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Role of Dietary Habits in the Development ofEsophageal Cancer in Assam, the North-Eastern Regionof IndiaRup Kumar Phukan , Chandra Kanta Chetia , Mir Shahadat Ali & Jagadish MahantaPublished online: 18 Nov 2009.

To cite this article: Rup Kumar Phukan , Chandra Kanta Chetia , Mir Shahadat Ali & Jagadish Mahanta (2001) Role of DietaryHabits in the Development of Esophageal Cancer in Assam, the North-Eastern Region of India, Nutrition and Cancer, 39:2,204-209

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Role of Dietary Habits in the Development of EsophagealCancer in Assam, the North-Eastern Region of India

Rup Kumar Phukan, Chandra Kanta Chetia, Mir Shahadat Ali, and Jagadish Mahanta

Abstract: The etiology of esophageal cancer remainslargely unknown. In recent years, the role of dietary habitsin the development of esophageal cancer has received muchattention. Prevalence of esophageal cancer in Assam ishighest among all the states of India. To identify the possiblerisk factors, a hospital-based case-control study was con-ducted with 502 cases and 1,004 controls. “Kalakhar,” aunique and locally made food item, has emerged as a signifi-cant risk factor (odds ratio = 8.0, 95% confidence interval =5.1–11.5, p � 0.001). Consumption of very spicy foods, hotfoods and beverages, a diet containing high amounts ofchili, and leftover food was positively associated with therisk of esophageal cancer. Green leafy vegetables and fruitswere protective for esophageal cancer. The risk factors as-sociated with consumption of locally prepared food items,e.g., kalakhar, and some dietary practices did not decrease,even after adjustments with different confounding factors.However, further studies are required to conclusively impli-cate these factors in causation of esophageal cancer.

Introduction

Esophageal cancer is the sixth most common cancer inthe world (1), and large geographical variations in its inci-dence suggest that environmental exposure is causallyimportant. Records of esophageal cancers from six hospital-based cancer registries in India showed the highest incidencein Assam (2).

Dietary habits as risk factors of esophageal cancer havebeen studied by a number of researchers in relation to thequantity and quality of consumed foodstuffs. Althoughsmoking and drinking are the major risk factors in economi-cally developed countries, high incidence rates of esopha-geal cancer have also been reported in various regions wherealcohol and tobacco are prohibited for religious and otherethnic reasons. Dietary and nutritional conditions in theseareas are regarded as major contributors to the high esopha-geal cancer occurrence (3,4). Locally available and con-

sumed foodstuffs were implicated as risk factors for esopha-geal cancer in some geographical areas of the world (5).

Although in a number of studies (6,7) it has been demon-strated that smoking, chewing of tobacco, and consumptionof alcohol were associated with esophageal cancer, heavytobacco chewers, smokers, and drinkers do not develop thedisease (8). Thus, even with strong carcinogens, there seemedto be secondary factors, either exogenous or endogenous, thatmay have a modifying effect on risks. There was suggestiveevidence from various studies on the role of N-nitroso com-pounds and other dietary factors in the development ofesophageal cancer (9–11). The role of food contaminationby fungus and the presence of toxins, e.g., fumonosins, havealso been documented elsewhere (12,13). Studies on the roleof dietary habits from some geographical areas have shownassociation (14). To determine the role of dietary factors inthe high occurrence of esophageal cancer in Assam, a hospi-tal-based case-control study was undertaken in collaborationwith the Dr. B. Barooah Cancer Institute (BBCI, Guwahati,Assam). This study, among others, was designed to testwhether locally prepared and frequently consumed highlyalkaline food items locally called “kalakhar,” spices, chili,and hot food items enhance the risk of esophageal cancer inAssam in the North-Eastern Region of India.

Kalakhar

The indigenous population of Assam and some neighbor-ing states of the North-Eastern Region of India very fre-quently used a unique food additive commonly known askalakhar. Kalakhar is a highly alkaline (pH 11–12) sub-stance made from the charred false stem or from the skin of aparticular variety of banana. It is preserved for use in theform of coffee decoction or in dark gray powder form and isused as an additive during the preparation of curry or “dal.”Mature banana false stem is peeled, cut, and dried in the sun.After they are completely dry, the false stems are charred ina special furnace or in an open fire. The product is stored inearthen pots for an extended period of time. The water ex-

NUTRITION AND CANCER, 39(2), 204–209Copyright © 2001, Lawrence Erlbaum Associates, Inc.

R. K. Phukan and J. Mahanta are affiliated with the Regional Medical Research Centre, Indian Council of Medical Research, North-Eastern Region,Dibrugarh, Assam, India. C. K. Chetia is affiliated with the Department of Statistics, Dibrugarh University, Dibrugarh, Assam, India. M. S. Ali is affiliated withthe Hospital Tumour Registry, Indian Council of Medical Research, Assam Medical College, Dibrugarh, Assam, India.

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tract is a highly alkaline brown liquid that is filtered throughcloth or a coarse filter.

Kalakhar has been in use in Assam since ancient times,and probably the practice began as a herbal remedy for sorethroat or gastric acidity and gradually became an importantand popular food additive. Kalakhar is a charred product,and, being highly alkaline, it may play a significant role inthe etiology of cancer of the esophagus (15). Therefore, thehypothesis that the use of kalakhar as a food additive couldpossibly explain the increased occurrence of esophagealcancer in Assam should be investigated.

Material and Methods

Study Area

The study was undertaken between July 1997 and June1998 at BBCI. BBCI is one of the regional cancer treatmentand research centers in India and serves the need for cancertreatment in the seven northeastern states of India with apopulation of 31,000,000 (1991 census). Informed writtenconsent of each participant was obtained, and confidentialityof data was ensured.

Study Design

The study was planned and conducted as a case-controlstudy. The retrospective information on exposure factorswas collected simultaneously from all the suspected/provi-sionally diagnosed cases of esophageal cancer (at the time ofregistration) and from the attendants accompanying the can-cer patients. After thorough clinical and laboratory investi-gation of the suspected cancer cases, newly diagnosed andhistopathologically confirmed cases were included in thestudy. Two controls per case, matched for gender and agegroup (World Health Organization age group ± 5 yr) wereselected from the eligible attendants of the cancer patients.

Cases

The case series comprised 502 newly diagnosed consecu-tive esophageal cancer patients registered at BBCI betweenJuly 1997 and June 1998. The cases, confirmed by micros-copy and after verification as having the esophagus as theprimary site of cancer, were included in the cancer series.Extremely advanced cases where the primary site remainedobscured because of dissemination, elderly recurrent cases,and cases who refused to be interviewed were excluded fromthe study.

Controls

Efforts were made to select two controls for each casefrom the attendants accompanying the cancer patients. Al-though the controls were primarily from attendants of

esophageal cancer patients, in a few cases attendants accom-panying other cancer patients were also included as controlswhen eligibility criteria did not match within the selected con-trols. A total of 1,004 controls selected from eligible and co-operative attendants comprised the control series of the study.

Although 585 cases were registered initially during theperiod, only 502 cases were included in the study. Of 83cases who did not participate, 31 dropped out before confir-mation, 20 were cases that were too advanced, 12 were veryold, and 20 were noncooperative and treated outside the hos-pital. Similarly, of 1,120 controls included originally, 116were dropped from the control series.

Data Collection

The majority of the patients came to BBCI with a referralslip from other hospitals/clinics/practitioners with a defini-tive diagnosis or at least with a possible diagnosis of cancer.On their first visit, these patients were registered at the regis-tration counter and were examined on the basis of their refer-ral slip. The cases were then segregated, and the case fileswere prepared and referred to a particular out-patient depart-ment for further investigation. Persons suspected of havingesophageal cancer were directed to the social investigator ofthe project for the collection of required information. Simul-taneously, another social investigator collected informationfrom the attendant controls.

Data Analysis

Epi-info (version 6) was used to process the data, and thefrequency distribution of each of the food items was gener-ated. Analysis was conducted using EGRET (version 0.25.1)and Epixact (version 0.03). Multiple logistic regression (16)was used, since the data were category-matched after selec-tion from the pool of controls, which were matched for gen-der and age of cases, and no pairing identity was retained.Thus the possibility that any member of the case group waspaired with any member of the control group without alter-ation of the basic with stratum structure (gender ± 5-yr agegroup) could not be avoided, thereby making it a sort of“random pairing.”

For each variable in the model (e.g., kalakhar and spices),a parameter estimator (�) and standard error of the estimatewere obtained. Hierarchical models were compared usingthe differences in deviance and in degrees of freedom. Thedifferences in the deviance with its defined degrees of free-dom expressed how significantly a newly fitted variable ex-plained the outcome, i.e., the risk of esophageal cancer. Anodds ratio (OR) representing the relative risks and the 95%confidence interval (CI) for them were calculated from theparameter estimates (�) and their standard errors.

First, factors other than the exposure factor of interestwere fitted to the model. After a search for confounding fac-tors, the exposure factor of interest was added to the model.For comparison, results for exposure factor of interest werealso obtained from models in which confounding variables

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had been omitted. In addition, the results stratified by con-founding variables were used to detect any interaction be-tween the confounder and the exposure under study. Theadjusted estimates were obtained using the possiblecofounders as covariates in the logistic model.

With the objective of staying within the guidelines, aprecoded questionnaire was prepared for data collection.The food frequency questionnaire containing details of di-etary practices prevalent in this region was used. The datawere collected by asking the number of times a food wasconsumed per unit of time (day or week).

Results

The socioeconomic and educational differences of casesand controls are given in Table 1. Esophageal cancer riskwas less among educated and business people and alsoamong the high-income group.

Risk of developing esophageal cancer was increased withincrease in the frequency of intake of kalakhar. Among thosewho consumed the item daily, there was a statistically signif-icant risk (OR = 8.0, 95% CI = 5.1–11.5, p � 0.001). Somefood items, e.g., pickles and papad, if eaten daily at allmeals, were also associated with substantial risk (for pickles,OR = 8.2, 95% CI = 3.9–11.3, p � 0.001; for papad, OR =6.2, 95% CI = 3.8–9.6, p � 0.001; Table 2). Oil, cumin seeds,“jani,” turmeric powder, coriander powder, black cuminseeds, citric acid, acetic acid, salt, and chili powder are someof the ingredients used to prepare pickles; pulses, edible oil,

salt, suji, black pepper, and “hing” are among the ingredientsin papad. Almost everyone uses spices in various forms, themost common spice ingredient being chilies (red and green),cumin seeds, coriander, fenugreek, and black pepper. Thepreparation is mainly in the form of powders and pastes. Anattempt was made to collect information on all types ofspices used in the diet. The respondents knew what spicesthey used but found it difficult to quantify the amount. Be-cause almost everyone used spices, the data could be catego-rized trichotomously, i.e., consumed very spicy food,consumed moderately spicy food, and did not use spices infood. Chili, in the context of the present study, is whole chili(green or red). Preserved food is food kept overnight (soakedin water or dry) and consumed on the next day; it does notinclude refrigerated food.

When the relative risk due to spicy food was estimated,subjects who consumed no spicy food and those who con-sumed highly spicy food were compared with those whoconsumed moderately spicy food in their daily diet. Con-suming very spicy food results in a significant risk (OR =5.1, 95% CI = 2.8–8.5, p � 0.001). On the other hand, nonus-ers of spicy food seem to be significantly protected (p �

0.05) against development of esophageal cancer. Chili(green or red) is considered one of the components of spicesadded during the preparation of curry, but very often wholechili is also taken with a meal. Information on this compo-nent of spice for estimating its relative risk shows that thosewho use a large amount of chili tend to have a higher risk(OR = 6.9, 95% CI = 3.5–10.8, p � 0.001), whereas thosewho do not use chili tend to be protected from the disease.Although the majority of the study population preferredmoderately spicy food items, the risk estimate for those whopreferred spicy food items was high (OR = 6.5, 95% CI =1.8–9.8, p � 0.001). The leftover food items were more com-monly consumed among cases than controls and showedsome amount of risk.

The role of certain dietary factors after controlling for edu-cation, income, the effect of chewing betel nut and tobacco,and smoking and alcohol drinking habits is shown in Table 2.A multivariate model of risk was constructed, including theeffects of dietary variables on esophageal cancer, after adjust-ment for other exposure variables, education, and income.

Kalakhar, which emerged as a potent risk factor foresophageal cancer, has been further tested after adjustmentfor education, income, chewing betel nut and tobacco, andsmoking and drinking habits. Some reduction of risk wasseen among the persons who consume kalakhar daily, butthe risk remains very high even after reduction. The risk in-creased with consumption of pickles after adjustment forother variables, whereas the risk due to papad was reduced.The risk due to the consumption of very spicy food was re-duced by ~50%. As expected, like spicy food, the risk due toa diet with a high chili content was reduced by 50% after ad-justment for other habits. Ingestion of food at very high tem-peratures emerged as a very significant risk factor (OR =6.5) that seemed to persist, although at reduced magnitude,even after adjustment for the other variables (OR = 2.8).

206 Nutrition and Cancer 2001

Table 1. Social Characteristics and Age Distribution ofCases and Controlsa

Social CharacteristicsCases/

Controls OR 95% CI

EducationIlliterate 108/52 1.0Up to primary level 278/397 0.3 0.18–0.5Up to secondary level and more 116/555 0.1 0.04–0.4

OccupationOther 44/23 1.0Cultivator 178/198 0.5 0.3–0.8Service 106/285 0.2 0.08–0.6Business 37/246 0.08 0.04–0.7Housewife 138/252 0.3 0.05–0.9

Income group, rupees/mo�500 8/2 1.0

501–2,000 166/80 0.5 0.2–0.92,001–5,000 289/653 0.1 0.07–0.6

�5,000 39/269 0.04 0.01–0.3

Age Distribution of Cases andControls Cases Controls

�35 yr 8 1635–44 yr 46 9245–54 yr 167 33455–64 yr 233 476

�64 yr 48 86Mean ± SD 55.0 ± 8.1 54.5 ± 7.8

a: Abbreviations are as follows: OR, odds ratio; CI, confidence interval.

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Table 3 shows the ORs and 95% CIs for some of the fooditems that could be evaluated from the study populations.Green vegetables have emerged as a protective factor, andthe people who ingest them daily have a fourfold reductionof risk compared with those who never consume these items.Even the occasional and frequent users also are protected tosome degree. On the other hand, fried vegetables have ap-peared as a risk factor.

Fruits are mostly seasonal and relatively costly in this re-gion, and few people eat fruits daily. Moreover, except forbanana and papaya, fresh fruits are seasonal. So, when theitems are analyzed, a variety of fruits are not considered andalso categorized into groups as never and occasional. Theoccasional consumer of fruits has protection against esopha-geal cancer risk relative to nonusers.

Consumption of animal proteins, e.g., meat and fish, havealso emerged as a protective factor after adjustment for othervariables, but it is difficult to interpret the role of eggs be-cause of different procedures adopted by people to preparean egg dish.

Discussion

The role of diet in the causation of esophageal cancer iscomplex, partly because diet and dietary habits encompass awide variety of foods and because the methods by whichthese habits can be measured are cumbersome as well as dif-

ficult to apply to a large number of individuals. Moreover,the dietary information is limited to subjective variations ofrecall memory of the respondents. In analyzing the predic-tive value of many commonly used food items, it has beenfound that cases and controls are similar in their frequencyof consumption of many food items, such as cereals, andpulses. Because of similarities in their distributions amongcases and controls, the relative risk estimates of these itemscould not be evaluated. However, there are some variationsin consumption of certain food items, which appeared as riskfactors or protective.

Kalakhar, a unique and locally made food additive that isused by the indigenous population of this region, hasemerged as a very significant risk factor. A rigorous investi-gation and experimental evaluation has to be undertaken bytaking into account the confounding effects of other relevantrisk components, such as chewing tobacco, smoking, alco-hol use, and socioeconomic status, to assess the proportionof cases in a given area that might be due to the intake ofkalakhar. This study has been able to provide some clues forfurther investigation into the role of diet and food additivesprevalent in this region in the causation of esophageal can-cer. Perhaps the high alkaline nature of kalakhar might haveplayed a role in inflicting injury and subsequent changes inthe esophageal epithelium.

The present study revealed a very strong association be-tween consumption of pickles and esophageal cancer risk.

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Table 2. ORs for Esophageal Cancer According to Dietary Habits

Dietary Habits Cases/Controls OR 95% CI P Value Adjusted ORa 95% CI P Value

KalakharNever 109/354 1.0 1.0Occasionally 298/589 1.6 0.4–3.4 �0.05 2.1 0.8–4.5 �0.051–4/wk 63/48 4.3 2.4–6.1 �0.001 4.8 2.1–8.3 �0.001Daily 32/13 8.0 5.1–11.5 �0.001 6.8 1.8–9.5 �0.001

PicklesNever 86/327 1.0 1.0Occasionally 345/644 2.0 0.8–4.5 �0.05 2.3 1.1–6.3 �0.05All meals 71/33 8.2 3.9–11.3 �0.001 10.4 4.6–16.9 �0.001

PapadNever 82/340 1.0 1.0Occasionally 363/626 2.4 1.2–4.5 �0.05 1.8 0.8–4.5 �0.05All meals 57/38 6.2 3.8–9.6 �0.001 3.4 1.3–10.6 �0.001

SpicesModerate user 210/509 1.0 1.0Non-user 77/392 0.5 0.04–4.8 �0.05 0.3 0.02–3.8 �0.05Very spicy 215/103 5.1 2.8–8.5 �0.001 2.3 0.6–4.9 �0.01

ChiliModerate user 261/567 1.0 1.0Non-user 62/386 0.3 0.06–3.7 �0.05 0.1 0.05–5.8 �0.05Very chili 179/56 6.9 3.5–10.8 �0.001 3.6 1.8–8.6 �0.01

Food temperatureModerate 436/945 1.0 1.0Cold 30/47 1.4 0.6–4.5 �0.05 1.2 0.04–4.1 �0.05Hot 36/12 6.5 1.8–9.8 �0.001 2.8 0.6–7.5 �0.05

Leftover foodNo 178/630 1.0 1.0Yes 324/374 3.1 0.3–5.2 �0.01 2.6 0.7–7.1 �0.05

a: Variables were adjusted for education, income, chewing betel nut and tobacco, smoking, and alcohol use.

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Recall bias was unlikely to have generated the differencesbetween cases and controls, since the association is notwidely known. There was a clear dose-response relation, andthe effect persisted after adjustment for other possible riskfactors, in contrast to the effects of other dietary variables.Associations between consumption of pickled vegetables,which contain a high concentration of N-nitroso compounds,with esophageal cancer have been documented (17,18). Per-haps the findings of the present study can also be correlatedwith the N-nitroso compound content of food. Previous re-ports that hot food and red chili are risk factors for esopha-geal cancer (14,19) are consistent with the present study.

The protective effects of fruits and vegetables were ap-parent in 10 of the 11 case-control studies (20,21). We alsofound a protective effect of consumption of fruit and greenleafy vegetables. However, the modifying effects of vegeta-bles, fruits, and animal proteins on kalakhar, spicy food,chili, and hot food and beverages need to be examined ingreater detail before any conclusions can be made. Con-sumption of significantly less milk and fewer green and yel-low vegetables has also been implicated in esophagealcancer (22): esophageal cancer cases consumed significantlyfewer green vegetables, fruits, and animal proteins. Owingto the problem of recall and obtaining reliable data on thequantity of dietary items in meaningful measurable quanti-ties, no further analysis could be attempted in this study. Afairly increased risk for low consumption of meat, fish, dairyproducts, eggs, fruits, and vegetables has been reported in a

study from South Africa (23,24). Findings similar to those ofthe present study revealed the negative association of esoph-ageal cancer and the consumption of leafy vegetables, fruits,and animal proteins. The importance of vitamin C was em-phasized in the protective effects of fruits and raw vegeta-bles. It is likely that vitamin C, by blocking the formation ofnitroso compounds, plays a more important role than vita-min A in protecting against esophageal cancer (25).

The consumption of very hot food items as well as hotbeverages has long been considered a potential risk factor.The hot temperature of food items and beverages may causethermal injury to the esophageal mucosa, and dietary defi-ciencies may weaken the esophageal tissue because of theconstant irritation, which may act as a predisposing factorfor esophageal cancer. This might support the findings of thepresent study, where consumption of high-temperature fooditems and hot beverages emerged as risk factors. The inges-tion of exceptionally hot drinks, e.g., mate in South Amer-ica, has been considered a potential risk factor (26). Besidesnutritional aspects of the diet, there are other constituentsthat are very common in the Indian population. A high fre-quency of esophageal cancer has been reported from Kash-mir (India), which has unique dietary habits. The dietaryhabits include consumption of dried and smoked fish anddried and pickled vegetables and excessive use of chilies andspices. Smoke-dried meat consumption by some people ofthe North-Eastern Region of India has been found to be arisk factor for nasopharyngeal cancer (27). These foodstuffs

208 Nutrition and Cancer 2001

Table 3. ORs for Esophageal Cancer According to Consumption of Vegetables, Fruits, and Animal Proteins

Dietary Habits Cases/Controls OR 95% CI P Value Adjusted OR 95% CI P Value

Green leafy vegetablesNever 179/284 1.0 1.0Occasionally 123/206 0.95 0.7–3.6 �0.01 0.73 0.06–3.1 �0.011–4/wk 145/334 0.69 0.4–3.2 �0.01 0.52 0.03–3.5 �0.01Daily 55/180 0.48 0.1–2.8 �0.01 0.26 0.01–2.9 �0.01

Fried vegetablesNever 335/632 1.0 1.0Occasionally 127/312 0.77 0.03–3.6 �0.05 0.62 0.04–3.6 �0.051–4/wk 22/38 1.09 0.02–5.3 �0.05 0.85 0.05–6.5 �0.05Daily 18/22 1.54 0.09–7.2 �0.05 1.15 0.08–9.3 �0.05

FruitsNever 397/680 1.0 1.0Occasionally 105/324 0.5 0.02–6.7 �0.01 0.3 0.08–4.2 �0.01

EggNever 80/209 1.0 1.0Occasionally 225/463 1.2 0.08–4.6 �0.05 0.7 0.05–5.8 �0.051–4/wk 108/238 1.1 0.04–3.8 �0.05 0.4 0.03–4.1 �0.05Daily 89/94 2.4 0.5–6.9 �0.05 1.2 0.08–6.3 �0.05

MeatNever 195/400 1.0 1.0Occasionally 235/443 1.08 0.06–5.8 �0.05 0.95 0.04–3.6 �0.051–4/wk 39/87 0.92 0.05–4.2 �0.05 0.83 0.03–5.1 �0.05Daily 33/74 0.91 0.04–3.7 �0.05 0.72 0.01–4.8 �0.05

FishNever 175/383 1.0 1.0Occasionally 245/453 1.18 0.7–4.5 �0.05 1.07 0.06–4.2 �0.051–4/wk 45/90 1.09 0.5–4.3 �0.05 0.85 0.04–4.1 �0.05Daily 37/78 1.03 0.1–3.6 �0.05 0.82 0.03–3.9 �0.05

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develop nitrosamine because of long preservation and stor-age (28), and thereby the risk for mutagenicity and carcino-genicity is increased.

Spices are a very common component of the diet in India.A close association between the high intake of chilies inManipur, a neighboring state of Assam in the North-EasternRegion of India, and risk of esophageal cancer has been de-scribed (29); the same view can be put forward in the presentinvestigation also. Our finding that excessive use of spicyfoods among our study population might have contributed asa positive risk factor for esophageal cancer is supported instudies elsewhere (25).

The effects of high temperature of consumed food, verystrong chilies, spices, and consumption of leftover food wereevident in this study. Kalakhar, which is consumed in Assamonly, emerged as a distinctive risk factor for esophageal can-cer. To support these findings, an in-depth study with labo-ratory experiment is essential. The risk associated withconsumption of kalakhar in the diet has been found to have avery strong association, even after adjustment with knownconfounding factors. Hence, this appears to be a potent, un-described risk factor of esophageal cancer.

Acknowledgments and Notes

We thank Dr. G. Ahmed (BBCI) for permitting us to do our researchwork in his institute and Dr. A. Nandakumar [National Cancer RegistryProgram (NCRP), Indian Council of Medical Research (ICMR), KidwaiMemorial Institute of Oncology, Bangalore, India] for analyzing ourwork. We acknowledge the technical help provided by Mr. Muralidhar(NCRP, ICMR, Kidwai Memorial Institute of Oncology). Address corre-spondence to Dr. J. Mahanta, Director, Regional Medical Research Cen-tre, North-Eastern Region (ICMR), PB 105, Dibrugarh 786 001, Assam,India.

Submitted 27 June 2000; accepted in final form 7 March 2001.

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