|Year : 2015 | Volume
| Issue : 2 | Page : 280-286
Analysis of various risk factors affecting potentially malignant disorders and oral cancer patients of Central India
Vidya Kadashetti1, Minal Chaudhary2, Swati Patil2, Madhuri Gawande2, KM Shivakumar3, Snehal Patil3, RC Pramod1
1 Department of Oral Pathology, Microbiology and Forensic Odontology, Krishna Institute of Medical Sciences University, Malkapur, Karad, Satara, India
2 Department of Oral Pathology, Microbiology and Forensic Odontology, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Medical Sciences University, Sawangi, Wardha, Maharashtra, India
3 Public Health Dentistry, School of Dental Sciences, Krishna Institute of Medical Sciences University, Malkapur, Karad, Satara, India
|Date of Web Publication||7-Jul-2015|
Oral Pathology and Microbiology, Forensic Odontology, School of Dental Sciences, Krishna Institute of Medical Sciences University, Malkapur, Karad, Satara - 415 539, Maharashtra
Source of Support: None, Conflict of Interest: None
Context: The use of tobacco/betel quid can alone lead to death. India is the fourth largest consumer of tobacco/betel quid in the world and the third-largest producer of tobacco/betel quid after China and Brazil.
Aims: A case-control study was carried out to assess the prevalence and various risk factors among potentially malignant disorders (PMD) and oral cancer patients of central India.
Settings and Design: A total of 100 clinically and histopathologically diagnosed PMD and oral cancer patients were selected for the study.
Materials and Methods: A histopathologically confirmed 100 patients who were suffering from PMD and oral cancers were selected and an equal number 100 healthy controls who were age- and sex-matched at par with the cases were also examined and interviewed. Chi-square (χ2 ) test and adjusted odds ratio (ORs) with 95% confidence interval (CI) were calculated to estimate the suspected risk factors for PMD and oral cancers by using multivariate logistic regression analysis. Significance level was set at P < 0.05.
Results: Statistically significant difference was observed in the age group, socioeconomic status (SES), duration, frequency, exposure time and synergistic effect of tobacco/betel quid chewing, smoking, and alcohol drinking in our study population.
Conclusions: Chewing tobacco/betel quid is a strong risk factor in the development of PMD and oral cancer. Also age, gender, SES, education, and occupation influence the development of PMD and oral cancer.
Keywords: Oral cancer, potentially malignant disorders, tobacco/betel quid
|How to cite this article:|
Kadashetti V, Chaudhary M, Patil S, Gawande M, Shivakumar K M, Patil S, Pramod R C. Analysis of various risk factors affecting potentially malignant disorders and oral cancer patients of Central India. J Can Res Ther 2015;11:280-6
|How to cite this URL:|
Kadashetti V, Chaudhary M, Patil S, Gawande M, Shivakumar K M, Patil S, Pramod R C. Analysis of various risk factors affecting potentially malignant disorders and oral cancer patients of Central India. J Can Res Ther [serial online] 2015 [cited 2020 May 31];11:280-6. Available from: http://www.cancerjournal.net/text.asp?2015/11/2/280/151417
| > Introduction|| |
Chewing tobacco, smoking, and consumption of alcoholic beverages have become common social habits in India. These habits have been positively associated with oral lesions such as oral submucous fibrosis (OSMF), oral leukoplakia, and oral lichen planus which has potential for malignant transformation into oral cancer. ,, Recently the working group of World Health Organization (WHO) termed a new name for all precancerous lesions and conditions as 'potentially malignant disorders' to reflect their widespread anatomical distribution. , The use of tobacco/betel quid can alone lead to death. In 2005, tobacco/betel quid use was responsible for more than 5 million deaths around the world and this number is expected to rise to 10 million deaths annually by 2020. India is the fourth largest consumer of tobacco/betel quid in the world and the third largest producer of tobacco/betel quid after China and Brazil. 
The synergistic effect on the carcinogenic potency of tobacco/betel quid in oral cancer by alcohol consumption is well-documented in the literature. ,, There are about 250 million tobacco/betel quid users in India who account for about 19% of the world's total 1.3 billion tobacco/betel quid users. ,, The prevalence of all types of tobacco/betel quid use among men is about 47% (11-79% in different states) and, among women, smokeless tobacco use varies between 0.2% in Punjab and 61% in Mizoram. Among school-going children in grades 8, 9, and 10; current tobacco/betel quid chewers vary from 2.7% in Himachal Pradesh to 63% in Nagaland. 
In India there are 75,000-80,000 new cases of oral cancer each year  and age-standardized incidence rates per 100,000 populations in India were estimated to be 12.8 in men and 7.5 in women; ,, and these incidence rates are highest when compared to rest of the world. The 5-year survival rate for oral cancer has remained at approximately 50% for the past several decades.  The studies on the relationship between tobacco products and other risk factors like alcohol with synergistic effects in the development of the PMD and oral cancer are lacking in central India or whole India itself. Hence, there is a need for the study in this region to estimate prevalence and to analyze the various specific risk factors in patients suffering from both PMD and oral cancer with different age, gender, and socioeconomic status (SES) group, and investigate synergistic effects (if any) of tobacco/betel quid chewing, smoking, and alcohol consumption.
| > Materials and methods|| |
A case-control study was carried out to assess the prevalence and various risk factors among PMD and oral cancer patients attending hospitals of central India. The data was collected from the patients with clinically diagnosed and histopathologically confirmed PMD and oral cancer patients. Necessary ethical approval was obtained from the higher authorities.
Selection criteria for cases
A total of 100 patients suffering from PMD and oral cancers were selected from outpatient department (OPD) during the study period as and when they presented at Sharad Pawar Dental College and Hospital, Sawangi (Meghe), Wardha. All the selected patients were brought to the Department of Oral Pathology and Microbiology, examined, and interviewed.
The patients who were undergone treatment for the PMD and oral cancers are excluded from the study. A pilot study was conducted to assess the feasibility of the study. After the results of pilot study, the sample size (n) was determined to be 100 subjects suffering from PMD and oral cancer and 100 healthy control subjects. The study was conducted over a period of 2 years from September 2008 to August 2010.
A prestructured questionnaire pro forma was used to record all the relevant information like patient's age, sex, education, occupation, family's monthly income and place of residence, literacy of the study subjects, history, quantity, duration and frequency of smoking, alcohol drinking, chewing habits, and type of areca quid (areca nut, kharra/mawa, pan masala, gutkha) along with or without tobacco and lime. The education of the patient was categorized into illiterate or literate and if literate, the level of education further categorized into primary, middle, and high school (secondary, 12 th standard, and degree). Income was graded 'low', if it was less than Rs. 1,500; 'low to medium' between Rs. 1,500 and 3,000; and 'medium to high' for income more than Rs. 3,000 per month.  The patients' age was grouped into 10-year age intervals up to 70 years to analyze the decade-wise prevalence of PMD and oral cancer. A SES was created based on the Hollingshead two-factor index  by using education and occupation. The SES index was estimated by using the formula:
SES index = (Education × 3) + (Occupation × 5)
The minimum value of the SES index was 8 for a subject who has a manual occupation and is in the education category illiterate. The maximum value of the SES index was 44 for a subject who has a professional/business occupation and professional education. The SES index was categorized into quartiles: 1-14, 15-19, 20-25, and ≥26.
Selection criteria for cases
The controls were defined as subjects who were diagnosed free of potentially malignant disorders (PMD) and oral cancers. An equal number (100) of healthy controls with age- and sex-matched at par with the cases were selected from general population and attendants of the patients who visited the Sharad Pawar Dental College and Hospital, Sawangi, Wardha. The purpose of the study was explained in their local language (Marathi) to all the cases and controls and an informed consent was obtained.
The recorded data from the 200 cases and controls were subjected to statistical analysis. Chi-square (χ2 ) test and adjusted odds ratio (ORs) with 95% confidence interval (CI) were calculated to estimate the suspected risk factors for PMD and oral cancers by using multivariate logistic regression analysis. , The Statistical Package for Social Sciences (SPSS) version 17.0 was used for the statistical analysis and the significance level was set at P < 0.05.
| > Results|| |
Our study results showed that the patients who suffered from PMD was 35.4% of study population in 21-30 years of age, 27.7% in 41-50 years of age as compared to oral cancer; 62.9% were seen in more than 50 years of age and 25.7% of population was in 41-50 years of age groups (P < 0.001, highly significant (HS)). Statistically significant difference has been observed between different age groups among study population [Table 1].
In PMD, 35.4% were middle school educated and 29.2% were primary school educated; whereas in oral cancers, 45.7% were primary school educated, 22.9% were literate, and 17.1% were illiterate. In controls 32% were primary school educated, 23% in middle school educated, and 21% were more than high school educated (P < 0.001, HS). Statistically significant difference has been observed between education level and study population [Table 2].
In PMD, 36.9% of population was in 20-25 SES index quartiles, 20% were seen in both 1-14 and 15-19 of SES index quartiles. Similarly in oral cancer cases, 42.9% of populations were in 1-14 SES index quartiles, 31.4 and 22.9% were 15-19 and 20-25 SES index quartiles category, respectively. In control groups, 28% were in ≥26 and 25 and 24% in 20-25 and 15-19 SES index quartiles, respectively. The results showed statistically significant difference in SES index and study population [Table 3].
|Table 2: Education - wise distribution of cases with potentially malignant disorders, oral cancer, and control group|
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|Table 3: Distribution of socioeconomic status index in cases with potentially malignant disorders, oral cancer, and control group|
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The duration of tobacco/betel quid chewing habits among study population showed that 34% of population chewed tobacco/betel quid for 5-10 years, 29 and 23% chewed for 10-20 and ≥20 years of duration, respectively. Whereas in controls, 43.7% chewed tobacco/betel quid for 3-5 years and 40.6% chewed for 1-3 years of duration (P < 0.001, HS). Statistically significant difference was noted between duration of tobacco/betel quid chewing and in study population [Table 4].
|Table 4: Distribution of duration of tobacco quid/betel quid chewing habits among cases and controls|
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Among cases, 87% population chewed the mixed type of tobacco (chew betel quid, tobacco/gutkha/kharra) and 6% chewed betel quid without tobacco. Statistically highly significant difference was observed between different forms of tobacco chewing among study population [Table 5].
|Table 5: Distribution of different form of chewing tobacco among cases and controls|
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The odds of developing PMD cases (OR = 42.0, 95% CI 7.2-251.6); in oral cancer (OR = 43.0, 95% CI 3.7-218.0) and in multiple cases (OR = 57.0, 95% CI 8.5-143.0); as the frequency of tobacco/betel quid chewing habits increases the risk of developing PMD and oral cancer increases [Table 6].
|Table 6: Distribution of odds ratio for frequency of tobacco/betel quid chewing among study population|
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The occurrence of PMD among subjects with cigarette smoking, tobacco/betel quid chewing, and alcohol drinking was 2.2 times higher than nonchewers, nonsmokers, and nondrinkers. Male subjects whose habits were limited to alcohol drinking and women were not entered to the model on risk analysis for PMD. Similarly tobacco/betel quid chewing and alcohol drinking have 10.4 times and only tobacco quid chewing had 2.5 times higher occurrence of PMD than nonchewers, nonsmokers, and nondrinkers; also higher occurrence of PMD than nonchewers, nonsmokers, and nondrinkers [Table 7].
|Table 7: Synergistic effect of smoking, tobacco/betel quid chewing, and alcohol drinking for potentially malignant disorders by logistic regression analysis risk factor|
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The occurrence of oral cancer patients among subjects with cigarette smoking, tobacco/betel quid chewing, and alcohol drinking was 7.6 times higher than nonchewers, nonsmokers, and nondrinkers. Male subjects whose habits were limited to alcohol drinking and women were not entered to the model on risk analysis for oral cancer patients. Hence, alcohol drinking and female were not considered as independent variables in the model. Similarly, tobacco/betel quid chewing and alcohol drinking had odds of 2.0 times and only tobacco/betel quid chewing had odds of 2.8 times higher occurrence of oral cancer patients than nonchewers, nonsmokers, and nondrinkers [Table 8].
|Table 8: Synergistic effect of smoking, tobacco/betel quid chewing, and alcohol drinking for oral cancer by logistic regression analysis|
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The multiple logistic regression analysis for PMD and oral cancer showed that the most of the factors like age, occupation, education, income, smoking habits, duration of tobacco quid chewing habits, frequency of tobacco chewing habits interacted, and showed strong association in contributing the development of PMD and oral cancer cases [Table 9].
|Table 9: Multivariate analysis of different variables in cases with potentially malignant disorders and oral cancers|
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| > Discussion|| |
Oral cancer remains one of the most life-threatening oral diseases in the world. Oral cancer globally is the sixth most common cancer and is a major problem in regions where tobacco use is prevalent in the form of chewing and smoking. Its distribution and occurrence varies by age, ethnic group, lifestyle, and SES of individuals. It also varied from country to country. ,,
These days the world is heading towards epidemics of various types of noncommunicable diseases, which are also known as modern epidemics. Among these modern epidemics, cancer is the second commonest cause of mortality in developed countries. In developing countries, cancer is the 10 th most common cause of mortality. Oral cancer represents approximately 13% of all cancer, thereby translating into 30,000 new cases every year.  In the South Asian region over one-third of tobacco consumed is smokeless. Traditional forms like betel quid, tobacco with lime, and tobacco tooth powder are commonly used and the use of new products is increasing, not only among men but also among children, teenagers and women. Many cross-sectional, longitudinal, and case-control studies have been conducted in India and other parts of the world assessed the relationship between various risk factors involved in the development of PMD and oral cancer. ,,,,,, It is also observed that still there is a paucity of studies from the central India which has the dubious distribution of being the cancer capital of India.  In the present case-control study, we have analyzed the various risk factors which have played a role in development of PMD and oral cancer.
The age range of occurrence of PMD in our study population was 11 to ≥50 years and 35.4% of PMD cases were seen in 21-30 years of age group. Highest numbers of oral cancer cases were seen in age group of 31 to ≥50 years. Statistically significant difference was observed between different age groups in PMD cases and oral cancer cases (P < 0.001, HS). Several studies , showed that males were more affected as compared with females and this finding was in concordance with our study results (i. e., males were more affected than females). The mean age for initiation of any habit was between 16 and 18 years, a critical period for developing behaviors and responses and a prime time to actively prevent the habits.  The occurrence of PMD cases at an earlier age as compared to oral cancer cases points to the time lag apparently present when PMD may convert into oral cancer. In our study it shows that education level of PMD cases is more when compared to oral cancer cases (P < 0.001, HS). Higher education and higher income was protective against PMD and oral cancer.  Statistically significant difference was observed between SES index and study population (P < 0.014, S). The individuals with low income and less education were more likely to chew tobacco/betel quid, smoke cigarettes, drink alcohol, and eat less fruits and vegetables. ,
A review of cancer incidence and mortality in different socioeconomic levels around the world concluded that most of the studies did not show a clear trend in terms of incidence, but excess mortality was observed for lower SES in various populations. , But in our study, we have found higher prevalence of oral cancer for lower SES. The SES may affect a variety of lifestyle factors that alter the risk of oral cancer as well as PMD, (including tobacco/betel quid chewing, smoking, and alcohol drinking). The psychosocial factors such as lack of social support or perception that health is not within the control of the individual may be intermediate factors in association of SES in PMD and oral cancer cases. In our study; higher SES index, higher education, and high income were associated with a decreased risk of oral PMD and cancer of oral cavity.
Tobacco chewing is a significant finding since it proves, beyond any doubt, that the tobacco chewing habit is essential to trigger changes leading to develop the PMD and oral cancer. Our study results were in agreement with the studies conducted at different parts of world. , Our study results showed an odds of 41 times for developing PMD in tobacco/betel quid chewers as compared to nonchewers which is distinctly higher than those studies conducted by Ariyawardana et al., in Sri Lanka  and Chung et al., in southern Taiwan,  which showed an odds of 16.2 and 8.4 times of developing the disease, respectively. This difference could be due to the differences in habits practiced by different study population group and also the composition, method of chewing which varies from country to country. Similarly for oral cancer cases, 21.7 times of developing oral cancer were observed between tobacco/betel quid chewers as compared to nontobacco chewers. Our study results were consistent with other studies conducted in India. ,
In various parts of India, the relative risk of developing oral cancer ranged from 3.9 to 39.5, this suggests that the daily frequency and duration of tobacco/betel quid chewing are the major predictors of risk. The predominance of occurrence of oral cancer is probably due to the constant contact with the tobacco/betel quid while chewing. It is likely that carcinogens in the tobacco/betel quid act as contact carcinogens.  The carcinogenic process is multiple staged, and the major effect of tobacco/betel quid might be in the relatively early phase or initial stage of carcinogenesis.  In cases, 34% chewed tobacco/betel quid for 5-10 years followed by 29% for 10-20 years and 23% cases for ≥20 years. Similarly, 43.7 and 40.6% of controls chewed tobacco/betel quid for 3-5 and 1-3 years, respectively. In our study, odds of development of PMD cases was 234 times more (OR = 234, 95% CI 13.0-517) and for oral cancer, it was 156 times more for developing the disease (OR = 156, [TAG:2][/TAG:2]
95% CI 353.6). In our study; it was seen that as the duration of tobacco/betel quid chewing habits increases, the risk of developing PMD and oral cancer were also increased. Similar outcome have been observed in other studies conducted at different parts of world. ,,,,,
In our study it was found that, 53% of cases chewed tobacco/betel quid for four to five times, followed by 25% who chewed continuously, 19% chewed two to three times, and 3% chewed occasionally (day). In frequency of tobacco/betel quid chewing habits, the odds of development of PMD cases was 162 times more (OR = 162.0, 95% CI 24.0-218.9), while in oral cancer cases it was 312 times more (OR = 312, 95% CI 18.0-682.6) in development of disease. As the frequency of tobacco/betel quid chewing increased, the likelihood of development of PMD and oral cancer was also increased. These results were in concordance with the results of various studies conducted at across India. ,,,, In our study, the exposure time of tobacco/betel quid chewing habits increased the risk of development of PMD and oral cancer. Also statistically significant difference was observed between exposure time of tobacco/betel quid chewing between cases and controls. The results were in agreement with the studies conducted by Tomar et al., in India. 
The synergistic effect of smoking, tobacco quid chewing, and alcohol drinking habits were analyzed for both PMD and oral cancer cases by using multiple logistic regression analysis. The presence of one risk factor enhanced the effects of the second risk factor and it showed synergism in development of PMD and cancer of oral cavity. Synergistic effect risk factors implies that the ingredients of a joint supplement product are effective due to their ability to work together, in other words, it is the combination of ingredients that give the product its effectiveness, rather than just the presence of each one individually. In our study, an odds of 2.2 times more of developing PMD cases are observed for combination of risk factors, that is, smoking + tobacco quid chewing + alcohol drinking. In oral cancer cases, an odds of 7.6 times for smoking + tobacco quid chewing + alcohol drinking. This shows that there is some synergistic effect of risk factors alone or in combination in developing PMD and oral cancer cases. But interestingly in our study, lesser odds of 0.7 are observed for smoking alone in oral cancer cases, which indicates that only smoking habits cannot cause oral cancer but with combination of other risk factors it can act as a promoter in facilitating the malignant transformation from PMD to oral cancer. These reports were consistent with the other study conducted at Taiwan. 
In conclusion, our case-control study investigated the relationship between chewing tobacco/betel quid, smoking, and alcohol drinking as a risk factor in the development of PMD and oral cancer. Our study results indicated that chewing tobacco/betel quid is a strong risk factor in the development of PMD and oral cancer. Also age, gender, SES, education, and occupation influenced the development of PMD and oral cancer.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]