Tobacco addiction augments obesity and carcinogenesis: Matter of concern for Indian patients.

PURPOSE: Life-style and tobacco addiction is the major risk factors for cancer progression in all over the world. Knowledge gaps between tobacco addiction, obesity and cancer in Indian patients brought an interdisciplinary group of investigators together to discuss the present study. PATIENTS AND METHODS: We calculated the body mass index (BMI) of all the patients (N = 927) who were diagnosed with cancer for its treatment. National Institutes of Health (NIH) criteria were used to categorize the patients. All the patients of this disease could be contacted in person to find out the history of the disease.
RESULTS: The frequency of addiction in urban cancer patient was found to be about 53.3% and in a rural area it was only 33.7%. Tobacco addiction was independently associated with younger age of cancer patient (odds ratio [OR] 2.242; 95% Confidence interval (CI) 1.653-3.042), obese (OR 7.433; 95% CI 3.746-14.750), overweight (OR 4.676; 95% CI 3.381-6.468) and advanced stage of cancer (OR 11.950; 95% CI 5.283-27.030).
CONCLUSION: Tobacco consumption appears to be a major contributor to cancer in younger age with elevated BMI in India. Rapid changes in diet and life-style, increase in tobacco consumption appear to be strongly associated with the carcinoma in this middle-income country.

Addiction of tobacco is the major cause of morbidity and mortality in developed countries and the Indian subcontinent. Tobacco is clearly a human carcinogen and its addiction is associated with the cancer rates in virtually every organ of the body including the lung, oral cavity, esophagus, colon, pancreas, bladder, bone marrow, cervix, kidney,[1] and breast.[2] Understanding the effects of tobacco smoking on the human body is important. The first step is the arrival of carcinogens to critical macromolecules of cell (biologically effective dose). Tobacco smoke contains more than 3,500 chemicals, at least 50 of which are carcinogens.[345] Specific chemicals in tobacco smoke include polycyclic aromatic hydrocarbons (PAHs), N-nitrosamines, aromatic amines, ethylene oxide, 1,3-butadiene, and others. PAHs are derived from tobacco alkaloids and are thought to contribute to cancers of the lung, esophagus, pancreas, and oral cavity. Despite strong epidemiologic evidences linking tobacco and cancer and increased understanding of the molecular biology of tobacco-related cancers, progress in improving smoking cessation and patient management is modest.[6] In areas where tobacco is used in a smokeless form, incidence of the oral cancer is generally high. In the west, especially in the U.S. and Scandinavia, smokeless tobacco is used in the form of the oral snuffs. In India tobacco is smoked in many ways; the most common is bidi, others being chutta, including reverse smoking, hooka, and clay pipe. A voluminous body of research data implicating most of these forms of tobacco use emanates from the Indian subcontinent.[7]

Obesity is increasing at an alarming rate throughout the world. The prevalence of obesity has risen three-fold since 1980's and has now reached an epidemic proportion. Currently, about 400 million adults are estimated to be overweight (a body mass index (BMI) of 25 and over) and some 130 million of these are estimated to be obese (a BMI of 30 and over) in European region.[89] Smoking and obesity are two of the most important global health risk factors. Extensive evidence is available on the broader global determinants of tobacco consumption such as trade liberalization,[10] the global marketing of tobacco,[11] and smuggling.[12]

Tobacco smoking is associated with 12% of the total burden of disease and injury and is the major single contributor to ill health in the Indigenous community, predominantly through ischemic heart disease, Chronic obstructive pulmonary disease (COPD), and lung cancer.[13] Both obesity and use of tobacco are major risk factors for the chronic disease and premature death, both are disproportionately represented among lower socio-economic groups, both carry a social stigma and both are difficult to treat clinically.

A growing body of evidence also indicates that tobacco smoke is an independently associated with the insulin resistance and that the insulin resistant condition may contribute to the accelerated atherosclerosis that leads to excessive cardiovascular disease in the adult smokers.[14] Tobacco smoke is clearly associated with dyslipidemias (increased low density lipoprotein (LDL) and decreased high density lipoprotein (HDL)), (Panagiotakos et al., 2004; Steenland et al., 1998) endothelial dysfunction, and a hypercoagulable state,[15] all of which are also components of the metabolic syndrome. In addition, a dose-response relationship exists with cigarette smoking and the development of type II diabetes in adults.[16] These findings suggest that because both, tobacco and the metabolic syndrome like obesity are individually associated with the insulin resistance. These all entities may be linked through this common pathophysiology and that overweight youth may be especially, susceptible to the impact of tobacco smoke on carcinogenesis, considering that tobacco use and obesity both predispose to the constellation of risk factors seen in the carcinogenesis.

In order to determine the effect of active addiction to tobacco with markedly elevated BMI, age group, and disease advancement among cancer hospitalized patients, a review was made of medical records of individuals in whom an active addiction of tobacco was from 5 or more years in Department of Surgical Oncology, Sir Sundarlal Hospital, Banaras Hindu University, Varanasi (UP), India.

Patients and Methods

This consecutive cluster study included all patients who underwent treatment for invasive cancer at the Surgical Oncology Department, Sir Sundarlal Hospital Banaras Hindu University from January 2006 to April 2009. Exclusion criteria included patients <18 years of age, who received prior treatment in the form of chemotherapy/radiotherapy/surgery and patients who were mentally incapable of giving their own consent.

If the patient met appropriate criteria, we visited the patient before treatment to explain what the study was about and ask for patient participation. After proper consent from the patient, we conducted a 30-min interview with the patient. Data involving presentation, diagnosis, and staging were collected from office charts, hospital charts, and a face-to-face interview with the patient along with a questionnaire that included questions about height and weight, age, health-care and utilization, health habits, nature of food (Fibrous/junk-food/non-vegetarian), addiction, residence, and physical activity level. Diagnosis was defined by the histological presence of the carcinoma tissue biopsy, generally by pre-operative core biopsy.

Out of total N = 927 patients, 269 (29%) of oral cancer, 77 (8.3%) of lung cancer, 268 (28.9%) of gall bladder cancer, 143 (15.4%) of liver cancer and 170 (18.3%) of breast cancer patients.

Estimation of BMI

BMI was measured at the time of hospital admission for treatment and the criteria which were used to categorize patients are given in Table 1.

Table 1

Classification of body mass index in adults

Distribution of patient according to specific addiction

Out of total N = 927 patients, 402 patients are addicted to substances that may be carcinogenic. These patients were further distributed according to their specific substance addiction and interactive substances used are given in Table 2.

Table 2

Distribution of patient according to use of substances addicted

Characterization of patients with socio-economic status and dietary habit

The patients that were included in the study belong to average middle class family of North Indian population. High and low consumption of fat was decided by preliminary evaluation of the diet habit. The process items were distributed with food habit (Fibrous/junk food/non-vegetarian) questionnaire to all members of an outdoor.

Statistical analysis

Demographic presentation and pathological factors were compared among the addicted and non-addicted groups. Two-tailed tests were used at all times, and statistical significance was set a priori at P <.05. Statistical analyses were performed with the SPSS for Windows 16.0. All univariate analyses used Student's t-test or Chi-square tests, as appropriate. Logistic regressions were also performed to evaluate factors associated with the tobacco addiction.

Results

Epidemiologic and demographic presentation of cancer patients

Over the time period of the study, 927 patients underwent treatment for invasive carcinoma out of which 402 patients were addicted with some carcinogenic substances. The mean age of the whole patient was 48.76 ± 8.34 years but for addicted group the mean age was 47.24 ± 8.24 years while it was 49.92 ± 8.24 years for non-addicted patient. The distribution of addicted and non-addicted group is depicted in Figure 1, where we compared these groups with age group, and found that frequency of <45 years of age group is approximately half than, ≥45 years of age group in non-addicted group, but in addicted group frequency is approximately equal.

Figure 1

Patient age distribution with tobacco addiction

Association of demographic presentation with the tobacco carcinogenesis

Association between other demographic and pathological factor with the tobacco addiction are listed in Table 3. The preponderance of the study showed a significant positive association between addicted patient with age group, residence, stage of cancer, and diet nature.

Table 3

Chi-square test derived association between demographic and pathologic factor with tobacco addiction

The frequency of addiction in urban cancer patient is 53.3%, but in rural it is only 33.7%. When we compared these groups with cancer stage, we found a higher frequency of addicted patients were in their third (III) or fourth (IV) stage.

In the context of diet nature, we found 54.7% of addicted patient take high fat content diet and when we compared, this factor showed a significant association with the addiction of tobacco.

Logistic regression was performed to identify demographic and pathologic variables associated with the positive tobacco addiction. Age group < 45 years, higher BMI and advance cancer stage were formed to be independently associated with the tobacco addiction [Table 4].

Table 4

Logistic regression analysis of demographic and pathologic presentation with tobacco addiction

Relationship of demographic and pathological presentation with interactive addiction

Out of total patients (N = 927), 228 (24.6%) patients were found addicted with both tobacco and alcohol. Association of demographic and pathological presentation with interactive addiction is listed in Table 5.

Table 5

Logistic regression analysis of demographic and pathologic presentation with an interactive addiction of alcohol and tobacco

There was a significant association between interactive addiction persisted in multinomial logistic regression analysis, suggesting an independent association between the age group (odds ratio [OR] = 1.945, 95% CI = 1.407-2.688), overweight (OR = 2.090, 95% CI = 1.486-2.939), obese (OR = 2.287, 95% CI = 1.218-4.294), cancer stage III (OR = 3.160, 95% CI = 1.312-7.612), and cancer stage IV (OR = 7.704, 95% CI = 3.113-19.065).

Discussion

From a public health perspective, the effect of tobacco is staggering, perhaps justifying its description as “the dangerous addiction of the developed world.” The detrimental cancer risk and prognosis associated with tobacco add's to the impetus for public health policy, planning, and health education to successfully address the problem of tobacco addiction.

This study showed that the prevalence of tobacco consumption was significantly greater among victims dying due to malignancy and it is also affected by urbanization, sedentary life style, and high content of fat consumption that may lead to obesity [Table 3]. According to Indian Council of Medical Research estimates, the annual estimated mortality due to tobacco-related diseases varies between 630,000 and 1 million. At any point of time, there are about 374,000 cancer patients, 1.89 million patients with coronary artery disease, and 4.8 million patients with the chronic obstructive pulmonary disease, attributable to tobacco usage. The exact prevalence of tobacco consumption, particularly in relation to mortality, is not available from various parts of India.[1718] Various methods of tobacco use such as cigarette, beedi, and hukka (water-pipe) smoking and tobacco chewing are common in different parts of India.[1719202122] The prevalence of smoking varies between 20% and 58% as reported in different studies from India.[1719202122]

Tobacco chewing, beedi, and hukka smoking appears to be more common in rural populations, whereas cigarette smoking and chewing of flavored tobacco are more common in the urban population of India.[2021222324] Among South-East Asian and Pacific Islander populations, chewable concoctions of combined betelnut and tobacco are popular, whereas for groups of Middle Eastern origin, the use of the hookah for smoking tobacco is a popular practice.[2526]

In this study, tobacco uses were ascertained in 43.4% of the cancer cases. Singletarym and Gapstur, explored the association between tobacco use and breast cancer risk was observed that regardless of the type of addiction consumed.[27] The prevalence of smoking varies between 20% and 58% as reported in different studies from India.[17192021] Tobacco chewing, beedi, and hukka smoking appear to be more common in rural populations, whereas cigarette smoking and chewing of flavored tobacco are more common in the urban population of India. Tobacco consumption also damages the taste buds in the oral cavity, which may be a factor in the observed decreases in intake of fruits and vegetables resulting in poor vitamin C and beta-carotine status among tobacco users. These effects are known to predispose to cardiovascular diseases and cancer.[19]

In this study, tobacco addiction was independently associated with a younger age of cancer patient (OR, 2.242; 95% CI, 1.653-3.042), obese (OR, 7.433; 95% CI, 3.746-14.750), overweight (OR, 4.676; 95% CI, 3.381-6.468) and advanced stage of cancer (OR, 11.950; 95% CI, 5.283-27.030) [Table 4]. The interactive addiction (tobacco and alcohol) followed the same pattern like tobacco addiction. Epidemiological studies carried out in India and abroad have shown that increased alcohol consumption is causally associated with cancers at various sites, mainly oral cavity, pharynx, larynx, and esophagus.[28293031] Heavy alcohol drinkers are frequently heavy smokers as well.[3233] The adverse effects of smoking may be because of nicotine, carbon monoxide, and other chemicals, which may enhance carcinogens and free radical generation.[171819,[34],[35363738] Alcohol and tobacco use varied according to gender, age, and ethnicity, with men having higher rates of co-use than women.[39] Younger people tended to have a higher prevalence of alcohol use disorders, nicotine dependence, and co-use.[40] A study of Panagiotakos et al., 2004 and Steenland et al., 1998 suggested that tobacco smoke is clearly associated with dyslipidemias (increased LDL and decreased HDL),[4142] that clearly supports our result. Daniell,[43] demonstrated an independent association between lymph node metastases and obesity that was supported by Schapira et al.,[44] who showed that, in a study of 248 women, obese post-menopausal women were more likely to have axillary node metastases than normal weight patients.

Conversely, no association of tobacco smoking with thyroid cancer was found in two prospective cohort studies of men and women in the San Francisco Bay area,[45] and of Canadian women,[46] but the results were based on relatively small numbers of thyroid cancer patients. Negative associations between alcohol drinking and thyroid cancer have also been reported in some studies,[4748] but the results have been inconsistent.[49]

There has been a marked increase in tobacco production and consumption in the last four decades in India, according to various national and world development reports.[2150]

In developing countries such as India, China, Sri Lanka, and Brazil, massive occupational physical activity in lower social classes is defensive against morbidity and mortality due to circulatory diseases while they continue to have more deaths due to infections and poor nutritional status. Unfortunately, the impact of better education due to lack of health education, possibly, has not yet started in these countries.

Obesity leads to increased levels of fat tissue in the body that can store toxins and can serve as a continuous source of carcinogens. A recent study of Singh et al., explored, breast cancer risk was significantly associated with peri/post-menopausal status, residence, diet nature, and tobacco uses. He also concluded that metastases were identified more commonly with an increasing weight.[51]

Demographic factors, diet, tobacco, and obesity appear to be important causes of death due to cancers in both developed and developing countries. These populations need to learn the methods of prevention for which World Health Organization (WHO) and other International and national agencies are working hard independently. Estimated and projected mortality rates per 100,000 for India's population by the WHO indicate that in the year 2000, all causes of deaths should be 876 in men and 790 in women which should decrease to 846 in men and 745 in women by the year 2015.

Conclusion

In brief, the findings of our study indicated that tobacco consumption has become a public health problem in India irrespective of social classes. The life-style behavior, elevated BMI, younger age group, and advanced cancer stage significantly associated with tobacco addiction. Mass scale and tobacco effect awareness through health promotion programs and medication should be implemented to diminish the risk factors responsible for cancer mortality risk in Northern India.