, P. W., et al. (2003). Identification of adducts formed by pyridyloxobutylation of deoxyguanosine and DNA by 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone, a chemically activated form of tobacco specific carcinogens. Chemical Research in Toxicology, 16(5), 616–626. doi:10.1021/tx034003b.

    Article  CAS  PubMed  Google Scholar 

  43. Stepanov, I., Muzic, J., Le, C. T., Sebero, E., Villalta, P., Ma, B., et al. (2013). Analysis of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing DNA adducts in human exfoliated oral mucosa cells by liquid chromatography-electrospray ionization-tandem mass spectrometry. Chemical Research in Toxicology, 26(1), 37–45. doi:10.1021/tx300282k.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hecht, S. S., Stepanov, I., & Carmella, S. G. (2016). Exposure and metabolic activation biomarkers of carcinogenic tobacco-specific nitrosamines. Accounts of Chemical Research, 49(1), 106–114. doi:10.1021/acs.accounts.5b00472.

    Article  CAS  PubMed  Google Scholar 

  45. Zhang, S., Wang, M., Villalta, P. W., Lindgren, B. R., Upadhyaya, P., Lao, Y., et al. (2009). Analysis of pyridyloxobutyl and pyridylhydroxybutyl DNA adducts in extrahepatic tissues of F344 rats treated chronically with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Chemical Research in Toxicology, 22(5), 926–936. doi:10.1021/tx900015d.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ma, B., Ruszczak, C., Jain, V., Khariwala, S. S., Lindgren, B., Hatsukami, D. K., et al. (2016). Optimized liquid chromatography nanoelectrospray-high-resolution tandem mass spectrometry method for the analysis of 4-hydroxy-1-(3-pyridyl)-1-butanone-releasing DNA adducts in human oral cells. Chemical Research in Toxicology, 29(11), 1849–1856. doi:10.1021/acs.chemrestox.6b00254.

    Article  CAS  PubMed  Google Scholar 

  47. Chen, A. M., Chen, L. M., Vaughan, A., Sreeraman, R., Farwell, D. G., Luu, Q., et al. (2011). Tobacco smoking during radiation therapy for head-and-neck cancer is associated with unfavorable outcome. International Journal of Radiation Oncology, Biology, Physics, 79(2), 414–419. doi:10.1016/j.ijrobp.2009.10.050.

    Article  PubMed  Google Scholar 

  48. Hatcher, J. L., Sterba, K. R., Tooze, J. A., Day, T. A., Carpenter, M. J., Alberg, A. J., et al. (2016). Tobacco use and surgical outcomes in patients with head and neck cancer. Head & Neck, 38(5), 700–706. doi:10.1002/hed.23944.

    Article  Google Scholar 

  49. Marin, V. P., Pytynia, K. B., Langstein, H. N., Dahlstrom, K. R., Wei, Q., & Sturgis, E. M. (2008). Serum cotinine concentration and wound complications in head and neck reconstruction. Plastic and Reconstructive Surgery, 121(2), 451–457. doi:10.1097/01.prs.0000297833.53794.27.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Samir S. Khariwala.

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Jethwa, A.R., Khariwala, S.S. Tobacco-related carcinogenesis in head and neck cancer. Cancer Metastasis Rev 36, 411–423 (2017). https://doi.org/10.1007/s10555-017-9689-6

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