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 » Introduction
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MINI SYMPOSIUM: GASTROINTESTINAL
Year : 2012  |  Volume : 49  |  Issue : 2  |  Page : 245-250
 

Risk factors and survival analysis of the esophageal cancer in the population of Jammu, India


1 Genome Research Laboratory, School of Biotechnology, University of Jammu, India
2 Department of Gastroenterology, Government Medical College, Jammu, India

Date of Web Publication25-Oct-2012

Correspondence Address:
M K Dhar
Genome Research Laboratory, School of Biotechnology, University of Jammu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.102921

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 » Abstract 

Objective: To identify the risk factors of esophageal cancer and study their effect on the survival rates patients of Jammu region, India. Materials and Methods: Detailed information was collected on socio-demographic, dietary and clinico-pathological parameters for 200 case control pairs. Discrete (categorical) data of 2 independent groups (control and cases) were summarized in frequency (%) and compared by using Chi-square (χ2 ) test. The mean age of two independent groups was compared by independent Student's t-test. To find out potential risk factor (s), the variable (s) found significant in univariate analysis were further subjected to multivariate logistic regression analysis. The association of potential risk factors with patients survival (3-year overall survival) was done by Kaplan-Meier survival curve analysis using Log-rank test. A 2-tailed (a = 2) P < 0.05 was considered statistically significant. Results: Out of the 63 response parameters, seven were found highly significant on multivariate analysis. The mean (± SD) age was 56.74 ± 10.76 years, the proportions of males were higher than females, mostly illiterate and lower income group. Among dietary characteristics, snuff was highest (OR = 3.86, 95% CI = 2.46-6.08) followed by salt tea (OR = 2.53, 95% CI = 1.49-4.29), smoking (OR = 1.97, 95% CI = 1.18-3.30), sundried food (OR = 1.77, 95% CI = 1.10-2.85) and red chilly (OR = 1.76, 95% CI = 1.07-2.89). Probability of survival lowered significantly (P < 0.05 or P < 0.01 or P < 0.001) in those consuming tobacco in the form of snuff (Log-rank c 2 = 24.62, P = 0.000) and smoking (Log-rank c 2 = 5.20, P = 0.023) as compared to those who did not take these. Conclusions: The analysis finally established snuff (smokeless tobacco) as the most powerful risk factor of esophageal cancer in Jammu region, followed by the salt tea, smoking and the sundried food.


Keywords: Esophageal cancer, multivariate, risk factors, survival


How to cite this article:
Sehgal S, Kaul S, Gupta B B, Dhar M K. Risk factors and survival analysis of the esophageal cancer in the population of Jammu, India. Indian J Cancer 2012;49:245-50

How to cite this URL:
Sehgal S, Kaul S, Gupta B B, Dhar M K. Risk factors and survival analysis of the esophageal cancer in the population of Jammu, India. Indian J Cancer [serial online] 2012 [cited 2019 Nov 13];49:245-50. Available from: http://www.indianjcancer.com/text.asp?2012/49/2/245/102921



 » Introduction Top


Considerable amount of research work has been conducted to understand the etiology and molecular biology of carcinoma. [1] Esophageal cancer is the 8 th most frequently occurring cancer worldwide and a common cause of cancer deaths in developing countries. One of the high incidence areas of the "Central Asian esophageal cancer belt" is the Jammu and Kashmir State of India. [2] Although, the incidence rates are largely influenced by the geographical location yet, no report has so far identified a single risk factor, which could explain the high incidence of cancer in this region. In few studies, an attempt has been made to understand its prevalence in the Kashmir region, but Jammu region has remained unexplored. [3],[4] Peculiar dietary habits, demography and geographical location have strongly been implicated in human carcinoma esophagus. [5] The present study involving the detailed risk factor analysis of esophageal cancer from different population groups of Jammu represents the 1 st attempt of its kind. Univariate and multivariate analysis of these parameters was conducted to identify the possible and independent risk factors out of the various response statements.


 » Materials and Methods Top


The sample collection was carried out from the patients attending the Endoscopy Unit of Government Medical College, Jammu between Oct' 2007- July' 2011. The sample size was calculated using EORTC protocol. [6] Cases below the age of 80 years were selected after histological confirmation of the squamous cell carcinomas of the esophagus. Those confirmed for the adenocarcinoma were not included in the study. The control group comprised of the patients admitted to the same hospital for some other illness (ear, eye or skin disorders). One control was matched to each case by age (within 5 years), gender and ethnicity. However, all admission diseases which were known or suspected to have arised from alcohol use, smoking and modified dietary patterns were carefully excluded from the study. Demographical and risk factor data were collected using a short structured questionnaire, including information on age, gender, educational level, socio-economic status, family history of esophageal cancer (first-degree relatives), clinic pathological symptoms and dietary habits. The questionnaire has been designed and tested on the Kashmiri population as reported previously. [7] Since there are major differences in the dietary habits of the inhabitants of Jammu region, the questionnaire was modified to a little extent. The information was gathered from the patient or from the attendant by the researcher or by trained personnels. All participants signed a consent form before starting the interview. Subjects were asked to recall their usual diet over the last year. Frequency (daily, weekly, monthly and annually) and portion size of consumption were asked for each food item. Amounts of dietary nutrients per day were calculated by multiplying the frequency of consumption of each food by the nutrient content of the indicated portion size. To improve accuracy of obtained data, food models and photographs were used and 1 of the attendant was asked to help them to answer the questions. For the clinic-pathological symptoms OES-18 questionnaire of EORTC was used. [8] Similarly, the information was collected for the controls.

Univariate logistic regression analysis was performed to calculate odds ratios (ORs) and to examine the predictive effect of each factor on risk for esophageal cancer; P < 0.05 was considered statistically significant. Discrete (categorical) data of 2 independent groups (control and cases) was summarized in frequency (%) and compared by using Chi-square (c 2 ) test. The mean age of two independent groups was compared by independent Student's t-test. To find out the potential risk factor (s) among the response statements, the variable (s) found significant in univariate analysis were subjected to forward selection by multivariate logistic regression analysis. To study the association of the identified potential risk factors with patient survival (3-year), Kaplan-Meier survival curve analysis (using Log-rank test) was performed. A two-tailed (a = 2) P < 0.05 was considered statistically significant. Point estimates of the cumulative survival were also calculated.


 » Results Top


The demographic characteristics of the 2 groups (controls and cases) are summarized in [Table 1]. The age of two groups ranged from 34-80 years with mean (± SD) 56.74 ± 10.76 years and 56.68 ± 11.17 years, respectively. In both groups, the proportions of males were higher than females, mostly illiterate and lower income group. On comparing, the demographic characteristics of two groups were found to be the same i.e. they did not differed significantly (P > 0.05) [Table 1].
Table 1: Demographic characteristics of control subjects and cases

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However, the life style characteristics; alcohol (c 2 = 9.62, P = 0.002), snuff (c 2 = 42.30, P = 0.000) and smoking (c 2 = 7.72, P = 0.005) differed significantly (P< 0.01) between the 2 groups [Table 2]. Similarly, dietary characteristics; intake of butter (c 2 = 14.45, P = 0.000), sundried food (c 2 = 10.29, P = 0.001) and red chilly (c 2 = 18.78, P = 0.000) differed significantly (P< 0.01 or P < 0.001) between the 2 groups while fruits, egg, rice, kehwa (green tea) and oil did not differ (P > 0.05) much [Table 3]. The wheat intake was the only dietary characteristic found common between the all control subjects and cases. The beverage intake was similar (P> 0.05) between the two groups except the use of baking soda whose intake was significantly higher in the cases (P < 0.001) as compared to the controls (c 2 = 14.44, P = 0.000) [Table 4].
Table 2: Life style characteristics of control subjects and cases

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Table 3: Dietary characteristics of control subjects and cases

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Table 4: Beverage intake of control subjects and cases

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Logistic regression analysis [Table 5] showed that smoking (OR = 1.97, 95% CI, 1.18-3.30), snuff (OR = 3.86, 95% CI, 2.46-6.08), sundried food (OR = 1.77, 95% CI, 1.10-2.85), red chilly (OR = 1.76, 95% CI, 1.07-2.89) and baking soda (OR = 2.53, 95% CI, 1.49-4.29) were significant (P < 0.05 or P < 0.01 or P < 0.001) potential risk factors for esophageal cancer. Among these, snuff was the highest (OR = 3.86, 95% CI = 2.46- 6.08) followed by baking soda (OR = 2.53, 95% CI = 1.49-4.29), smoking (OR = 1.97, 95% CI = 1.18-3.30), sundried food (OR = 1.77, 95% CI = 1.10-2.85) and red chilly (OR = 1.76, 95% CI = 1.07-2.89).
Table 5: Logistic regression analysis of statistically significant factors

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Further, the results of the association of these risk factors (snuff, smoking, sundried food, red chili and baking soda) with patient (cases) 3-year overall survival, done by Kaplan-Meier survival curve analysis, is summarized graphically in [Figure 1]. It clearly shows that the probability of survival lowered significantly (P < 0.05 or P < 0.01 or P < 0.001) in patients who took snuff (Log-rank c 2 = 24.62, P = 0.000), red chilly (Log-rank c 2 = 9.67, P = 0.002) and smoked (Log-rank c 2 = 5.20, P = 0.023), as compared to those who did not. Significant differences in 1-year and 2-year survival were seen between patients diagnosed during the earliest (2007-2008) and those diagnosed during the most recent (2009-2010) time periods. 2-yr survival rose from 43% (95% CI = 42-43) in 2007-08 to 45% (95% CI = 42-46) in 2009-2010 [Table 6].
Table 6: Point estimates for the cumulative survival

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Figure 1: Kaplan-Meier analysis of observed cumulative survival for patients with esophageal cancer by log rank test. Association of these risk factors (snuff, smoking, red chilly, baking soda and sundried food) with the survival of the patients was done to identify the potential risk factors. It is clear from the above graphs that frequency of survival of patients was lowered significantly by snuff, red chilly intake and smoking

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 » Discussion Top


A better understanding of the etiology of esophageal cancer is likely to provide opportunities for primary protection, as it has an extremely poor prognosis and little prospect of improvement in early detection or treatment. Based on our observations, it is apparent that smoking, snuff, sundried food, hot salted tea with baking soda, red chilies are risk factors for the inhabitants of the Jammu region. The results are consistent with the earlier findings where various habits like smoking and consuming alcohol, predispose the subjects to carcinoma. [9]

The risk imposed by some dietary habits is also well supported by the literature wherein it is well known that these foods harbor a good amount of dietary nitrites like N-nitroso-dimethylamine (NDMA), N-nitroso-piperidine (NPIP), N-methylnitrosourea (NMNU), N-nitroso-pyrrolidine (NPYR), polycyclic aromatic hydrocarbons which have been strongly implicated in this type of cancer. [2],[4],[10] Also, general deprivation of dietary nutrients, specifically vitamins A, E, C and of trace elements like zinc and selenium, observed in poor people increases the chances of cancer. [11] Nutrition deficiencies may contribute to high incidence of esophageal cancer by enhancing susceptibility to the effects of other environmental or genetic risk factors, for example, by altering metabolism of carcinogens or by impairing DNA repair. [12],[13] On the contrary, consumption of fruits and vegetables on regular basis shows a protective effect, which may be explained by the presence of vitamins and carotene having antioxidant effects. [14] A significant inverse association between fruit and vegetable intake and the risk of carcinoma esophagus has been reported in several studies. [15] This protective effect has been attributed to the presence of beta-carotene and vitamins C and E in them. [16]

Consumption of sundried spices and vegetables is a commonly used strategy for preservation and storage of foodstuffs by the inhabitants of this region. Due to the nomadic life style, harsh weather and non-availability of fresh vegetables, the tradition of drying and preserving them is followed. Apart from the growth of molds and fungi, presence of trace levels of several volatile and non-volatile N-nitroso compounds like N-nitrosodimethylamine (NDMA), N-nitrosopiperidine (NPIP) and N-nitrosopyrrolidine (NPYR) has been documented in these stored foodstuffs from Kashmir. [4] Intake of sun-dried food was higher among the cases as compared to controls studied for the present work. Most of them belonged to the Kashmiri ethnicity. Salt tea is a common beverage of the region, frequently consumed irrespective of gender or age. Its preparation method includes the brewing green tea leaves with sodium chloride to obtain a reddish brown extract. Further water, salt and milk are added to it. Consumption of bicarbonate-containing hot salted tea, commonly consumed by Kashmiri people, has been identified as dietary high-risk factor associated with the development of esophageal carcinogenesis. [3] It is usually consumed at high temperatures and may cause thermal injury to esophageal mucosa. Its hyperthermic effect may be contributing to the general inflammatory state of the epithelium, leading to the production of oxygen and nitrogen species which enhance mutagenesis. [17] Salted tea prepared by adding sodium bicarbonate has high methylating activity and forms nitro-compounds like mono-nitroso caffeidine and dinitrosocaffeidine on in vitro nitrosation of caffeidine. The structure-activity relationship of these N-nitroso compounds with esophageal cancer makes it a critical risk factor. [18] The present study clearly brings out the role of this tea in as a strong risk factor for esophageal cancer.

Consumption of tobacco was observed to be highest in various forms like cigarettes, hukkas, bidis or snuff. Indians have been known to smoke, chew and snuff tobacco, as early as the 1400s. [19] Snuff intake has been correlated with the esophageal cancer. NNK [4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone], NNN [N'-nitrosonornicotine], and TSNA (tobacco specific nitrosamines) are the leading tobacco carcinogens found in moist snuff. [20] Ample evidences show that chewing habit at a younger age, intake of high doses more frequently during the day and for longer periods of time, predispose a person to a greater risk of cancer. [13] Similar findings have also been reported from different places in India. [21] Majority of the patients studied during the present investigation belong to the low income group like fourth class employees, vendors. Therefore, there is a marked deficiency of vitamins in these people predisposing them to a higher risk of carcinoma. [22]

Strengths of our study include its depth and number of cases, its prospective design and survivorship analysis through which we established potential risk factors of esophageal cancer in our region. However, some weaknesses cannot be overruled. A limitation of the study is the lack of availability of the dietary data of the patients for the previous years, which could have helped in better understanding the role of the identified risk factors. Furthermore, selection bias during the sampling i.e. hospital patient bias (Berkson's Bias) may have occurred in this study. It usually occurs as a result of either some imperfectness in the subject selection for the study or as a result of the factors that influence continued participation of the subjects in a study. People with multiple diseases or conditions become over-represented in the hospital population, and this over-representation affects the distribution of risk factors as well. Berkson bias, also called admission rate bias, was first described in 1946. [23] Further, sampling and data analysis studies have been undertaken by the authors, keeping in mind the approaches to overcome the above limitations.

We conclude that high prevalence of the esophageal cancer in this region can be attributed to the peculiar dietary habits, i.e. consumption of foods harboring high amounts of dietary nitrates by the inhabitants. The frequency of this cancer appears to be lower in Jammu region as compared to Kashmir. Although, the inhabitants of these 2 places share many similarities in the dietary and the life style habits, marked differences in the cooking and preparation methods of the food may account for this. The risk factors predisposing inhabitants of Kashmir to esophageal cancer have been studied previously. [3],[4] Ample literature supports the risk imposed by salt tea, red chilies and other dietary constituents. But, aggravating role of snuff intake and lack of essential nutrients due to low socio-economic status in Jammu region needs to be understood. Survival analysis confirmed the role of these factors in progression of the disease. Timely intervention on the dietary and lifestyle habits in addition to the improvement in the economic status may address the problem to a considerable extent. Further studies are needed to find a correlation between various possible etiological factors and the occurrence of these cancers.


 » Acknowledgments Top


Authors are thankful to Mr. MPS Negi for statistical analysis. Thanks are also due to J and K State Council for Science and Technology, J and K Government for funding the research project.

 
 » References Top

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    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]

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