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 Table of Contents  
Year : 2020  |  Volume : 5  |  Issue : 3  |  Page : 149-154

Study of modifiable risk factors for instituting evidence-based preventive strategy for carcinoma esophagus in Punjab: A study protocol

1 Department of Community Medicine and School of Public Health, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab, India
2 Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab, India
3 Department of Paediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab, India
4 Department of Cytology and Gynaecological Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab, India
5 Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab, India
6 Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab, India
7 School of Public Health and Zoonoses. Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, India
8 Centre for Cancer Epidemiology, Tata Memorial Centre, Mumbai, Maharashtra, India

Date of Submission17-Aug-2019
Date of Decision04-Sep-2019
Date of Acceptance20-Jul-2020
Date of Web Publication30-Sep-2020

Correspondence Address:
Dr. Harmanjeet Kaur
Department of Community Medicine and School of Public Health, Post Graduate Institute of Medical Education and Research, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jncd.jncd_33_19

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Background: In Punjab, esophageal carcinoma has been reported as leading cancer in rural population. Reason for this high incidence of esophageal carcinoma in this region is unknown. The life style of people in Punjab is different from those of other areas in India. Therefore, the risk factors contributing to esophageal carcinoma in Punjab may also be different than the other parts of India. There are no previous studies on risk factors for high incidence of esophageal carcinoma in this region. Use of pesticides is much higher in Punjab state. Also there is no evidence available for association of use of pesticides/fumigants in occurrence of esophageal carcinoma. Hence this study is planned to identify the risk factors, especially the role of chemical toxicity (Pesticides/fumigants/heavy metals) associated with development of esophageal carcinoma among inhibitants of Punjab.
Methods: A case-control design will be used to identify potential risk factors associated with development of carcinoma esophagus in Punjab. Cases will be recruited from PGIMER, Chandigarh, Population based cancer registry Mansa, Sangrur, SAS Nagar and Punjab Cancer control cell. For each esophageal cancer case 2 controls will be selected after matching for gender, age and area of residence. A pre designed questionnaire, including demographic characteristics, family cancer history, personal medical history, height, weight, life-style (habits such as smoking, tobacco chewing, alcohol drinking, etc.), dietary habits, fumigants and pesticide usage and practices etc, will be used. Urine samples will be taken for the analysis of pesticide metabolites. Heavy metals analysis will be done in water samples. Oral health will be examined for mucosal changes as well as for oral hygiene.
Discussion: This study will results in identification of risk factors for high occurrence of esophagus carcinoma in Punjab, so that measures for early detection, prevention and control of esophagus carcinoma could be initiated.

Keywords: Cancer, esophagus, heavy metals, oral health, pesticides, risk factors

How to cite this article:
Kaur H, Thakur J S, Dutta U, Attri S, Gupta N, Singh MP, Vaiphei K, S Gill J P, Dikshit R. Study of modifiable risk factors for instituting evidence-based preventive strategy for carcinoma esophagus in Punjab: A study protocol. Int J Non-Commun Dis 2020;5:149-54

How to cite this URL:
Kaur H, Thakur J S, Dutta U, Attri S, Gupta N, Singh MP, Vaiphei K, S Gill J P, Dikshit R. Study of modifiable risk factors for instituting evidence-based preventive strategy for carcinoma esophagus in Punjab: A study protocol. Int J Non-Commun Dis [serial online] 2020 [cited 2021 Feb 25];5:149-54. Available from: https://www.ijncd.org/text.asp?2020/5/3/149/296794

  Introduction Top

Esophageal carcinoma ranks 7th in terms of incidence and the 6th leading cause of cancer-related deaths. About 572,034 new cases and 508,585 deaths were estimated in 2018.[1] In India, the highest incidence has been reported in East Khasi Hills district of Meghalaya (males 71.2 and females 33, age-adjusted rates per 100,000), followed by other areas of Meghalaya state and Aizawl district of Mizoram.[2] Among the two most common histologic subtypes (squamous cell carcinoma [SCC] and adenocarcinoma), SCC is more common in lower income countries.[3]

Much work has been carried out on the role of various environmental factors, dietary factors, cultural factors, gene mutations, and polymorphisms worldwide.[4] Heavy alcohol consumption along with smoking is reported as a strong risk factor for SCC of the esophagus.[5] Among the risk factors in India, betel quid chewing carries a relatively high risk.[6],[7] Although some studies have been conducted in various parts of India, major risk factors for SCC are yet to be elucidated.[8],[9],[10]

In Punjab which is known as “Granary of India,” esophageal carcinoma has been reported as leading cancer in the rural population.[11] The reason for the high burden of esophageal carcinoma in this region is unknown. The lifestyle of people in Punjab is different from those of other areas of India. Therefore, the risk factors contributing to esophageal carcinoma may also be different between Punjab and other areas of India. As Punjab is a farming state, the use of pesticides is much higher.[12],[13] Further use of fumigants in grain storage is also prevalent in India including Punjab.[14],[15] Furthermore, there is no evidence available for the association of the use of pesticides/fumigants in the occurrence of esophageal carcinoma. Heavy metal toxicity has also been reported in Punjab, which is also a known carcinogen.

Since the prognosis of carcinoma is extremely poor and as there seems to be little prospect for early detection or treatment, a better understanding of the etiology/risk factors may suggest an opportunity for its primary prevention. Hence, we have planned a case–control study to identify the risk factors that may have a role in the development of this cancer along with the role of chemical toxicity (pesticides/fumigants/heavy metals) in the occurrence of esophageal carcinoma in this region.

Aim and research questions

The aim of the study is to evaluate the risk factors and devise preventive strategy for carcinoma esophagus in Punjab.

The current study aims to address the following research questions:

  1. What are the reasons for high disease burden of carcinoma esophagus in Punjab?
  2. Is the chemical toxicity has association with the occurrence of carcinoma esophagus in Punjab?
  3. What is the role of oral cavity as predictor for presence of carcinoma esophagus?


Primary objectives

  • To assess the prevalence of risk factors among patients with carcinoma esophagus in Punjab
  • To assess the association of exposure to heavy metals and pesticides/fumigants as a risk factor for the development of carcinoma esophagus in Punjab.

Secondary objectives

  • To study the role of the oral cavity as a predictor for the presence of carcinoma esophagus
  • To develop evidence-based public health interventions to reduce carcinoma esophagus in Punjab.

  Materials and Methods Top

A case–control study will be conducted to identify potential risk factors associated with the development of carcinoma esophagus in Punjab. People who have been living in Punjab for atleast the last 5 years will be selected as participants in this study. Criteria for selection of cases and controls are given below:


Patients diagnosed with esophageal carcinoma in the period between 2015 and 2019 will be recruited for the study. The source of cases will be the Post Graduate Institute of Medical Education and Research Chandigarh, Population-Based Cancer Registry Mansa, Sangrur, SAS Nagar, and Punjab Cancer Control Cell. Patients of age >30 years with a histologically confirmed primary invasive SCC of the esophagus will be included in the study as cases. Patients having a family history of esophageal carcinoma or history of concurrent carcinoma in other organs will be excluded from the study.


For each esophageal carcinoma case, two controls will be selected. Individual matching of cases and controls will be done for gender, age (±5 years), and area of residence. Community-based controls will be selected from the same population to which the case belongs. Hospital-based controls will be selected from the patients reporting to the OPD of various departments of PGIMER, Chandigarh. Patients with diagnosis of any cancer, patients referred for high risk screening for oesophageal carcinoma (e.g. family history), patients with cirrhosis/chronic liver diseases, patients having any oesophageal/gastric structural abnormalities on UGIE such as polyps, ulcers and strictures will be excluded.

Patients having a history of malignancy or a family history of upper gastrointestinal malignancy will be excluded from the study.

Sample size

  • Assumptions: proportion of exposed controls = 8.35%
  • Two-sided confidence level (1-alpha) =95%
  • Power (% chance of detecting) =90, controls/case ratio = 2
  • Odd's ratio = 2 cases = 302 controls = 604
  • Adjustment for confounding factors (15%) and nonresponse (10%) =25% =227
  • Total number of participants = 1133 (cases 378 and 756 controls).

Data collection

A predesigned questionnaire will be used to obtain the study information.

While developing the questionnaires, the focus will be purported risk factors for esophageal carcinoma where there is either clear or mixed evidence of an association with esophageal carcinoma in the literature. The questionnaires will be developed, based on previous questionnaires from other esophageal carcinoma case–control studies and input from experts.

The questionnaire will include information on sociodemographic characteristics including age, ethnicity, education, residence, and occupation. Questions on lifestyle factors will include alcohol consumption, smoked and smokeless tobacco use, drug abuse, hot beverage and hot food consumption, and oral hygiene habits.

For tobacco use, each participant will be asked whether he had ever smoked at least one cigarette per day continuously for six months or longer. If he answer yes, he will be further asked about the age at which he/she started to smoking cigarettes regularly, the average number of cigarettes smoked per day, and the number of years he/she has smoked. Information on the use of bidis, piped smoking and smokeless tobacco will also be collected. If the subject had quit tobacco use (smoked as well as smokeless) at the enrollment, the age at which he stopped the use will be recorded.

For alcohol consumption, each participant will be asked whether he/she had ever drunk alcoholic beverages at least once a week continuously for six months or longer. If the answers yes, he/she will be asked to provide the age at which he started to drink regularly, type and usual amount of beverage consumed. If the subject had quit the drinking habit at the time of interview, the age at which he/she stopped drinking will be recorded.

Past dietary history will be taken by the food frequency method, i.e., frequency of consumption per week of the common food items in the diet, such as milk and dairy products, meat, fish, eggs, green leafy vegetables, fruits, and other vegetables. We will also calculate the body mass index as per the revised consensus guidelines for India. Personal medical history apart from cancer will also be taken from the participants.

Environmental factors of interest will be pesticide exposure (occupational and nonoccupational), grains storage and usage practices, availability and use of fumigants/pesticides during storage of grains, predominant drinking water supply, and cooking in the home (fuel type and ventilation in cooking area).

Clinical and laboratory procedures

Oral cavity examination

Measures of oral health will be performed using the dental hand instruments. All instruments will be sterilized with a portable steam autoclave. All participants will be required to rinse with water before the oral health examination and remaining food debris covering tooth surfaces will be removed with 2 × 2 sponges and the explorer. Examinations will be performed with artificial light.

The tooth count assessment involves examining the maxillary and mandibular arches to identify the presence or absence of permanent teeth and retained dental roots. Missing teeth will be subclassified into (1) extraction due to caries or periodontal disease or (2) extraction due to other reasons such as trauma. DMFT (decayed, missing, and filled teeth) scores will be calculated. Oral cavity will also be assessed for mucosal conditions including gingivitis, periodontitis, leukoplakia, lichen planus and oral submucous fibrosis(OSMF).

Collection of oral mucosal samples for cytological changes

The participants will undergo oral brush cytology using a commercially available medium nylon toothbrush (sterilized in 0.2% of chlorhexidine gluconate mouthwash for 24 h). Using moderate pressure, the brush will be repeatedly brushed in one direction over the entire area of interest many times until pinpoint bleeding is observed, signaling entry into the lamina propria and thus obtaining epithelial cells through the full thickness of the epithelium. The material from the brush will be transferred into SurePath ® liquid-based CytoRich Red preservative solution for further processing with the help of SurePath ® automated LBC machine. All the samples will be examined manually by an experienced cytopathologist in the Department of Cytology and Gynaecological, PGIMER, Chandigarh. Cytological diagnoses will be performed based on the Bethesda System.

Collection and analysis of urine samples for pesticide metabolites

The study participants will be asked to provide their urine sample directly into a 50 mL sterile container made from polyethylene. Urine samples will be aliquoted into four 5 mL vials and stored at −80°C for future analysis of metabolites of pesticides at the Department of Paediatric Biochemistry, Advanced Paediatrics Centre, PGIMER, Chandigarh.

These urine samples will be analyzed for pesticide metabolites with standard methods (GC-MAS) on a sample basis depending upon the availability of resources and funds for the same.

Collection and analysis of drinking water samples for heavy metal analysis

Drinking water samples obtained from the household of the participants and will be kept separate in suitable plastic containers and labeled appropriately. Five (5.0) mL of each water sample will be volumetrically transferred into a 50 mL digestion vial using a calibrated pipette. All samples will be analyzed for heavy metals using ICP-MS instrument with the standard parameters.

On the basis of data on risk factors, various interventions influencing the multiple risk determinants to prevent or reduce the risk of carcinoma esophagus will be recommended to the government. State level workshop with various stakeholders including the health department will be conducted for dissemination of study findings.

Data analysis plan

Statistical analysis will be performed using SPSS version 23.0 (IBM, New York, NY, USA). Univariate analysis for categorical data will be done by Chi-square test and Fisher's exact test wherever possible. The odds ratio associated with a given risk factor or level of a categorical variable will be estimated, along with its 95% confidence interval. Statistical significance will be set at 0.05. All reported P values will be from two-sided tests. Confounding will be dealt at the analysis stage using statistical techniques including adjustment and multivariate techniques.


The National Programme For Prevention and Control of Cancer, Diabetes, Cardiovascular Disease, and Stroke (NPCDCS), Department of Health and Family Welfare Punjab, will be partners from the very beginning for translating the work.

Ethical approval

Ethical permission to carry out the study has been obtained from the Institution Research and Ethical Committee, PGIMER, Chandigarh.

Study timelines

We aim to have data collection, analysis, and dissemination completed by the end of 2020.

  Discussion Top

The etiology of esophageal carcinoma is diverse and complex. The uneven geographical distribution of esophageal carcinoma is probably due to different dietary, environmental, and cultural risk factors.

The use of tobacco products, including cigarettes, cigars, pipes, and chewing tobacco, is a major risk factor for esophageal cancer. Studies have shown that risk of Esophageal Squamous Cell Carcinoma is increased by approximately 1.5–7-fold in smokers.[16],[17],[18],[19],[20],[21] Both duration and daily amount of smoking are major determinants of esophageal carcinoma risk associated with tobaccouse.[22]

Salaspuro et al. have reported that combined habit of alcohol drinking with tobacco smoking and/or chewing shows a synergistic effect in causing esophageal carcinoma.[22]

A study done by Prasad et al. has reported that the deficiencies of certain vitamins and micronutrients impair the structure of esophageal epithelium which may increase the degree of contact with or susceptibility of the esophageal wall to penetration by environmental carcinogens.[11]

Guha et al. (2007) have reported that periodontal disease as indicated by the poor condition of the mouth and missing teeth may be independent causes of cancers of the head, neck, and esophagus.[10]

For the role of pesticide in the etiology of esophageal carcinoma, Meyer et al. demonstrated the death risk related to esophageal cancer among Brazilian agricultural workers who were exposed to a high level of pesticides.[23] Similarly, Chrisman et al. also reported a significant relation between pesticides and esophageal cancer.[24] However, contrary results were reported by Jansson et al. andYıldırım et al.[25],[26]

In Punjab, as per the study done by Thakur et al. (2008), pesticides and heavy metals have entered into the food chain and thereby into the human body. The levels of As, Se, and Hg in groundwater of Talwandi Sabo area of Punjab were more than the permissible level.[13]

Another study also reported manifestations of genotoxic effect possibly due to heavy metals and pesticide contamination of water bodies.[27]

The trends observed in Punjab with respect to esophageal carcinoma incidence may provide us with a unique opportunity to learn more about the currently obscure exposures that cause esophageal carcinoma, by explaining why people in Punjab have the high rates of this disease. Using a case–control study design and techniques from epidemiology, we aim to identify the key exposures in the development of esophageal carcinoma in Punjab, with a focus on chemical toxicity.

This study will result in the identification of risk factors for the high occurrence of esophageal carcinoma in Punjab, so that measures for early detection, prevention, and control of esophageal carcinoma will be initiated with special recommendations to the NPCDCS program in the state.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.  Back to cited text no. 1
Three-Year Report of Population Based Cancer Registries 2012-2014. Available from: http://ncdirindia.org/NCRP/ALL_NCRP_REPORTS/PBCR_REPORT_2012_2014/index.htm. [Last retrieved on 2018 Oct 30].  Back to cited text no. 2
Abnet CC, Arnold M, Wei WQ. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology 2018;154:360-73.  Back to cited text no. 3
Mao WM, Zheng WH, Ling ZQ. Epidemiologic risk factors for esophageal cancer development. Asian Pac J Cancer Prev 2011;12:2461-6.  Back to cited text no. 4
Znaor A, Brennan P, Gajalakshmi V, Mathew A, Shanta V, Varghese C, Boffetta P. Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men 2003. Int J Cancer 2010;105:681-6.  Back to cited text no. 5
Phukan RK, Ali MS, Chetia CK, Mahanta J. Betel nut and tobacco chewing; potential risk factors of cancer of oesophagus in Assam, India. Br J Cancer 2001;85:661-7.  Back to cited text no. 6
Jussawalla DJ, Deshpande VA. Evaluation of cancer risk in tobacco chewers and smokers: An epidemiologic assessment. Cancer 1971;28:244-52.  Back to cited text no. 7
Gupta N, Barwad A, Rajwanshi A, Kochhar R. Prevalence of human papillomavirus in esophageal carcinomas: A polymerase chain reaction-based study. Acta Cytol 2012;56:80-4.  Back to cited text no. 8
Prasad MP, Krishna TP, Pasricha S, Krishnaswamy K, Quereshi MA. Esophageal cancer and diet-a case-control study. Nutr Cancer 1992;18:85-93.  Back to cited text no. 9
Guha N, Boffetta P, Wünsch Filho V, Eluf Neto J, Shangina O, Zaridze D, et al. Oral health and risk of squamous cell carcinoma of the head and neck and esophagus: Results of two multicentric case-control studies. Am J Epidemiol 2007;166:1159-73.  Back to cited text no. 10
Summary Report of Cancer Registries in Punjab and Chandigarh, India: 2014. Available from: http://tmcepi.gov.in/Publication.jsp#tab-2. [Last retrieved on 2018 Nov 15].  Back to cited text no. 11
Mittal S, Kaur G, Vishwakarma GS. Effects of environmental pesticides on the health of rural communities in the Malwa Region of Punjab, India: A review. Human and ecological risk assessment. Int J 2014;20:366-87.  Back to cited text no. 12
Thakur JS, Rao BT, Rajwanshi A, Parwana HK, Kumar R. Epidemiological study of high cancer among rural agricultural community of Punjab in Northern India. Int J Environ Res Public Health 2008;5:399-407.  Back to cited text no. 13
Singh G, Sharma RK. Alternatives to phosphine fumigation of stored grains: The Indian perspective. Himachal J Agricultural Res 2015;41:104-13.  Back to cited text no. 14
Bala A, Kaur K. An Exploratory study on selected household food storage practices of women in Punjab. J. Community Mobil Sustain Dev 2015;10:70-5.  Back to cited text no. 15
Doll R, Peto R, Wheatley K, Gray R, Sutherland I. Mortality in relation to smoking: 40 years' observations on male British doctors. BMJ 1994;309:901-11.  Back to cited text no. 16
McLaughlin JK, Hrubsec Z, Blot WJ, Fraumeni Jr JF. Smoking and cancer mortality among US veterans: A 26-year follow-up. Int J Cancer 1995;60:190-3.  Back to cited text no. 17
Ishikawa A, Kuriyama S, Tsubono Y, Fukao A, Takahashi H, Tachiya H, et al. Smoking, alcohol drinking, green tea consumption and the risk of esophageal cancer in Japanese men. J Epidemiol 2006;16:185-92.  Back to cited text no. 18
Freedman ND, Abnet CC, Leitzmann MF, Mouw T, Subar AF, Hollenbeck AR, et al. A prospective study of tobacco, alcohol, and the risk of esophageal and gastric cancer subtypes. Am J Epidemiol 2007;165:1424-33.  Back to cited text no. 19
International Agency for Research on Cancer. Alcoholic beverage consumption and ethyl carbamate (urethane). IARC Momographs 2007;96:1-5.  Back to cited text no. 20
Islami F, Fedirko V, Tramacere I, Bagnardi V, Jenab M, Scotti L, et al. Alcohol drinking and esophageal squamous cell carcinoma with focus on light-drinkers and never-smokers: A systematic review and meta-analysis. Int J Cancer 2011;129:2473-84.  Back to cited text no. 21
Salaspuro MP. Alcohol consumption and cancer of the gastrointestinal tract. Best Pract Res Clin Gastroenterol 2003;17:679-94.  Back to cited text no. 22
Meyer A, Alexandre PC, Chrisman Jde R, Markowitz SB, Koifman RJ, Koifman S. Esophageal cancer among Brazilian agricultural workers: Case-control study based on death certificates. Int J Hyg Environ Health 2011;214:151-5.  Back to cited text no. 23
Chrisman Jde R, Koifman S, de Novaes Sarcinelli P, Moreira JC, Koifman RJ, Meyer A. Pesticide sales and adult male cancer mortality in Brazil. Int J Hyg Environ Health 2009;212:310-21.  Back to cited text no. 24
Jansson C, Plato N, Johansson AL, Nyrén O, Lagergren J. Airborne occupational exposures and risk of oesophageal and cardia adenocarcinoma. Occup Environ Med 2006;63:107-12.  Back to cited text no. 25
Yildirim M, Kaya V, Yildiz M, Demirpence O, Gunduz S, Dilli UD. Esophageal cancer, gastric cancer and the use of pesticides in the southwestern of Turkey. Asian Pac J Cancer Prev 2014;15:2821-3.  Back to cited text no. 26
Thakur JS, Prinja S, Singh D, Rajwanshi A, Arora S, Prasad R, Parwana HK, Kumar R. Genotoxicity and adverse human health outcomes among people living near highly polluted waste water drains in Punjab, India. World J Pharmac Res 2014;4:895-908.  Back to cited text no. 27


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