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Paan Without Tobacco: an Independent Risk Factor for Oral Cancer

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Paan Without Tobacco: an Independent Risk Factor for Oral Cancer Int. J. Cancer: 86, 128–131 (2000) Publication of the International Union Against Cancer © 2000 Wiley-Liss, Inc. PAAN WITHOUT TOBACCO: AN INDEPENDENT RISK FACTOR FOR ORAL CANCER 1,2,3 4 5 2 3,6,7 2 Anwar MERCHANT * Syed S. M. HUSAIN , Mervyn HOSAIN , Fariyal F. FIKREE , Waranuch PITIPHAT , Amna Rehana SIDDIQUI , 4 8 4 3,6 9 Syed J. HAYDER , Syed M. HAIDER , Mubashir IKRAM , Sung-Kiang CHUANG and Shaikh A. SAEED 1Department of Nutrition, Harvard School of Public Health, Boston, MA, USA 2Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan 3Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA 4Department of Surgery, Aga Khan University, Karachi, Pakistan 5Department of Oral and Maxillofacial Surgery, Civil Hospital Karachi, Pakistan 6Department of Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, Boston, MA, USA 7Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand 8Department of Oral and Maxillofacial Surgery, Abbassi Shaheed Hospital, Karachi, Pakistan 9Department of Pharmacology, Aga Khan University, Karachi, Pakistan Oral cancer is the second most common cancer in women MATERIAL AND METHODS and the third most common in men in Pakistan. Tobacco is smoked and chewed extensively in Pakistan. Paan is a quid of Between July 1996 and March 1998, we recruited biopsy- piper betel leaf that contains areca nut, lime, condiment, proven primary cases of oral squamous-cell carcinoma, from Aga sweeteners, and sometimes tobacco, which is also used ex- Khan University Hospital (AKUH), Civil Hospital Karachi (CHK) tensively. We did this study to clarify the independent asso- and Abbassi Shaheed Hospital (ASH). All 3 hospitals are tertiary ciation of paan and oral cancer. Between July 1996 and March teaching centers located in Karachi, Pakistan. AKUH and CHK 1998, we recruited biopsy-proven, primary cases of oral squa- have attached undergraduate medical colleges. Patients attend all 3 mous-cell carcinoma, from 3 tertiary teaching centers in hospitals from all over the province. Sindh is Pakistan’s second Karachi, Pakistan, and controls pair-matched for age, gender, largest province, with a population of approximately 30 million. hospital and time of occurrence, excluding persons with a past or present history of any malignancy. There were 79 Karachi is the largest city in Sindh, with a multi-ethnic population cases and 149 controls. Approximately 68% of the cases were of 9.8 million according to the 1998 census. men, 49 years old on average, the youngest being 22 years old We pair-matched controls from patients who had been admitted and the eldest 80. People with oral submucous fibrosis were to the orthopedic and general surgical wards of the same hospital 19.1 times more likely to develop oral cancer than those at the same time as the corresponding case, were of the same sex, without it, after adjusting for other risk factors. People using and were aged within 5 years of the cases. We excluded as controls paan without tobacco were 9.9 times, those using paan with tobacco 8.4 times, more likely to develop oral cancer as persons with a past or present history of any malignancy. compared with non-users, after adjustment for other co- After obtaining verbal consent, a trained interviewer adminis- variates. This study identifies an independent effect of paan tered a structured, pre-tested, questionnaire in Urdu (the lingua without tobacco in the causation of oral cancer. Its findings franca of Pakistan), examined the mouth, and checked for the may be of significance in South Asian communities where presence of oral submucous fibrosis (OSMF) on cases and con- paan is used, and among health-care providers who treat trols. This was determined clinically by observation of blanching persons from South Asia. Int. J. Cancer 86:128–131, 2000. and by palpation for the presence of fibrous bands. The interviewer © 2000 Wiley-Liss, Inc. was clinically trained to check the clinical signs of the disease. In addition to socio-economic and demographic data, we also col- lected information on the use of cigarettes, bidis, hookah, naswar, Oral cancer is the second most common cancer in women and paan, areca nut, and alcohol. We defined users of naswar, paan or the third most common in men in Pakistan (Jafarey and Zaidi, areca nut as someone who had ever indulged in the habit daily for 1987). Tobacco, chewed or smoked, is a well-established cause of a month. Smokers were persons who had ever smoked cigarettes, oral squamous-cell carcinoma (Gupta et al., 1982; Jayant and Deo, bidis, hookah, cigar, or a pipe daily for at least one month. For 1986; Brennan et al., 1995). Alcohol, particularly in association each of the substances we asked the date of starting, current use or with tobacco, increases the risk of oral cancer. Approximately 40% date of quitting, and average quantity used per day. During anal- of men in Pakistan over the age of 15 years smoke cigarettes or bidis (locally cured tobacco rolled in a dry leaf) regularly (National Health Survey of Pakistan, 1997). Tobacco is chewed in Pakistan Definitions: Oral submucous fibrosis (OSMF), Progressive fibrosis of the as paan and as naswar. Paan consists of piper betel leaf containing oral mucosa resulting in limited mouth opening. Strongly associated with lime, areca nut, condiments, sweeteners and sometimes tobacco. It areca nut use; pre-cancerous. Paan without tobacco, Piper betel leaf con- taining lime, areca nut, condiments and sweeteners. It is chewed and held is chewed and held in the mouth like a quid. Naswar is a mixture in the mouth like a quid. Paan with tobacco, Piper betel leaf containing of tobacco and lime (Jayant and Deo, 1986). Areca nut without lime, areca nut, condiments, sweeteners and tobacco. It is chewed and held tobacco is suspected of being associated with oral cancer, but in the mouth like a quid. Naswar, Tobacco and lime mixture that is chewed epidemiological studies have not clearly demonstrated its indepen- and held in the mouth like a quid. Bidi, Locally cured tobacco rolled in a dent effect (Dave et al., 1992). A study has shown significantly dry leaf and smoked. Hookah, Hubble-bubble. A pipe for smoking tobacco more chromosomal aberrations, sister chromatid exchanges, and in which the smoke is filtered through water before inhalation. genomic damage among areca-nut users than among non-users, independently of tobacco use (Dave et al., 1992). But areca-nut Grant sponsor: Aga Khan University, Karachi. users, independently of tobacco use, are 100 times more likely to get oral submucous fibrosis, which is a pre-cancerous lesion of the mouth (Maher et al., 1994). A study from South Africa showed *Correspondence to: Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. Fax: ϩ1 617 increased risk of oral cancer from chewing areca nut, but the 432-2435. E-mail: [email protected] estimates were not adjusted for all important risk factors (van Wyk et al., 1993). We did this study to clarify the independent associ- ation of paan and oral cancer. Received 10 September 1999; Revised 16 November 1999 PAAN WITHOUT TOBACCO AND ORAL CANCER RISK 129 ysis, we combined persons reporting only areca nut with those TABLE I – COMPARISON OF THE DEMOGRAPHIC AND SOCIO-ECONOMIC consuming paan without tobacco, after evaluating them separately CHARACTERISTICS OF THE STUDY SUBJECTS, KARACHI, 1996–1998 and finding them similar. Case (n ϭ 79) Control (n ϭ 149) Characteristics We calculated the sample size to detect a difference in cases and Number % Number % controls, assuming that users of paan without tobacco were 4 times Hospital as likely to get oral cancer as those who did not chew paan, and AKU 32 40.5 44 29.5 that the prevalence of paan chewing in this population was 13%. Civil 38 48.1 89 59.7 With Epi-Info (Dean et al., 1994), we used the Bonferroni method, Abbasi 9 11.4 16 10.7 to be able to simultaneously evaluate risk factors. We took the Gender power to be 90% and the alpha error to be 1%. With a ratio of 2 Male 54 68.4 94 63.1 controls to 1 case, the sample size turned out to be 72 cases and Female 25 31.6 55 36.9 144 controls. Education Never attended school 40 51.9 72 48.3 The data were double-entered for verification in Epi-info. We Primary 11 13.9 20 13.4 did conditional logistic regression analysis (SAS, 1996) in which Middle 7 8.9 11 7.4 the outcome variable was presence of oral cancer. The predictor Secondary 10 12.7 18 12.1 variables included education, presence of oral submucous fibrosis, Higher 10 18.8 28 18.8 ever-use of naswar, of paan with tobacco, of paan without tobacco, Ethnicity ever-smoking of tobacco, ever-use of alcohol. We calculated Urdu speaking 40 50.6 70 47.0 matched odds ratios in the univariate analysis and considered Sindhi 13 16.5 28 18.8 ϭ Punjabi 4 5.1 16 10.7 variables that were significant at alpha 0.15 in this analysis for Balochi 9 11.4 15 10.1 further evaluation in the multivariate analysis. Pathan 4 5.1 9 6.0 We then added potentially confounding variables to the model Gujarati 7 8.9 4 2.7 and observed changes in the beta coefficients of the variables in the Other 1 1.3 3 2.0 core model. Potentially confounding variables, which made at least No response 1 1.3 4 2.7 10% change in the beta-coefficient estimate of one of the variables Religion in the core model, were considered as confounders and were added Islam 68 86.1 143 96.0 Christianity 1 1.3 3 2.0 in the final model.
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