Genotoxic and Carcinogenic Effect of Gutkha: A Fast-growing Smokeless Tobacco

Document Type : Review Article(s)

Authors

1 Assistant Professor, Department of Oral Maxillofacial Pathology, Government Dental College and Hospital, Jaipur, Rajasthan, India

2 Assistant Professor, Department of Oral Medicine and Radiology, Vyas Dental College and Hospital, Jodhpur, Rajasthan, India

3 Assistant Professor, Department of Dental Materials, Government Dental College and Hospital, Jaipur, Rajasthan, India

Abstract

Oral cancer is a highly lethal disease and one of the most debilitating and disfiguring of all malignancies in the world. According to Global Adult Tobacco Survey (GATS) 2010 report, 60% of tobacco users in India use only smokeless tobacco. Among 206 million smokeless tobacco users, 65.1 million are consuming gutkha. In recent years, gutkha is recognized as a life threatening disorder with the serious health consequences. The aim of this review is to increase the attention to complete ban of tobacco use, awareness, knowledge, and beliefs of public about the harms of not only gutkha but also all other tobacco products and also to promote the intentions to quit the habits.

Keywords


  1. Warnakulasuriya S, Sutherland G, Scully C. Tobacco, oral cancer, and treatment of dependence. Oral Oncol 2005; 41(3): 244-60.
  2. Reddy KS, Gupta RC. Report on tobacco control in India. Geneva, Switzerland: World Health Organization; 2004.
  3. Raute LJ, Sansone G, Pednekar MS, Fong GT, Gupta PC, Quah AC, et al. Knowledge of health effects and intentions to quit among smokeless tobacco users in India: Findings from the International Tobacco Control Policy Evaluation (ITC) India Pilot Survey. Asian Pac J Cancer Prev 2011; 12(5): 1233-8.
  4. Bathi RJ, Parveen S, Burde K. The role of gutka chewing in oral submucous fibrosis: A case-control study. Quintessence Int 2009; 40(6): e19-e25.
  5. Khanna S. The interaction between tobacco use and oral health among tribes in central India. Tob Induc Dis 2012; 10(1): 16.
  6. Gupta PC. Mouth cancer in India: A new epidemic? J Indian Med Assoc 1999; 97(9): 370-3.
  7. Boffetta P, Hecht S, Gray N, Gupta P, Straif K. Smokeless tobacco and cancer. Lancet Oncol 2008; 9(7): 667-75.
  8. Chaturvedi P. Gutka consumption. Br Dent J 2009; 206(8): 397.
  9. Global Adult Tobacco Survey (GATS) India, 2009-2010. New Delhi, India: Ministry of Health and Family Welfare, Government of India; 2010.
  10. Sarkar BK, Reddy KS. Priorities for tobacco control research in India. Addiction 2012; 107(12): 2066-8.
  11. Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines. IARC Monogr Eval Carcinog Risks Hum 2004; 85: 1-334.
  12. Warad S, Chaudhari HL, Ashok N, Jenifer HD. Clinical evaluation of gutkha chewing and pattern of bone loss in periodontitis. World J Dent 2014; 5(4): 199-203.
  13. Kyaing NN, Islam MA, Sinha DN, Rinchen S. Social, economic and legal dimensions of tobacco and its control in South-East Asia region. Indian J Public Health 2011; 55(3): 161-8.
  14. Mishra GA, Kulkarni SV, Gupta SD, Shastri SS. Smokeless tobacco use in Urban Indian women: Prevalence and predictors. Indian J Med Paediatr Oncol 2015; 36(3): 176-82.
  15. Bhonsle RB, Murti RB, Gupta PC. Tobacco habit in India. In: Gupta PC, Hamner JE, Murti PR, Editors. Control of tobacco-related cancers and other diseases: Proceedings of an international symposium, January 15-19, 1990, TIFR, Bombay. Oxford, UK: Oxford University Press, 1992. p. 25-46.
  16. Madani AH, Dikshit M, Bhaduri D. Risk for oral cancer associated to smoking, smokeless and oral dip products. Indian J Public Health 2012; 56(1): 57-60.
  17. Joshi PS, Prashant MC, Nagpal N, Patil AA, Ahuja R, Mathur V. Gutkha addiction: Nicotine dependence or a conditioned reflex? J Int Oral Health 2015; 7(Suppl 2): 45-7.
  18. RamIal G, Reddy V, Venkateshwarulu N, Shalini K, Patil R. Significance of oral brush cytology of oral mucosal lesions in gutkha chewers: A prospective study. J IndAcad Oral Med Radiol 2011; 23(4): 539-42.
  19. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Smokeless Tobacco and Some Tobacco-specific N-nitrosamines. Geneva, Switzerland: World Health Organization; 2007.
  20. Asma S, Backinger C, Smokeless Tobacco fact sheets. Proceedings of the 3rd International Conference on Smokeless Tobacco; 2002 Sep. 22-25. Stockholm, Sweden.
  21. Gangwal K. What is gutka? [Online]. [cited 2001]; Available from: URL:
  22. http://www.antigutkha.com/whatisgutkha.html. 2018.
  23. Gupta PC. Gutka: A major new tobacco hazard in India. Tob Control 1999; 8(2): 134.
  24. Gupta PC, Ray CS, Sinha DN, Singh PK. Smokeless tobacco: A major public health problem in the SEA region: A review. Indian J Public Health 2011; 55(3): 199-209.
  25. Kharat P, Shailendra S, Bhushan P. Gutka-a malignant entity seeks benign exit in India. J Evol Med Dent Sci 2013; 2(3): 245-51.
  26. Mukherjee K, Hadaye RS. Gutkha consumption and its determinants among secondary school male students. Indian J Community Med 2006; 31(3): 177.
  27. Changrani J, Gany FM, Cruz G, Kerr R, Katz R. Paan and Gutka use in the united states: A pilot study in Bangladeshi and Indian-Gujarati immigrants in New York City. J Immigr Refug Stud 2006; 4(1): 99-110.
  28. Benowitz NL. Nicotine and SmokelessTobacco. Ca-A Cancer Journal for Clinicians 1988; 38(4): 244-7.
  29. Anwar S, Williams SA, Scott-Smith J, Sage H, Baweja S, Singal M, et al. A comparison of attitudes and practices of gutka users and non-users in Chitrakoot, India. A pilot. Prim Dent Care 2005; 12(1): 5-10.
  30. Nichter M, Nichter M, Van Sickle D. Popular perceptions of tobacco products and patterns of use among male college students in India. Soc Sci Med 2004; 59(2): 415-31.
  31. Bhisey RA. Chemistry and toxicology of smokeless tobacco. Indian J Cancer 2012; 49(4): 364-72.
  32. Hoffmann D, Brunnemann KD, Prokopczyk B, Djordjevic MV. Tobacco-specific N-nitrosamines and Areca-derived N-nitrosamines: Chemistry, biochemistry, carcinogenicity, and relevance to humans. J Toxicol Environ Health 1994; 41(1): 1-52.
  33. Chaudhry K. Is pan masala-containing tobacco carcinogenic? Natl Med J India 1999; 12(1): 21-7.
  34. Stepanov I, Hecht SS, Ramakrishnan S, Gupta PC. Tobacco-specific nitrosamines in smokeless tobacco products marketed in India. Int J Cancer 2005; 116(1): 16-9.
  35. Centers for Disease Control and Prevention (US), National Center for Chronic Disease Prevention and Health Promotion (US), Office on Smoking and Health (US). How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta, GA: Centers for Disease Control and Prevention; 2010.
  36. Xue J, Yang S, Seng S. Mechanisms of cancer induction by tobacco-specific NNK and NNN. Cancers (Basel) 2014; 6(2): 1138-56.
  37. Bhisey RA. Genotoxicity and carcinogenicity of pan masala: A review. Proc Indian Natl Sci Acad B 2000; 66(1): 1-2.
  38. Nair U, Bartsch H, Nair J. Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: A review of agents and causative mechanisms. Mutagenesis 2004; 19(4): 251-62.
  39. Jeng JH, Lan WH, Hahn LJ, Hsieh CC, Kuo MY. Inhibition of the migration, attachment, spreading, growth and collagen synthesis of human gingival fibroblasts by arecoline, a major areca alkaloid, in vitro. J Oral Pathol Med 1996; 25(7): 371-5.
  40. Jeng JH, Chang MC, Hahn LJ. Role of areca nut in betel quid-associated chemical carcinogenesis: Current awareness and future perspectives. Oral Oncol 2001; 37(6): 477-92.
  41. Norton SA. Betel: Consumption and consequences. J Am Acad Dermatol 1998; 38(1): 81-8.
  42. Nair UJ, Friesen M, Richard I, MacLennan R, Thomas S, Bartsch H. Effect of lime composition on the formation of reactive oxygen species from areca nut extract in vitro. Carcinogenesis 1990; 11(12): 2145-8.
  43. Chadha P, Yadav JS. Studies on the genotoxicity of gutkha. Int J Hum Genet 2011; 11(4): 277-82.
  44. Nair J, Ohshima H, Malaveille C, Friesen M, O'Neill IK, Hautefeuille A, et al. Identification, occurrence and mutagenicity in Salmonella typhimurium of two synthetic nitroarenes, musk ambrette and musk xylene, in Indian chewing tobacco and betel quid. Food Chem Toxicol 1986; 24(1): 27-31.
  45. Willis DN, Popovech MA, Gany F, Hoffman C, Blum JL, Zelikoff JT. Toxicity of gutkha, a smokeless tobacco product gone global: Is there more to the toxicity than nicotine? Int J Environ Res Public Health 2014; 11(1): 919-33.
  46. Gupta PC, Warnakulasuriya S. Global epidemiology of areca nut usage. Addict Biol 2002; 7(1): 77-83.
  47. Ali FM, Aher V, Prasant MC, Bhushan P, Mudhol A, Suryavanshi H. Oral submucous fibrosis: Comparing clinical grading with duration and frequency of habit among areca nut and its products chewers. J Cancer Res Ther 2013; 9(3): 471-6.
  48. Dwivedi S, Goel A, Mandhani A, Khattri S, Pant KK. Tobacco exposure may enhance inflammation in prostate carcinoma patients: An explorative study in north Indian population. Toxicol Int 2012; 19(3): 310-8.
  49. Dwivedi S, Goel A, Khattri S, Mandhani A, Sharma P, Pant KK. Tobacco exposure by various modes may alter proinflammatory (IL-12) and anti-inflammatory (IL-10) levels and affects the survival of prostate carcinoma patients: An explorative study in North Indian population. Biomed Res Int 2014; 2014: 158530.
  50. Guengerich FP. Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem Res Toxicol 2001; 14(6): 611-50.
  51. Hang B. Formation and repair of tobacco carcinogen-derived bulky DNA adducts. J Nucleic Acids 2010; 2010: 709521.
  52. Jyoti Sen D, Dadida C, Dhliwayo P. Gutkha as a charm in in-vitro & harm in in-vivo: A devil in disguise. World J Pharm Pharm Sci 2014; 3(11): 1400-14.
  53. Bagchi M, Balmoori J, Bagchi D, Stohs SJ, Chakrabarti J, Das DK. Role of reactive oxygen species in the development of cytotoxicity with various forms of chewing tobacco and pan masala. Toxicology 2002; 179(3): 247-55.
  54. Coppe JP, Boysen M, Sun CH, Wong BJ, Kang MK, Park NH, et al. A role for fibroblasts in mediating the effects of tobacco-induced epithelial cell growth and invasion. Mol Cancer Res 2008; 6(7): 1085-98.
  55. Jyoti S, Khan S, Naz F, Rahul, Ali F, Siddique YH. Assessment of DNA damage by panmasala, gutkha chewing and smoking in buccal epithelial cells using alkaline single cell gel electrophoresis (SCGE). Egyptian Journal of Medical Human Genetics 2013; 14(4): 391-4.
  56. Gupta PC, Ray CS, Murti PR, Sinha DN. Rising incidence of oral cancer in Ahmedabad city. Indian J Cancer 2014; 51(Suppl 1): S67-S72.
  57. Mahapatra S, Kamath R, Shetty BK, Binu VS. Risk of oral cancer associated with gutka and other tobacco products: a hospital-based case-control study. J Cancer Res Ther 2015; 11(1): 199-203.
  58. Chadda RK, Sengupta SN. Tobacco use by Indian adolescents. Tob Induc Dis 2002; 1(1): 8.
  59. Gupta PC, Subramoney S. Smokeless tobacco use and risk of stillbirth: A cohort study in Mumbai, India. Epidemiology 2006; 17(1): 47-51.
  60. World Health Organization. Review of areca (Betel) nut and tobacco use in the pacific: A technical report. Geneva, Switzerland: WHO; 2012.
  61. Nayak SS. Risk factors associated with gutkha addiction: An empirical study in Cuttack city of Odisha. J Sociology Soc Anth 2011; 2(2): 89-95.
  62. Nair S, Schensul JJ, Begum S, Pednekar MS, Oncken C, Bilgi SM, et al. Use of smokeless tobacco by Indian women aged 18-40 years during pregnancy and reproductive years. PLoS One 2015; 10(3): e0119814.
  63. Javed F, Chotai M, Mehmood A, Almas K. Oral mucosal disorders associated with habitual gutka usage: a review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109(6): 857-64.
  64. BBC News. Health, Chewing tobacco cancer warning [Online]. [cited 1999]; Available from: URL: http:/news.bb.co.uk/1/hi/health/398630.stm
  65. Varughese A. Gutka- A Silent Killer [Online]. [cited 2003]; Available from: URL:
  66. file:///C:/Users/Hamid%20Computer%20Group/Desktop/ref%2064.pdf
  67. Vinod Kumar Tikoo S, Dhawan A, Pattanayak RD, Chopra A. Assessment of pattern and profile of substance use among children in India. New Delhi, India: National Drug Dependence Treatment Centre; 2013.
  68. Mishra GA, Pimple SA, Shastri SS. An overview of the tobacco problem in India. Indian J Med Paediatr Oncol 2012; 33(3): 139-45.
  69. Winn DM. Smokeless Tobacco and Cancer: The epidemiologic evidence. CA: A Cancer Journal for Clinicians 1988; 38(4): 236-43.
  70. Weintraub JA, Burt BA. Periodontal effects and dental caries associated with smokeless tobacco use. Public Health Rep 1987; 102(1): 30-5.
  71. Siegel D, Benowitz N, Ernster VL, Grady DG, Hauck WW. Smokeless tobacco, cardiovascular risk factors, and nicotine and cotinine levels in professional baseball players. Am J Public Health 1992; 82(3): 417-21.
  72. Monson AL, Beaulieu JA. Smokeless tobacco use and knowledge among university students. The Internet Journal of Allied Health Sciences and Practice 2011; 9(1): 1-9.
  73. Nilsson R. Possible carcinogenicity of smokeless tobacco. Int J Cancer 2006; 118(6): 1582-3.
  74. Chaturvedi P. Gutka or areca nut chewer's syndrome. Indian J Cancer 2009; 46(2): 170-2.
  75. Nigam NK, Aravinda K, Dhillon M, Gupta S, Reddy S, Srinivas RM. Prevalence of oral submucous fibrosis among habitual gutkha and areca nut chewers in Moradabad district. J Oral Biol Craniofac Res 2014; 4(1): 8-13.
  76. Ambika L, Keluskar V, Hugar S, Patil S. Prevalence of oral mucosal lesions and variations in Indian public school children. Braz J Oral Sci 2011; 10(4): 288.
  77. Duggirala TL, Marthala M, Gannepalli A, Podduturi SR. Oral submucous fibrosis in children: Report of three cases and review. J Indian Acad Oral Med Radiol 2015; 27(1): 105-11.
  78. Kumar S, Parmar G, Saiyed HN. Nut and tobacco chewing. Br Dent J 2004; 197(6): 292.
  79. Chaturvedi P. Gutka consumption. Br Dent J 2009; 206(8): 397.
  80. Mallikarjuna R, Gangwal RR, Shanthraj SL, Dave B. Report of gutkha (smokeless tobacco) use in children aged 10-12 years. BMJ Case Reports 2013; 2012: 008319.
  81. Kumar A, Mythri S, Hegde S, Rajesh KS. Effect of chewing gutkha on oral hygiene, gingival and periodontal status. J Oral Health Res 2012; 3(3): 26-31.
  82. Malagi S, Hegde S, Kashyup R, Maiya AK, Mohan S. Effects of smokeless tobacco on gingival and periodontal status in adults: A case control study. Univ Res J Dent 2013; 3(2): 47-53.
  83. Ahmad MS, Ali SA, Ali AS, Chaubey KK. Epidemiological and etiological study of oral submucous fibrosis among gutkha chewers of Patna, Bihar, India. J Indian Soc Pedod Prev Dent 2006; 24(2): 84-9.
  84. Nayak AG, Chhaparwal Y, Pai KM. The hazards of gutka chewing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 110(5): 548-9.
  85. Gupta PC, Ray CS. Epidemiology of betel quid usage. Ann Acad Med Singapore 2004; 33(4 Suppl): 31-6.
  86. Patel S, Rendell H, Maudgal S, Oswal K. Tobacco industry tactics with advertisements at the point of sale in Mumbai. Indian J Cancer 2013; 50(3): 245-9.
  87. Jakszyn P, Gonzalez CA. Nitrosamine and related food intake and gastric and oesophageal cancer risk: A systematic review of the epidemiological evidence. World J Gastroenterol 2006; 12(27): 4296-303.
  88. News analysis. Tobacco Control 2011; 20(2): 89-92.
  89. Dhumal GG, Gupta PC. Assessment of gutka ban in Maharashtra: Findings from a focus group discussion. Int J Head Neck Surg 2013; 4(3): 115-8.
  90. Shetty P. Pan masala plus tobacco is equal to Gutka square-new formulation of tobacco in India after the Gutka ban. Asian Pac J Cancer Prev 2014; 15(24): 10991-2.
  91. Health Consequences of Smokeless Tobacco Use. In: Hatsukami DK, Zeller M, Gupta PC, Editors. Smokeless Tobacco and Public Health: A Global Perspective. Bethesda, MD: Centers for Disease Control and Prevention and National Institutes of Health; 2014.
  92. Babu S, Sesikeran B, Bhat RV. Oral fibrosis among teenagers chewing tobacco, areca nut, and Pan masala. Lancet 1996; 348(9028): 692.
  93. Pershagen G. Smokeless tobacco. Br Med Bull 1996; 52(1): 50-7.
  94. Hecht SS, Carmella SG, Murphy SE, Riley WT, Le C, Luo X, et al. Similar exposure to a tobacco-specific carcinogen in smokeless tobacco users and cigarette smokers. Cancer Epidemiol Biomarkers Prev 2007; 16(8): 1567-72.
  95. Chang MC, Chiang CP, Lin CL, Lee JJ, Hahn LJ, Jeng JH. Cell-mediated immunity and head and neck cancer: With special emphasis on betel quid chewing habit. Oral Oncol 2005; 41(8): 757-75.
  96. Nair S, Schensul JJ, Bilgi S, Kadam V, D'Mello S, Donta B. Local responses to the Maharashtra gutka and pan masala ban: A report from Mumbai. Indian J Cancer 2012; 49(4): 443-7.
  97. Naik NS. Tobacco: National and international perspective. Karnataka, India: Centre For Multi Disciplinary Development Research; 1999.
  98. Pimple S, Gunjal S, Mishra GA, Pednekar MS, Majmudar P, Shastri SS. Compliance to Gutka ban and other provisons of COTPA in Mumbai. Indian J Cancer 2014; 51(Suppl 1): S60-S66.