Elsevier

Cancer Epidemiology

Volume 41, April 2016, Pages 88-95
Cancer Epidemiology

The epidemic of oesophageal carcinoma: Where are we now?

https://doi.org/10.1016/j.canep.2016.01.013Get rights and content

Highlights

  • Between 1973 and 2001, oesophageal adenocarcinoma was one of the fastest rising cancers in many developed countries.

  • Although the rate of increase has slowed, incidence of oesophageal adenocarcinoma continues to rise and will constitute an increasingly large health burden in the years ahead.

  • Men are seven times more likely than women to develop oesophageal adenocarcinoma; the reasons for the striking sex disparity remain unknown.

  • Gastro-oesophageal reflux disease, obesity and cigarette smoking are the main risk factors for oesophageal adenocarcinoma.

  • In contrast, the incidence of oesophageal squamous-cell carcinoma continues to decline in Western populations.

  • 5-year survival rates for oesophageal cancer remain less than 20%.

Abstract

Since the early 1970s, the incidence of oesophageal adenocarcinoma has increased dramatically in most Western populations. In contrast, the incidence of oesophageal squamous-cell carcinoma has decreased in these same populations. Epidemiological studies conducted over the past decade have provided great insights into the etiology of oesophageal cancer. These studies have identified gastro-oesophageal reflux disease, obesity and cigarette smoking as risk factors for oesophageal adenocarcinoma, while use of nonsteroidal anti-inflammatory drugs and infection with Helicobacter pylori are associated with reduced risk of oesophageal adenocarcinoma. For oesophageal squamous-cell carcinoma, alcohol and cigarette smoking are the two major risk factors underlying most cases. This review combines a synthesis of these studies with an analysis of data from the United States National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program to discuss the change in incidence of oesophageal cancer and summarize current knowledge of risk factors.

Introduction

Esophageal cancer is a relatively common and highly fatal malignancy. Worldwide, oesophageal cancer is the eighth most common cancer (456,000 new cases in 2012; 3% of all cancers in 2012) and the sixth most common cause of cancer-related death (400,000 deaths in 2012) [1]. The highest incidence rates of oesophageal cancer are seen along two geographic belts, one from north central China through the central Asian republics to northern Iran, and one from eastern to southern Africa (Fig. 1).

There are two main histological subtypes of oesophageal cancer: oesophageal adenocarcinoma and oesophageal squamous-cell carcinoma. Worldwide, oesophageal squamous-cell carcinoma is the most common oesophageal cancer subtype (representing 87% of all cases of oesophageal cancer in 2012 [2]). While this is due largely to high rates in many developing countries, incidence rates of oesophageal squamous-cell carcinoma are significantly higher than rates of oesophageal adenocarcinoma in 90% of all countries presented in GLOBOCAN [2].

There has been a dramatic shift in the epidemiology of oesophageal cancer in Western populations such that oesophageal adenocarcinoma has become the predominant subtype of oesophageal cancer in North America, Australia and Europe [3], [4], [5]. Epidemiological studies have implicated gastro-oesophageal reflux disease, obesity and cigarette smoking as the main risk factors for oesophageal adenocarcinoma. Together, these three risk factors account for over 70% of all cases of oesophageal adenocarcinoma in Western populations [6], [7].

Barrett’s oesophagus, a condition in which the normal squamous mucosa of the oesophagus is replaced by columnar intestinal epithelium, is the only precursor lesion for oesophageal adenocarcinoma. Barrett’s oesophagus is present in up to 15% of individuals with frequent symptoms of gastro-oesophageal reflux disease, and in 1–2% of the general adult population [8]. Compared to the general population, patients with Barrett’s oesophagus have at least 10-fold higher risk for oesophageal adenocarcinoma [9]. Consequently, patients with Barrett’s oesophagus are entered into a program of periodic endoscopic surveillance. However, although endoscopic surveillance every 3 years is recommended for patients with known nondysplastic Barrett’s oesophagus, the absolute risk of oesophageal adenocarcinoma in Barrett’s oesophagus is relatively low (0.33% per year) [10] and it remains unclear whether these patients benefit from long-term surveillance in terms of a reduction in overall mortality or risk of death from oesophageal adenocarcinoma [11], [12], [13], [14], [15], [16], [17].

During the period when rates of oesophageal adenocarcinoma were increasing dramatically in many Western populations, rates of oesophageal squamous-cell carcinoma declined in these same populations; however, oesophageal squamous-cell carcinoma remains the predominant oesophageal cancer subtype in Asia, Africa and South America. Heavy alcohol consumption and cigarette smoking are the main risk factors for oesophageal squamous-cell carcinoma, accounting for 80% and 40% of oesophageal squamous-cell carcinomas in men and women, respectively [18]. Oesophageal squamous dysplasia is the precursor lesion for oesophageal squamous-cell carcinoma [19]. Although treatment effectiveness has improved during the past decade, survival rates for oesophageal cancer remain poor. This review will focus mainly on the descriptive epidemiology and risk factors for oesophageal adenocarcinoma.

Section snippets

Recent trends in the incidence of oesophageal adenocarcinoma in Western populations

A seminal paper published in 2005 reported that oesophageal adenocarcinoma was one of the fastest rising cancers in the United States between 1975 and 2001 [3]. In subsequent analyses using data from the United States National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program to quantify rates of change in the incidence of oesophageal cancer over time, it was shown that the incidence of oesophageal adenocarcinoma in the United States increased at a rate of 8% per

Prognosis for oesophageal adenocarcinoma

In the United States, the overall 5-year survival rate for patients diagnosed with oesophageal adenocarcinoma is less than 20% [20]. For the purpose of this review, data were analyzed from the SEER 18 registries (covering approximately 28% of the United States’ population) to examine trends in relative survival rates for patients diagnosed with oesophageal cancer in the United States between 1973 and 2007 [21]. Since the early 1970s, there has been progressive improvement in overall 5-year

Demographics

The incidence of oesophageal adenocarcinoma increases with age and is rare among persons aged <50 years [22]. In the SEER 9 registries, for oesophageal adenocarcinoma diagnosed between 1973 and 2012, incidence rates were 21 times (RR, 20.8; 95% CI, 19.6–22.1) and 44 times (RR, 44.4; 95% CI, 41.8–47.1) higher among persons aged 50-69 years and ≥70 years, respectively, as that it was among persons aged <50 years (Table 1; Fig. 4). One of the most intriguing observations in oesophageal

Helicobacter pylori

H. pylori is a gram-negative bacterium that persistently colonizes the human stomach and causes gastric cancer [53]. In contrast, epidemiological studies have consistently observed an inverse association with oesophageal adenocarcinoma. Two recent meta-analyses both reported over 40% lower risk of oesophageal adenocarcinoma in persons infected with H. pylori [45], [46]. Epidemiological studies have not shown an association between H. pylori infection and oesophageal squamous-cell carcinoma [54]

Summary

The epidemiology of the two main subtypes of oesophageal cancer is very different. While the incidence of oesophageal adenocarcinoma continues to rise in the United States and other western populations, the incidence of oesophageal squamous-cell carcinoma continues to decline. The main risk factors for oesophageal adenocarcinoma are symptoms of gastro-oesophageal reflux disease, obesity and cigarette smoking (Table 2). Use of aspirin and nonsteroidal anti-inflammatory drugs and infection with

Conflicts of interest

I have no conflicts of interest.

Authorship contribution

APT performed all analyses and drafted the manuscript.

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