Tobacco habits and risk of lung, oropharyngeal and oral cavity cancer: a population-based case-control study in Bhopal, India

Rajesh P Dikshit and Shiela Kanhere

Reprint requests to: Dr Rajesh Dikshit, Department of Pathology, Gandhi Medical College, Bhopal (MP), 462001, India.


    Abstract
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background Tobacco habits in India are unique and vary in different regions. Few studies, and none from central India, have reported on type of tobacco used and risk of the most common cancer types in India. We conducted a population-based case-control study to evaluate the risk of tobacco particularly bidi smoking and tobacco quid chewing on the most common cancer sites among males in Bhopal.

Methods In all, 163 lung, 247 oropharyngeal and 148 oral cavity cancer cases from the Population-Based Cancer Registry records and 260 controls randomly selected from a tobacco survey conducted in the Bhopal population formed the study population.

Results A significant risk of bidi and cigarette smoking with a dose-response relationship was observed for lung and oropharyngeal cancer. Tobacco quid chewing showed no risk for lung, marginally increased risk for oropharyngeal and about a sixfold increased risk for oral cavity cancer. Population-attributable risk per cent (PARP) was observed to be 82.7% and 71.6% for smokers for the development of lung and oropharyngeal cancer, while the same was found to be 66.1% for tobacco chewers for the development of oral cavity cancer.

Conclusions These data provide strong evidence that smoking bidi is even more hazardous than cigarette smoking in the development of lung and oropharyngeal cancer. An intervention study to prevent the use of tobacco will be useful in this population as it also underwent gas exposure due to a chemical accident in 1984.

Keywords Bidi smoking, tobacco quid chewing, lung cancer, oropharynx cancer, oral cavity cancer

Accepted 10 January 2000


    Introduction
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Lung, oropharyngeal and oral cavity cancer are the most common cancer sites observed by Indian registries.1 These cancer sites are causally related to the use of tobacco in different forms.2 In India, the use of tobacco is common in the form of chewing and smoking of bidis and cigarettes.3

Two studies are available from India on the role of bidi smoking in the development of lung cancer.4,5 A few studies, mainly from West Maharashtra and South India, have reported the risk of oropharyngeal and oral cavity cancer and smoking and oral use of tobacco,6,7,8 but no study has been reported from central India.

In the present study three cancer sites (lung, oropharynx and oral cavity) were investigated using a common protocol and data from the Bhopal Cancer Registry. The risk of tobacco use, particularly bidi smoking and chewing, was estimated for these three sites. A study on tobacco use in this population is particularly important as it suffered exposure to methyl-isocyanate gas due to a chemical accident in 1984 and thus is different from other parts of the world.


    Materials and Methods
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
The present study examines data for the three most common cancer sites in males (lung, oropharynx and oral cavity), collected by the Bhopal Population-Based Cancer Registry during the years 1986–1992.

The cancer cases were coded by four-digit International Classification of Diseases for Oncology (ICD-O) code.9 The cancer sites included under oropharynx were posterior third of tongue (141.0 and 141.6), soft palate (145.3), uvula (145.4), oropharynx (146.0–146.9), nasopharynx (147.0–147.9), and hypopharynx (148.0–149.0). The cancer sites included under oral cavity were lip (140.0–140.9), anterior two-thirds of tongue (141.1–141.5), gingivum (143.0–143.9), floor of mouth (144.0–144.9), cheek mucosa (145.0–145.2), hard-palate and retromolar area (145.5–145.9). A total of 260 controls were randomly sampled from a total of about 2500 males surveyed for tobacco habits in the Bhopal population. This tobacco survey was based on random samples from the voter list of the Bhopal municipal corporation area. The survey was conducted by the Bhopal cancer registry during 1989–1992. The controls were not matched for age with the cases, however, they were age-stratified and then randomly selected to follow the age distribution of cases.

The cases and controls were interviewed according to a precoded questionnaire. The subjects were asked about identification particulars, socioeconomic parameters, tobacco habits, and clinical history. The interview was conducted by three qualified social workers of the Cancer Registry staff. The cases for which detailed information about smoking or chewing history were not available were excluded from the study. Cases registered from death certificates were excluded. Similarly, the tongue not otherwise specified cases (141.9) were not included in the analysis. After exclusion, a total of 163 lung, 247 oropharyngeal and 148 oral cavity cancer cases were available for the analysis.

The data collected were compiled and quality checks were carried out. Age-adjusted odds ratio (OR) and 95% CI for the sites under study according to religion, educational status, smoking and chewing habits were estimated using unconditional multiple logistic regression models. The models were compared using the differences in deviance and in degrees of freedom. The result of variable of interest with and without confounding variable was tabulated. The effect of interaction between variable of interest and confounder were also obtained to understand the validity of adjustment. The dummy variable and linear dose-response model was compared for testing the extent to which the linear trend adequately explains the variation between the dose level.10 The population attributable risk and attributable risk of individuals exposed to exposure of interest were also estimated. For model fitting, the statistical program GLIM was used.11


    Results
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Table 1Go presents the distribution of socio-demographic, smoking and chewing habits for lung, oropharyngeal and oral cavity cancer cases and controls. Most of the cases and controls were Hindu. Of the controls, 51.5% never had formal education, while 53.4% of lung, 64% of oropharyngeal and 70.9% of oral cavity cancer cases had never attended the school. The habit of smoking and tobacco chewing was more common among cases than the controls.


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Table 1 Distribution of socio-demographical, smoking and chewing variables studied among lung, oropharyngeal and oral cavity cancer cases and controls
 
Religion and educational status did not appear to increase the risk of lung, oropharyngeal and oral cavity cancer after controlling for smoking and chewing habits (Table 2Go). As shown in Table 2Go, tobacco smokers showed increased risk for lung and oropharyngeal cancer but marginally increased risk for oral cavity cancer. Tobacco chewing showed about a sixfold increase in risk for oral cavity, marginally increased risk for cancer of the oropharynx and no increase in risk for lung cancer in comparison to non-tobacco chewers. There were only 16 subjects who had a history of chewing regularly without using tobacco. The estimates for relative risk, based on small numbers, showed increased risk for oral cavity cancer in comparison to non-chewers even after controlling for smoking habits.


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Table 2 Risk of lung, oropharyngeal and oral cavity cancer by religion, education, smoking and chewing habits
 
Table 3Go illustrates the risk of lung and oropharyngeal cancer according to the number of bidi and cigarettes smoked per day. The risk estimates for oral cavity cancer could not be estimated separately for bidi and cigarette smoking, as there were only six cigarette smokers among the oral cavity cancer cases. The risk of lung and oropharyngeal cancer increased with number of bidi as well as cigarettes smoked. This relationship seemed to be linear as observed departure from linear trend was not statistically significant at the 5% level.


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Table 3 Risk of lung and oropharyngeal cancer by type, and number of bidi/cigarette smoked per day
 
The multiplicative interaction between bidi and cigarette smoking was significant at the 5% level: the risk of bidi and cigarette smoking combined was observed to be 24.1 and 6.2 for lung and oropharyngeal cancer, respectively, in comparison to non-smokers of bidi and cigarettes. The risk of developing lung cancer (11.6/7.7 = 1.5) and oropharyngeal cancer (7.9/4.1 = 1.9) was higher for bidi smokers in comparison to cigarette smokers (Table 4Go).


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Table 4 Estimates of odds ratio (OR) for lung and oropharyngeal cancer among smokers of both bidi and cigarettes compared ton non-smokers of both. Adjusted for agea
 
As shown in Table 5Go, the risk of lung and oropharyngeal cancer increased approximately more than four and three times, respectively, within three levels of grouping done for duration of smoking of bidi/cigarettes. The risk of getting oral cavity cancer was 4.3 for those who had smoked for >30 years compared to non-smokers. The risk of >500 cumulative years of tobacco smoked compared to non-smokers was 67.6 for lung cancer, 23.0 for oropharyngeal cancer and 6.0 for oral cavity cancer. The lung cancer risk according to histological types among smokers compared to non-smokers shows that the risk is higher for squamous cell carcinoma. The OR estimates for small cell and oat cell carcinoma were based on small numbers and no convergence was obtained for this type. The risk among smokers by histological types was not estimated for oropharyngeal and oral cavity cancer as only one case of adenocarcinoma was reported for oropharyngeal cancer while for the oral cavity only squamous cell carcinomas were reported during the study period.


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Table 5 Risk of lung, oropharyngeal and oral cavity cancer by duration, cumulative years of smoking and histological types for smokers compared to non-smokers
 
Table 6Go presents the risk of oropharyngeal and oral cavity cancer according to number and duration of chewing tobacco quid compared to non-tobacco chewers. The same was not estimated for lung cancer as chewing tobacco quid was not observed to increase the risk of lung cancer. A linear dose-response relationship was observed between number of times tobacco quid were chewed per day and the risk of development of oral cavity cancer. The risk of oropharyngeal cancer was close to unity <=10 tobacco quid chewed per day but it was 3.6 for tobacco quid chewed >10 times per day in comparison to non-chewers of tobacco. The risk for oral cavity cancer increased about five times with increase in duration from 20 years to >30 years of chewing tobacco. A risk of 3.1 was observed for oropharyngeal cancer among tobacco quid chewers for >30 years. The trend was not linear for both the sites.


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Table 6 Risk of oropharyngeal and oral cavity cancer according to number (per day) and duration (in years) of chewing tobacco quids. Adjusted for age and smoking, reference category non-tobacco chewers
 
Table 7Go presents the joint effect of smoking and tobacco chewing on risk of oral cavity cancer. The multiplicative interaction although not significant at the 5% level, was almost significant at the 10% level ({chi}22 = 4.04; P {approx} 0.10). Tobacco quid chewing and bidi and/or cigarette smoking had a risk of 16.3 in comparison to non-smokers and non-chewers of tobacco for developing oral cavity cancer.


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Table 7 Joint effects of smoking and tobacco quid chewing on risk of oral cavity cancer
 

    Discussion
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
The motivation for examining the carcinogenic effects of tobacco smoking and chewing in this population was that smoking habits differ in India and in this region from other parts of the world. The habit of bidi smoking and ‘zarda’, a form of tobacco chewing, is peculiar to this region. Case ascertainment in the present study is based on Cancer Registry data and thus entailed high-quality diagnostic confirmation. The controls were randomly selected from a tobacco survey conducted in the same population. Although the controls were not selected concurrently with the cases, it seems unlikely that this will alter the risk estimates as the period of survey (1989–1992) was almost same as the recruitment of cases (1986–1992) for the study. Further, no anti-tobacco activities were organized during the study period to alter the prevalence of tobacco habits in this population.

Religion and educational status were not observed to be risk factors in the present study. A study of the association of religion and smoking habits with lung cancer likewise did not observe any excess risk for different religion.5 Both bidis and cigarettes were found to be independently associated with increased risk of lung and oropharynx cancer. Two previous studies on the risk of lung cancer among bidi smokers have shown conflicting results. Notani and Sanghavi,4 taking hospital controls, found a relative risk of 2.6, while Jussawalla and Jain,5 taking community controls, found a relative risk of 19.3 in comparison to non-smokers. Similar to the present study increased risk for oropharyngeal cancer among bidi smokers was observed in a previous study.6

The observed OR for bidi and cigarette smoking combined (OR = 24.1 for lung and OR = 6.2 for oropharynx) in comparison to non-smokers of both was much lower than expected, indicating that either mode of action is not multiplicative or those smoking both bidis and cigarettes are light smokers of each. The risk estimates further revealed that smoking bidi is even more hazardous than cigarette smoking in the development of lung and oropharyngeal cancer (Table 4Go).

The Indian bidi contains only a small amount of tobacco dust rolled in a dried leaf of tendu (Diospyrous malanoxylon) or Temburni tree (Diospyrous ebenum).12 In comparison to US cigarettes, the mainstream smoke of bidi contains a much higher concentration of several toxic agents such as hydrogen cyanide, carbon monoxide, ammonia, other volatile phenols, and carcinogenic hydrocarbons such as benz(a)anthracene and benzopyrene. Bidi also delivers more nicotine than Indian cigarettes. The nitrosonornicotine (NNN) and 4(methyl-nitrosoamino)-1-(3-pyridol) (NNK) level of bidi tobacco ranged from 6.2 to 12 µg/g compared with 1.3 to 58.0 µg/g in cigarette tobacco.13 Further, bidi smokers were found to take almost five puffs per minute compared to the cigarette smokers who smoked two puffs per minute.12 Thus, higher yields of tobacco-specific nitrosamines (TSNA) and higher puffing frequency among bidi smokers suggest that the finding of the present study, that the risk for development of lung and oropharyngeal cancer is higher among bidi smokers, is biologically plausible. The effect of smoking differed according to cell type of lung cancer. The risk was highest for squamous cell carcinoma. While the risk of smoking was lowest for developing adenocarcinoma, it was still high (OR = 3.9). These results are consistent with the result of other workers.14,15

Chewing tobacco contains a high level of TSNA.13 Of these, for NNK and its reduction product 4-(methyal(nitrosoamino)-1-1(3-pyridyl)-1-butanol) (NNAL) the major target organ is the lung, especially the peripheral part of the lung. This is independent of the route of admission, whether these procarcinogens are applied topically to the skin, taken orally or by intraperitoneal injection.16,17 These experimental studies suggest that tobacco chewing may also enhance the risk of lung cancer. The present study, however, did not observe any increased risk of tobacco chewing for lung cancer. The increased risk for oral cavity cancer among tobacco chewers is in accordance to that observed by other workers.7,8,18 These risk estimates in the present study could not be adjusted for the use of alcohol as history of alcohol use was not taken in the Cancer Registry proforma. However, this does not seem to alter the risk of tobacco chewing to a great extent. In India the prevalence of alcohol consumption particularly relative to tobacco chewing is low. Studies from India have not observed excess risk for oral cancer among alcohol users.7,8 The interaction model presented in Table 7Go gave an indication that the mode of action of tobacco quid chewing and smoking may not be multiplicative. It further indicated a decline in risk of chewing of tobacco with increased amount of tobacco smoked, this may be because heavy smokers chew less than light smokers.

In India cross-sectional surveys have shown that the percentage of people who chew betel quid without tobacco is small. In the present study also, based on small numbers, elevated risk was observed for oral cavity cancer among chewers not using tobacco, a finding similar to another study from south India.8

Tobacco consumption has decreased in many developed countries while in most developing countries it is still increasing. This may largely be due to the fact that relatively fewer studies have been reported from developing countries, including India, on the risk of cancer at different cancer sites due to the use of various forms of tobacco.19 In the present study it was estimated that the population attributable risk per cent (PARP) for smoking was quite high for lung (82.7%) and oropharyngeal cancer (71.6%). Similarly, the PARP was found to be 66.1% for tobacco chewers for development of oral cavity cancer. The attributable risk among smokers was observed to be 92% and 85% for lung and oropharyngeal cancer, respectively. The attributable risk for those who chewed tobacco was 84.4% for development of oral cavity cancer. This suggests that the high percentage of lung, oropharyngeal and oral cavity cancers in Bhopal could be prevented if tobacco habits were not started. Intervention studies encouraging quitting tobacco use have much relevance in Bhopal as in this population lungs are already damaged to some extent due to exposure to methyl isocynate gas as a result of the chemical disaster in December 1984. Even if gas exposure proves to be carcinogenic in future, by preventing the use of tobacco, a large number of cancer cases could be prevented.


    Acknowledgments
 
The authors would like to thank the staff of the Bhopal Cancer Registry. The helpful advice of Dr Matti Hakama and Dr Suvi Virtanen is gratefully acknowledged. The Bhopal Cancer Registry is a part of and funded by National Cancer Registry Programme of Indian Council of Medical Research.


    Notes
 
Population-Based Cancer Registry, Department of Pathology, Gandhi Medical College, Bhopal, India.


    References
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
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2 International Agency for Research on Cancer. Tobacco Smoking. Monographs on the evaluation of carcinogenic risk of chemicals to humans, Vol. 38. Lyon: IARC, 1985.

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