Cancer esophagus is a difficult-to-treat disease and strikes people in their middle or late middle age. The disease presents as difficulty in swallowing (dysphagia) solid food like rice and bread. Dysphagia to solids is of short duration.
Over a few weeks to months, a person cannot even eat or drink liquids and develop starvation and dehydration, unless an effective treatment is instituted.
Unfortunately, by the time difficulty in swallowing ensues, the disease has gone into an advanced stage and only palliative measures can be done to relieve symptoms temporarily. Cure at this stage of the disease is uncommon.
In the past, physicians practicing in Kashmir have appreciated the common occurrence of cancer esophagus in this region. Patients with cancer esophagus constitute a substantial percentage of consultations with the general physician, ENT specialists, and gastroenterologists.
To draw a point in this direction one may refer to surgical biopsies seen at Sheri-Kashmir Institute of Medical Sciences Soura Srinagar Kashmir over 3 years (December 1982 to December 1985). Of the 8060 surgical biopsy specimens evaluated in this period, 2340 (29.0%) were diagnosed as having cancer of various organs.
68.7% of these cancers had occurred in the gastrointestinal tract namely- the esophagus, stomach, colon, pancreas, and gall bladder. Around 46.1% of gastrointestinal cancers were situated in the esophagus.
These exceptionally high figures of cancer esophagus in the surgical biopsy specimens speak volumes of the load of this disease in Kashmir (Indian J Pathology/Microbiology.1990; 33:118-23).
Recently several reports have shown the constancy of these data and pointed to the high occurrence of cancer esophagus in Kashmir. However, these data are/were crude and could not be presented to the rest of the world and international organizations to draw attention to further studies in this area.
To study a load of cancer in a community we need incidence (new cases per 100,000 per year) of the disease by collecting data more scientifically.
We performed a study on the incidence of cancer esophagus in the valley (Gut 1992;33(1):11-5). The entire population of Kashmir was studied, and all new cases of esophageal cancer were recorded.
1515 cases of esophageal cancer occurred over 3 years from July 1986 to June 1989. Of these 1050 cases were men and 465 cases were women. The disease occurred in the age group of 45-70 years. The crude incidence rate of the disease was 22.6 per 100,000 per year in men and 11.5 per 100,000 per year in women.
The age-standardized incidence for the disease was 44 per 100 000 per year in men and 30 per 100,000 per year in women. The truncated incidence rate (35 to 64-year age group) was 108.2 per 100,000 per year in men and 70 per 100,000 per year in women. These figures were 3 to 6 times higher than those recorded by cancer registries in Bengaluru, Madras, and Mumbai.
These high incidence figures were comparable to the incidence of esophageal cancer occurring in the northern regions of Iran, Turkmenia, Kazakhstan, Uzbekistan, and China.
An esophageal Asian cancer belt has been defined as extending from northern Iran, Mongolia, Central Asia, and Japan. Our study showed that Kashmir borders this cancer belt in the southern region. At the same time, Kashmir also had an unprecedentedly high incidence of gastric cancer.
One of the hallmarks of this study was a varied incidences of esophageal cancer in different districts and various ethnic groups in Kashmir.
The incidence rates for esophageal cancer in the Southern District of Kashmir, Islamabad were 4.1 to 5.4 times higher in men and 1.5 to 2.0 times higher in women than those for the Northern district, Kupwara. The incidence rates for esophageal cancer in Muslims, Hindus, and Sikhs were different.
These figures for the first-time established Kashmir as having a high incidence of esophageal cancer.
Considering this high incidence of esophageal cancer in Kashmir, another study was done to define the evolution of this disease and this study showed that the esophagus of people of Kashmir is abnormal in most of the adult population (Indian Journal of Cancer 1987;24(4):232-41).
This study was done in otherwise healthy volunteers who opted to undergo an assessment of their food pipe for the promotion of scientific knowledge.
Of the 107 volunteers studied, a chronic form of esophagitis (inflammation of the esophagus) was seen in 2/3rd of the subjects. These subjects had no symptoms related to their esophagus. Around 1/3rd of the subjects had more advanced changes in their esophagus namely mucosal acanthosis, atrophy, and dysplasia.
Dysplasia is a pathological state that occurs in tissues before cancer is formed. Many tissues in the body pass through various grades of dysplasia eventually leading to cancer. Around 10% of the volunteers studied had changes of dysplasia in their esophagus.
These data have been of value in understanding the pathogenesis of cancer of the esophagus in Kashmir. We believe that a chronic form of esophagitis exists in a majority of the population in Kashmir. Esophagitis leads to dysplasia and eventually culminates into cancer.
This process can take up to 20 to 30 years. Over these years persons have had no symptoms related to this form of esophagitis and dysplasia. Even early cancer once developed cause no symptoms.
The symptoms only occur when cancer blocks the lumen of the esophagus and does not allow swallowed food to pass into the stomach. At this stage, the disease is advanced and only amenable to palliative treatment and not cures.
Kashmir is an ethnically distinct population with special personal and dietary habits. These include intake of sundried cruciferous vegetables of the brassica family (Hakh), pickled vegetables (Aanchar), dried or smoked fish (Hokh / fur-gard), cakes made of chilies, garlic, and cardamom (Wur), and above all large quantities of hot salt tea (Noon chai).
Smoking in the Valley is also distinctive and involves the use of a hubble-bubble (Jajeer). Could any of these habits of the people lead to a high incidence of esophageal cancer in the Valley? Although speculated, there were no scientific data to prove the point that one or more of the above personal or dietary factors could be implicated in the high incidence of esophageal cancer in the Valley.
A case-controlled study in patients with esophageal cancer was done to define if there are any personal or dietary factors within explain the high incidence of esophageal cancer in the valley (Thesis Submitted to Sheri Kashmir Institute of Medical Sciences Srinagar Kashmir.1993).
For this, a detailed assessment of 100 patients with proven esophageal cancer and compared with 200 age and sex-matched controls. The controls were relatives of such patients or healthy persons from the same localities. Patients with esophageal cancer when compared to controls had less consumption of fresh fruits and vegetables and increased intake of pickled vegetables (Aanchar), chilly cakes (Wur), smoked fish, and sun-dried vegetables.
In addition, patients with cancer when compared to controls had consumed larger quantities of salt tea (Noon chai). Also, patients with cancer were more often smokers and had smoked larger amounts of tobacco through hubble-bubble (Jajeer).
To reduce the impact of confounding factors we performed a multivariate analysis and based on this the factors which had an association with esophageal cancer were: 1) intake of more than 5 cups of salt tea per day, 2) smoking, 3) less intake of fresh fruits (<6 times per month). Patients who consume salt tea more than 5 cups /day had an odds ratio of 6 for the development of the disease. It was the amount of tea, which was important rather than the temperature at which it was drunk.
While analyzing the above data we must caution that the nature of the study (case-controlled) does not conclusively prove the cause-and-effect relationship of these dietary and personal habits to esophageal cancer in the Valley.
To prove the cause-and-effect relationship of one or more of the implicated factors we had planned longitudinal and intervention studies but were abandoned for reasons beyond our control.
However, these data at best could be an eye-opener and demand an inquiry as to why salt tea should lead to such a high incidence of esophageal cancer. With the help of several international agencies analysis of the various food items special to Kashmir were analyzed (Carcinogenesis 1992; 13(8): 1331-5).
Analytical data on aliphatic amines and nitrates from the most used fresh and sun-dried vegetables, red chilies and widely consumed beverages, and salted tea consumed by the inhabitants of Kashmir were done. Exposure estimates for the adult population showed that high consumption of boiled Brassica vegetables leads to a high nitrate intake of 237 mg/day.
The frequent consumption of hot salted tea resulted in exceptionally high exposure to methylamine (1200 micrograms/day), ethylamine (14,320 micrograms/day), dimethylamine (150 micrograms/day), and diethylamine (400 micrograms/day).
The indiscriminate use of red chilies in the area leads to exposure to dimethylamine (280 micrograms/day), pyrrolidine (517 micrograms/day), and methylbenzylamine (40 micrograms/day). This was the first report where chronic exposure to methylbenzylamine has been shown in a population at high risk of esophageal cancer.
Salted tea prepared by adding sodium bicarbonate showed high methylating activity (equivalent to 3-PPM N-methylnitrosourea) upon in vitro nitrosation (Carcinogenesis 1992;13(11):2179-82). Pure caffeine treated under conditions of the tea preparation formed caffeidine and caffeidine acid.
The formation of two new compounds mono-nitrosocaffeidine, an asymmetric nitrosamine, and dinitrosocaffeidine, a N-nitrosamide was reported on in vitro nitrosation of caffeidine. Mononitrosocaffeidine was also found after nitrosation of the typical Kashmir tea.
The nitrosation of caffeidine acid produced N, N’-dimethyl-parabanic acid, mononitrosocaffeidine, and N-N’-dimethyl-N-nitrosourea. Because of the well-known structure-activity relationships of these N-nitroso compounds, their possible endogenous formation due to high consumption of salted tea may be a critical risk factor for the high occurrence of esophageal and gastric cancers in Kashmir).
Another important recently published study by me and my colleagues showed that esophageal cancer in Kashmir was in part related to infection with Human Papilloma Virus (HPV 16 & 18) and a significant percentage of patients had a mutation in the p53 tumor suppression gene (Cancer Letters 2005).
Although the story of esophageal cancer in the Valley has partially unfolded yet will take years of painstaking hard work to collect epidemiological data to implicate any one or more of the food and personal habits in its causation. Also, we need more basic work in the laboratories to screen a wide range of food items for possible carcinogens.
Epidemiologists, health planners, and society need to come up with major health plans to study, define and control this disease. Oncologists need to join to gain experience with this disease and give their best to unfortunate patients who suffer from this cancer.
When any of the items are confirmed to cause this cancer mass educational program for the public is needed to reduce the incidence of this devastating disease in this community.
Till that time, it is safe to propose the following advice to the inhabitants of the Valley: i. Limit intake of salt tea to less than 5 cups per day, ii. Stop any form of smoking, iii. Take fresh fruits at least once a week.
(Khuroo is a former Professor & Head of Gastroenterology and Chairman of Dept. Medicine, SKIMS.)
DISCLAIMER: The views and opinions expressed in this article are the personal opinions of the author.
The facts, analysis, assumptions and perspective appearing in the article do not reflect the views of GK.