Ann Thorac Surg 2003;76:S1367-S1369
© 2003 The Society of Thoracic Surgeons
Supplement: understanding disparities in cardiovascular and thoracic surgical outcomes in African-Americans
Geographical distribution and racial disparity in esophageal cancer
Allan Pickens, MDa*,
Mark B. Orringer, MDa
a University of Michigan Medical Center, Ann Arbor, Michigan, USA
* Address reprint requests to Dr Pickens, University of Michigan Medical Center, 362 Village Green Blvd, #202, Ann Arbor, MI 48105, USA
e-mail: allanp{at}med.umich.edu
Presented at the symposium on Understanding Disparities in Cardiovascular and Thoracic Surgical Outcomes in African Americans, San Diego, CA, Jan 30, 2003.
Esophageal cancer is a devastating disease that continues to have less than 10% 5-year survival despite advances in multimodality therapy. Esophageal cancer is the eighth most common cancer in the world, yet our understanding of this lethal disease is very limited [1].
The epidemiology of esophageal cancer is characterized by distinctly higher incidence in certain geographical locations and in specific races. These epidemiologic observations are important because of the potential contributions to the understanding of the etiology and pathogenesis of esophageal cancer. The etiology of esophageal cancer remains unknown.
An estimated 80% of primary esophageal neoplasms are malignant. Squamous cell carcinoma and adenocarcinoma are the most common histologic subtypes of esophageal cancer [2]. Both histologic subtypes have very different biological and epidemiologic profiles; consequently, esophageal squamous cell carcinoma and esophageal adenocarcinoma should be viewed as separate disease entities. Squamous cell carcinoma primarily occurs in the middle third of the esophagus, while adenocarcinoma predominately occurs in the lower third of the esophagus [3]. Squamous cell carcinoma remains the most common histologic subtype of esophageal cancer worldwide [1]. The incidence of squamous cell carcinoma has remained relatively stable. However, the incidence of adenocarcinoma has been rising over the past two decades. The incidence of primary esophageal adenocarcinoma has increased at a rate exceeding any other cancer [4]. The allocation of adenocarcinoma of the gastroesophageal junction to distal esophagus rather than gastric cardia may be influenced by increasing awareness of the epidemic of Barrett's esophagus [5].
Barrett's esophagus is metaplastic change of esophageal mucosa to "intestinelike" columnar epithelium. Patients with Barrett's esophagus have a 30- to 40-fold increased risk of developing adenocarcinoma, thus Barrett's mucosa should be considered a premalignant lesion. Nevertheless, most patients with esophageal adenocarcinoma do not have a previous diagnosis of Barrett's esophagus. The prevalence rates of Barrett's esophagus of 10% for the symptomatic population and less than 1% for the asymptomatic general population do not account for the recent dramatic increase in esophageal adenocarcinoma [2]. Barrett's esophagus is a link between benign gastroesophageal reflux and esophageal cancer, but no clear biological mechanism has been established. Lastly, there is no clear evidence that either medical or surgical treatment of reflux or Barrett's esophagus can prevent the development of esophageal cancer [2].
Both squamous cell carcinoma and adenocarcinoma of the esophagus are infrequent before 40 years of age, beyond which the incidence of each subtype continues to rise with each decade of life. Worldwide, males of all ages are more commonly affected than females. Males have a three- to fourfold greater risk than females for developing squamous cell carcinoma and a seven- to tenfold higher risk for developing adenocarcinoma [2].
Cancers of the esophagus exhibit a marked geographic variation in incidence. Areas of particularly high incidence of esophageal squamous cell carcinoma (expressed as crude incidence per 100,000) are as follows: China (21 per 100,000); South America (13 per 100,000); western Europe (11 per 100,000); southern Africa (10 per 100,000); Japan (9 per 100,000); and the former Soviet Union (8 per 100,000) [2]. Within each of these broad geographic areas are identifiable smaller regions in which the incidence may be 10 to 50 times higher. Such regions include central and northern China, southern Thailand, northern Italy, mountainous regions of Japan, costal parts of Iran, and certain French provinces. In the United States, high-incidence areas are the District of Columbia and the costal regions of southern states. The epidemiology of esophageal adenocarcinoma also demonstrates significant geographic variations. Developed countries in Europe and North America have higher incidence rates of esophageal adenocarcinoma. The incidence of esophageal adenocarcinoma has been reported to be rising in several areas of Europe including northern Europe (Sweden, Denmark, Norway), western Europe (England, Wales, Scotland), central Europe (Switzerland), and southern Europe (Italy). In North America, the United States and Canada have had the highest incidence rates [6]. The rate of increase in esophageal adenocarcinoma exceeds the rate for any other type of cancer [5]. Geographic areas of high prevalence must be identified in order to encourage early diagnostic testing, which encompasses esophageal brushing, flexible esophagoscopy, and evolving cytogenetics.
Esophageal cancer disproportionately affects certain ethnic groups and races. Esophageal cancer was reported as the fourth leading cause of death in African Americans [7]. The incidence of esophageal squamous cell carcinoma is more than fivefold higher among blacks (16.8 per 100,000) than among whites (3 per 100,000) in the U.S [8]. In contrast, esophageal adenocarcinoma is fourfold more prevalent in whites than in blacks in the U.S. Furthermore, the annual rate of esophageal adenocarcinoma rose from 0.7 per 100,000 to 3.2 per 100,000 over two decades, an increase of greater than 350% [4], which is illustrated in Figure 1. Such extreme racial disparity must be analyzed closely to identify risk factors.
It is very likely that risk factors for esophageal cancer exert different influences according to histologic type. Population based case control studies have identified risk factors for esophageal squamous cell carcinoma. Risk factors include: low income, moderate/heavy alcohol intake, smoking, infrequent consumption of raw fruit and vegetables, cultural practices, infection, and certain intrinsic esophageal diseases (Fig 2).
Much of the excess incidence in blacks has been attributed to lower socioeconomic status. Socioeconomic class appears to be an independent risk factor, and the risk is highest for those with annual incomes less than $10,000 [8]. The percentage of blacks living below this poverty level was reportedly higher than the percentage of whites. According to the 1980 U.S. census, 53.4% of blacks were 20% to 100% below poverty level compared with 2.1% of whites [9]. The contribution of socioeconomic status to racial differences in esophageal cancer incidence can be tested by adjusting for socioeconomic status to see if the differences diminish. Lack of individual socioeconomic status data for most esophageal cancer patients prevents such testing in a significant population. Aggregate population data from the U.S. census has been applied to individual cases. The U.S. census defines socioeconomic status according to median years of education, median family income, and percent of persons below the designated poverty level. The exact link between low socioeconomic status and esophageal cancer is unclear. Low socioeconomic class is a source for lifestyle and environmental factors including poor housing, workplace hazards, limited healthcare access, poor nutritional status, and exposure to infectious agents. A significantly higher risk of esophageal squamous cell carcinoma is noted among heavy drinkers of hard liquor (>35 drinks per week) [8]. The relationship between smoking and esophageal squamous cell cancer is less clear. The highest relative risk is present when cigarette smoking is combined with heavy hard liquor consumption. This observation implies synergy between chemical mutagens in tobacco and alcoholic drinks [2]. Several nutritional surveys of high incidence regions have suggested that diets rich in carbohydrates and low in protein, green vegetables, and fruit were associated with the development of esophageal cancer. Deficiencies of certain vitamins and minerals may also contribute (vitamin A, vitamin C, zinc) [10]. Infection (human papillomavirus) and intrinsic esophageal diseases (tylosis, Plummer-Vinson syndrome, achalasia, diverticula, stricture, radiation injury) produce esophageal mucosal changes that result in increased incidence of esophageal squamous cell carcinoma [2, 11]. The latter risk factors appear to be less important in the development of esophageal adenocarcinoma. Barrett's esophagus and obesity are the leading contributors to esophageal adenocarcinoma (Fig 2). Barrett's esophagus is considered a premalignant condition with no clear biological mechanism. The mechanism by which obesity predisposes to esophageal adenocarcinoma may be through increasing intraabdominal pressure and the subsequent risk of gastroesophageal reflux disease and its progression to the metaplastic premalignant state of Barrett's esophagus [4]. Further investigation is needed to define these risk factors and identify causal mechanisms [12].
Racial disparity in cancer survival has generally revealed a lower survival rate for black patients than white patients despite controlling for confounding variables such as age, sex, clinical factors, insurance status, and socioeconomic status. For esophageal cancer in general, the 5-year survival is 9% for blacks and 13% for whites according to the National Cancer Institute's Surveillance, Epidemiology, and End-Results Program. Furthermore, this survival difference was present despite similar rates of distant spread (26% distant spread for blacks and 25% distant spread for whites) [7]. This lower survival in blacks has been reported in the Veterans Affairs Medical Centers (VA), which eliminate many of the confounding variables because the faculty is the same and there is no insurance or fee requirement (Figs 3 and 4). Black veterans with esophageal squamous cell carcinoma were less likely than white veterans to undergo esophagectomy, whereas the use of radiation therapy and chemotherapy was increased.
The VA databases lacked detail concerning cancer stage at presentation. Esophageal squamous cell cancer mortality was higher for the black veterans. Black veterans with esophageal adenocarcinoma had lower odds of undergoing esophagectomy, but had similar utilization of radiation therapy and chemotherapy. Postulated explanations for the racial variation in patient treatment and outcome included: differences in severity of disease, unmeasured coexisting conditions, cultural differences in attitudes toward procedures and medical care in general, and systematic racial bias [7]. The determinants of survival disparity among races must be further investigated.
The basis for geographical distribution and racial disparity in esophageal cancer results from genetic and environmental factors. Histologic subtypes of esophageal cancer present very differently. The real importance of all of these epidemiologic observations relates to their potential contribution to our understanding of the etiology and pathogenesis of esophageal cancer. A more precise understanding of esophageal cancer may provide better surveillance and treatment.
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= squamous cell in black males; 
= adenocarcinoma in white males; 
= squamous cell in white males; • = adenocarcinoma in black males.)
