Epidemiologic Aspects of Esophageal Cancer in Saudi Arabian Patients
1985; King Faisal Specialist Hospital and Research Centre; Volume: 5; Issue: 2 Linguagem: Inglês
10.5144/0256-4947.1985.69
ISSN0975-4466
Autores Tópico(s)Folate and B Vitamins Research
ResumoOriginal ArticlesEpidemiologic Aspects of Esophageal Cancer in Saudi Arabian Patients Magid H. AmerMD, FRCS, FRCP(C), FACP Magid H. Amer Head, Division of Medical Oncology, Department of Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia Search for more papers by this author Published Online:1 Apr 1985https://doi.org/10.5144/0256-4947.1985.69SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutABSTRACTABSTRACTBetween September 1978 and December 1982, 98 patients with histologically confirmed squamous cell carcinoma of the esophagus, referred to King Faisal Specialist Hospital and Research Centre, were studied. There were 59 (60%) males and 39 (40%) females with a mean age of 56.8 years. One third of the males (36%) were either Bedouin or farmers, while all females were housewives. Half of the patients (48%) were of low socioeconomic status. Twenty-two patients (22%) had evidence of cachexia, and 35 (35%) had a clinical picture of mild vitamin A deficiency. Nutritional assessment showed malnutrition for years preceding cancer diagnosis. All patients reported consumption of Arabic coffee averaging 10 cups a day. Twenty cases (20%) were referred from Al-Qaseem area alone; in contrast, only 4% of total cancer patient referrals to KFSH were from this area (P < 0.05). When compared to population density, the highest prevalence of esophageal cancer was also noted in Al-Qaseem compared to other areas in the Kingdom (P < 0.05). It has been suggested that the high incidence of esophageal cancer in this region may be related to the heavy water contamination in this area by such impurities as methane gas and petroleum oils. Malnutrition, particularly vitamin A deficiency, as well as thermal and mechanical injury to the esophageal mucosa by excessively hot coffee and food intake, may have promoted such malignancy.INTRODUCTIONEpidemiologic studies using different sources of information have demonstrated geographic differences in incidence as well as relative frequencies of esophageal cancer. In Western populations, the reported yearly incidence among affluent males is less than 5/100,000. Major risk factors in such groups are mainly alcohol abuse and heavy smoking.1–3 Worldwide, there is a striking geographic and ethnic variability of this disease. The highest prevalence exceeds 100/100,000 in areas such as Kazakhstan Province in the USSR, Northern Iran, Henan Province in China, and the Southern Transkei District in South Africa.4 In some localities, a hundredfold or more differences in mortality have been noted within a radius of several hundred miles. For example, in Northern China, mortality from esophageal cancer ranges from 1.4/100,000 to 140/100,000 within a small area. Similar variations in cancer of the gullet have been found in chickens within that region.5 Other demographic variations have been described within the Caspian region of Iran.6 No evidence for a role of alcohol abuse has emerged from these areas. However, mutagenic pyrolysis products of opium and tobacco are ingested in Iran and Transkei, respectively.7 Some evidence of a suboptimal geochemical environment, specifically mineral element deficiencies, has emerged from Transkei,8 Iran,9 China,5 and even the United States.10 It is possible that mineral element deficiencies may account for an increased fungal invasion and mycotoxin contamination of corn as well as other food products.11 Other dietary deficiencies and eating habits have been claimed to be contributing factors.12Esophageal cancer is relatively common in Saudi Arabia. It accounts for 5% to 6% of all cancer patient referrals to KFSH and ranks as the fifth commonest tumor in both males and females.13 Recently, we have noticed that a large percentage of esophageal cancer patients are referred from Al-Qaseem, in the North Central part of the Kingdom. A study was conducted to test the space clustering of this disease and to determine those factors which may have contributed to such observations.MATERIALS AND METHODSKing Faisal Specialist Hospital and Research Centre (KFSH) is a multispecialty referral hospital and the main cancer treatment center in Saudi Arabia; an average of 1300 new cancer patients are referred each year. Between September 1978 and December 1982, 98 consecutive and unselected patients with histologically confirmed squamous cell carcinoma of the esophagus referred to the Oncology Department, KFSH, and seen by the author, were studied. All patients had a detailed history and clinical examination with special attention to occupational history, residential location, social habits, and parental history of cancer.Age was defined at the time of initial diagnosis. Residency location referred to one of the five main provinces in Saudi Arabia (Fig. 1). The Central Province includes Riyadh, Al-Kharj, Dawadmi, and Aflag. Medina, Yanbu, Jiddah, Makkah, Taif, and Baha are included in the Western Province, while Hail, Tabuk, Ar Ar, and Al Jowf are the main cities in the Northern Province. The Southern Province includes Abha, Bisha, Najran, and Jizan. Dammam, Hofuf, and Qatif are included in the Eastern Province. The Al-Qaseem and Buraydah areas are defined as separate regions.Fig. 1. Map of Saudi Arabia showing different geographic areas, patient distribution.Download FigureTobacco consumption was analyzed both in terms of presence or absence of smoking history and the number of cigarettes consumed a day. Patients who smoked fewer than 20 cigarettes/day or its equivalent for 30 years were considered as light smokers and those who consumed cigarettes above this level as heavy smokers.Socioeconomic status was determined based on patients' living standards. Those who lived in small houses or tents, without electricity, clean running water, or properly connected sewage systems were considered in the low socioeconomic class, regardless of their income. They included some Bedouin and farmers. Other patients were classified as middle or upper class, depending on their gross yearly income of less than or more than 100,000 Saudi riyals (equivalent to U.S. $30,000).Data were obtained on concomitant medical problems, nutritional status, presenting symptoms, type of therapy, and subsequent survival. All patients had a complete blood count, multiphasic blood chemistry screen, chest radiograph, and esophogram. Most patients had radionuclide liver and bone scanning and a few had computerized tomographic whole body scanning. Histologic confirmation was obtained during endoscopic examination with fiberoptic, forward viewing esophagogastroscopy with guided biopsy. Location of the primary esophageal cancer was defined during initial endoscopy as an upper-third esophageal tumor if it was within 20 to 28 cm from the incisor teeth, middle-third if it was between 29 and 36 cm, and lower-third if it was more than 37 cm. Twenty-nine patients completed a detailed questionnaire on demographic data and personal habits, particularly smoking, drinking, and dietary status 20 years ago and at the present.The chi-square statistical test with one degree of freedom was used to differentiate between two or more variables; Student's t-test (in two tails of the t distribution with two less than the total number as a degree of freedom) was used to differentiate between different means.RESULTSBetween January 1980 and December 1983, 4761 patients with cancer were referred to KFSH and entered into the hospital Cancer Registry (Table 1). Esophageal cancer accounted for 5% of all malignancies and was the fifth commonest tumor in both males and females. Among these referrals as well as others, 98 consecutive and unselected patients with histologically confirmed squamous cell carcinoma of the esophagus referred to the Oncology Department at the hospital and examined by the author, were seen during the interval between September 1978 and December 1982. Epidemiologic data on this group of patients form the basis of this study.Table 1. Cancer patient referrals to King Faisal Specialist Hospital between 1980 and 1983Table 1. Cancer patient referrals to King Faisal Specialist Hospital between 1980 and 1983The pattern of patient age in relation to sex is illustrated in Fig. 2. There were 59 (60%) males and 39 (40%) females. Most patients were in their fifth or sixth decades, with a mean age of 56.8 years compared to 45.9 years for other malignancies. Fourteen patients (14%) had carcinoma in the upper esophagus, 33 (34%) in the middle third, and 51 (52%) in the lower third, with no direct extension into the cardiac end of the stomach. During endoscopy no gross evidence of reflux esophagitis or esophageal erosion was seen at the gastroesophageal junction, nor was any mucosal atrophy noted. However, no biopsy was taken from the surrounding normal mucosa to exclude such possibility.Fig. 2. Age and sex distribution of all patients with esophageal cancer compared to other malignancies. The top numbers show total patients at each age group. Data on patients with other malignancies were derived from the Hospital Cancer Registry on patients seen during 1983.Download FigureThe majority of male patients, 21 (36%), were either Bedouin or farmers. All female patients were housewives. Half of all patients, 47 (48%), were of low socioeconomic status (Table 2). These figures are no different from patients with other malignancies. Family history of cancer was found in only one patient.Table 2. Pattern of esophageal cancer patients referred from Al-Qaseem, Saudi Arabia, compared to other locationsTable 2. Pattern of esophageal cancer patients referred from Al-Qaseem, Saudi Arabia, compared to other locationsClinical assessment of nutritional status and serum albumin levels were obtained in all patients at the time of admission. There were 11 patients with esophageal cancer whose average weight was over 60 kg, while 22 (22%) patients averaged less than 40 kg. Thirty-five patients had clinical evidence of mild vitamin A deficiency, mainly dryness of bulbar conjunctiva and/or dryness and hyperkeratosis of the skin. Unfortunately, vitamin A levels were not determined in these patients. None of the patients showed clinical evidence of riboflavin, nicotinic acid, or vitamin C deficiencies. Cachexia was more frequent among patients with esophageal neoplasms than among those with other malignancies. However, admission serum albumin was not significantly different among either group; the mean level was 3.6 gm/dl.A detailed nutritional survey in 29 patients indicated poor dietary habits with malnutrition for years preceding cancer. Five (17%) patients consumed meat every day, three (10%) every two or three days, 17 (59%) once a week, and four (14%) once a month. Poor vitamin intake from inadequate vegetables or fruits in the diet was also noted in the majority of patients (83%). Some ate vegetables or fruits once a week (19), every month (3), or not at all (2). Eighteen patients were either light (12) or heavy (6) smokers. None of the esophageal cancer patients admitted the consumption of alcohol. Alcohol-related hepatitis, pancreatitis, gastritis, and neuropsychiatric problems likewise were not seen. All patients admitted the consumption of Arabic coffee at an average of 10 cups a day, range from 1 to 30 cups.Twenty-six (27%) patients were referred from Riyadh and vicinity, 20 (20%) from Al-Qaseem, 43 (44%) from other locations, and in nine patients no information was obtained (Table 3). Because an apparent increase in frequency of esophageal cancer from Al-Qaseem might be due to increasing cancer patient referrals in general or higher population density in this region, these factors were investigated further. Table 3 demonstrates the total number of esophageal cancer patients seen in relation to total cancer patient referrals and population density. Such high referral of esophageal cancer patients in this study from Al-Qaseem (20%) is in marked contrast to the only 4% contribution from Al-Qaseem and vicinity to all cancer patient referrals to KFSH (P < 0.05). When compared to population density, the highest prevalence was also noted in this region compared to other areas in the Kingdom (P < 0.05).Table 3. Esophageal cancer patient referrals according to residency location and population density in Saudi ArabiaTable 3. Esophageal cancer patient referrals according to residency location and population density in Saudi ArabiaWhen patients from Al-Qaseem were compared to those referred from other locations, there were no statistical differences noted between the two groups, especially in regard to patient age, sex, occupation, socioeconomic status, family history of cancer, and nutritional status (Table 2). However, wells and natural springs are the main sources of drinking water in Al-Qaseem but provide only 54% of the drinking water supply in other locations. All the population in this region consume water derived from old constructed wells, natural springs, and water pumps tapping underground water. The major sources of drinking water are numerous unchlorinated, privately owned wells dug at a depth of at least 10 meters, shared by the same families for years and by a few for decades. Many patients have complained of water impalatability and excessive hardness. Some have observed the presence of combustible gas bubbling through the water. Many have fitted their water tanks with vents to let gases escape and occasionally ignite the outlet or boil the water to correct its taste. The majority have indicated that such water impurities have markedly diminished during the last few years. Recently, the Buraydah Municipal Water project has extended the public water supply to most of the population living within the city limits. The municipal water project supplies water derived from deep underground bedrock by 14 wells at a depth of over 300 meters.DISCUSSIONThe remarkable geographic and regional variations in the incidence of esophageal cancer have been documented in many parts of the world.4 In general, the male age-standardized incidence rate for esophageal cancer reported from affluent Western populations is less than 5/100,000.1 A higher prevalence of this disease, over 100/100,000, was reported in several areas such as the USSR, Iran, China, and South Africa.4In Saudi Arabia, esophageal cancer is relatively common, with marked regional variations within the Kingdom. This observation was based on a relative frequency analysis of patients with this disease referred to KFSH, which is the main cancer treatment center in the Kingdom. Obviously, the relative frequency data gathered in this manner may contain inaccuracies, compared to the actual incidence derived from a recognized National Cancer Registry. For instance, the increased number of cases referred from one area compared to another may be due to a real increase in the incidence of malignancy but also may reflect improved medical care of the population with earlier detection of the disease at this location. However, with the lack of a National Cancer Registry, we had to rely on hospital statistics in making any analysis.Our patients appear to be younger than those reported in other areas of the United States and Western countries, where 65% to 82% of esophageal cancer patients are over the age of 60 at the time of diagnosis.14,15 In our series, however, 51% were younger than 60 years old at the time of diagnosis. Such a trend toward occurrence of esophageal cancer in younger people perhaps suggests an earlier exposure to environmental carcinogens.The preponderance of male cases over female cases generally seems most evident in the Western population, with a male-to-female ratio of 3:1, compared to 3:2 in high risk areas such as in Iran.16 It has long been known that in all of the highest incidence areas of the world, the sex ratio tends to approach unity.17 In this study, male-to-female ratio is 3:2, which may suggest an equal exposure of both sexes to the same environmental factors.Familial occurrence of esophageal cancer is relatively uncommon except in families of patients with a hyperkeratotic condition called tylosis. In this series none of our patients had this disease, and only one had a familial history of other malignancies.The combination of excessive alcohol consumption and heavy cigarette use has been suggested as a significant risk factor.2,14, 18 Fuel oils and poly-cyclic aromatic hydrocarbons found in alcoholic beverages have been implicated as etiologic factors in the development of esophageal cancer.19 Another theory linking alcohol to this disease refers to the ability of alcohol to increase absorption of potentially carcinogenic hydrocarbons.19 However, only a small percentage of our patients were heavy smokers, and none admitted the consumption of alcohol.An endoscopic survey in a population at high risk for esophageal cancer in Northeast Iran showed an association between a high prevalence of asymptomatic chronic esophagitis and a high incidence of esophageal cancer.16 Such esophagitis is characterized by irregular friable mucosa with varying degrees of edema, hyperemia, and leukoplakia but without ulceration, and it usually involves the middle and lower third of the esophagus without invasion of the cardiac region of the stomach. This is in contrast to esophagitis in low-risk populations in Europe, which is characterized by erosions and ulcerations and usually involves the gastroesophageal junction because of reflux. Chronic esophagitis is usually followed by mucosal atrophy and then squamous metaplasia, which has been proposed as a possible precancerous lesion.16,20–22 Similar events were previously noted in experimental models23,24 as well as in large epidemiologic studies in China.12 It has been postulated that thermal injury resulting from drinking very hot beverages and physical injury caused by ingesting very coarse food could be an additional risk factor for the development of these precursor lesions.12 Most patients in this study drank more than 10 cups of extremely hot Arabic coffee a day. The Saudi habit of eating food steaming hot may also contribute to mucosal atrophy secondary to thermal injury, although it has not been established that cancer can be induced in this way.During recent years there has been a growing awareness about an association between nutrition and cancer causation. In this study, dietary habits among this patient population during the last several decades has been relatively stable. Until recently, diet in Saudi Arabia has been mainly cereal, meat, milk, dates, and occasional vegetables or fruit. Fish was rarely consumed and canned food was never eaten. Eating habits have dramatically changed during the last few years with the introduction of modern food processing, preparation, and storage and a greater drive toward self-sufficiency in regard to agricultural products. However, such changes, although they may affect future generations, could hardly have influenced cancer initiation and promotion in the patients studied.In a recent report,17 main dietary staples were correlated with relative frequency of esophageal cancer. Corn and/or wheat were the main dietary staples in populations with high risk of developing esophageal cancer.25 A deficiency of nicotinic acid is the outstanding nutritional feature of corn eating populations due to the deficiency of the precusor tryptophan. Clinically, the esophageal mucosa in pellagra is usually intensely hyperemic and sometimes edematous with occasional ulceration and dysphagia. Signs of esophagitis were also found in 80% of the population at high risk of esophageal cancer in Iran.16 In this study, there was no clinical evidence of pellagra among patients with esophageal cancer, nor was there any endoscopic picture of esophagitis or ulceration. Moreover, a corn diet is rarely consumed in Saudi Arabia.Adequate vitamin A intake is essential to maintain the integrity of epithelial cells. Vitamin A or other retinoid supplementation has inhibited carcinogenicity in animals.26–28 Decreased plasma vitamin A levels have been noted in patients with squamous cell cancer of the oral cavity, pharynx,29 lung,30 and esophagus.31 The inadequate vegetable consumption among our patient population for years preceding cancer diagnosis may be responsible for clinical hypovitaminosis A and may have enhanced the possibility of cancer induction.Some trace elements have a carcinogenic or mutagenic potential, such as beryllium, cadmium, chromium, cobalt, lead, nickel, and iron carbohydrate complexes. The role of these trace elements in the causation of esophageal cancer is unknown. However, a recent report has linked molybdenum deficiency and lesions involved with esophageal cancer in Linhsien County in China32 and the Transkei area in South Africa.8 Mineral element deficiencies were also attributed to the noticeable increase in fungal invasion and mycotoxin contamination of corn in areas where there is a high risk of developing esophageal cancer.11,33 At Al-Qaseem, the high concentration of metalliferous minerals such as silver, gold, and copper34 may suggest the presence of other minerals and trace elements in that region. Unfortunately, no accurate geologic data are available, especially on trace elements in Saudi Arabia except in a few scattered locations; none are available from Al-Qaseem. Such information would be of great value in determining any correlation between the disease and the presence or deficiency of these elements.The high referral rate of esophageal cancer patients from Al-Qaseem between September 1978 and December 1982 was noted again during 1983 and recorded by the KFSH Cancer Registry. Six of 60 patients (10%) referred from this region had squamous cell carcinoma of the esophagus, compared to 54 of 1366 (4%) patients referred from other areas in the Kingdom (P < 0.05). The highest referral rate per 100,000 population per annum, based on Registry statistics during 1983, was noted in Al-Qaseem region (1.77), followed by the Eastern Province (1.16), and Central Region (1.02), all known for their proximity to underground oil reserves (Fig. 1), compared to Southern province (0.12) (P < 0.05) (Table 3). The actual national prevalence rate may be even higher, especially if one takes into consideration other unreported cases or those patients referred to other centers.When esophageal cancer patients referred from Al-Qaseem were compared with those referred from other locations, no statistical differences were noted between the two groups except for the type and source of drinking water. Water analysis at the Ministry of Agriculture**Personal communication, ARAMCO, Riyadh, Saudi Arabia. confirmed the presence of traces of methane gas mixed with underground water. However, the quantity was too small to be commercially valuable. Further water analysis at the Faculty of Pharmacy, Riyadh University, showed a high solid content in four out of six samples collected.35 Nonpathogenic Pseudomonas organisms were grown from three samples, but no other bacteria, such as Escherichia coli, fecal streptococci, or Clostridium perfringens grew noticeably; which excluded the possibility of sewage contamination. Traces of mineral oils were detected in five of six samples analyzed. The possibility of water contamination by petroleum oils needs further examination.It is possible that water contamination by factors such as petroleum oils, polycyclic hydrocarbons, or trace elements may be the main initiating factor for the development of esophageal cancer. Malnutrition, particularly vitamin A deficiency, as well as thermal and mechanical injury to esophageal mucosa by excessively hot coffee and coarse food intake, may promote such malignancy. The high prevalence of this disease at Al-Qaseem, Eastern Province, Riyadh and vicinity, might be explained by their proximity to oil wells, compared to other areas such as in Jizan at the Southern Province. This may also explain the particular distribution of this disease in countries such as Iran, China, and the USSR. Extreme variations in incidence and mortality of this disease within a radius of 100 miles may be due to the extreme variation in water components depending on the geochemical structure of each particular location. Nearly equal distribution of cancer among males and females, as well as the increase of cancer of the gullet among chickens in high-risk areas, may be attributed to exposure to the same carcinogenic factor(s) possibly via contaminated water. Obviously, further studies are needed to refute or accept such a hypothesis.ARTICLE REFERENCES:1. 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Ministry of Finance and National Economy, Kingdom of Saudi Arabia: Statistical Year Book. Jeddah, Saudi Arabia, Dar Okaz for Printing and Publishing, 1980, pp 22–151. Google Scholar Previous article Next article FiguresReferencesRelatedDetails Volume 5, Issue 2April 1985 Metrics History Published online1 April 1985 KeywordsEsophageal neoplasmsEpidemiologySaudi ArabiaInformationCopyright © 1985, Annals of Saudi MedicinePDF download
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