Background

The esophagus (blue in figure) is a muscular tube that carries food  from the back of the mouth (pharynx – green) to the stomach (red).  Cancers that occur in this organ are often difficult to treat, in part  because “alarm symptoms” such as difficulty swallowing (dysphagia) or  bleeding often do not appear until the cancer is at a late stage.  Unfortunately, only about half of persons with esophageal cancer survive  more than a year after diagnosis. Therefore, preventing the  cancer and detecting it at an early stage remain the most effective  options for reducing mortality from the disease.

Two histologic types of cancer typically occur in the esophagus. It  is normally lined by squamous cells, which can give rise to a type of  cancer – esophageal squamous cell carcinoma (ESCC) –  occurring anywhere in the esophagus. Sometimes the squamous cell lining  can be transformed into columnar cells which are similar to the lining  of the small intestine, in a process termed metaplasia. This usually  occurs under conditions of chronic gastroesophageal reflux (e.g.,  heartburn or acid regurgitation) and the resulting condition is termed Barrett’s esophagus. A second type of cancer – esophageal adenocarcinoma (EAC)  – typically arises in Barrett’s epithelium and usually develops within  the lower one-third of the esophagus or at the junction with the stomach  (gastroesophageal junction.) For the time being, this resource will  focus on EAC, which is the most common type of esophageal cancer in the  U.S. As resources permit, it will be expanded to include ESCC, which is  the most common type worldwide.

Figure 1.

In 2018, it is estimated that more than 550,000 new cases of  esophageal  cancer (both types) will have occurred worldwide, making it the seventh most commonly occurring cancer and the sixth most common cause of cancer  death.1

In lower income regions, squamous cell carcinoma is by far the most common histological type. Particularly high rates occur in parts of China, Central Asia and Eastern Africa (figure 1.) In contrast, the United States and much of Western Europe and Australia has seen a remarkable rise in the incidence of esophageal adenocarcinoma (EAC)  which has transformed it from a relative rarity in the 1970s to the most common histological type of esophageal cancer in the U.S. today.2–5

Figure 2. EAC incindence in white males in U.S. 

EAC is most common among white males, in whom incidence has  increased about 10-fold in the U.S. since the early 1970s (figure 2.)6  Incidence rates in other groups also have risen, although from a much lower baseline rate. Like many solid tumors, EAC incidence rises rapidly with age (figure 3, left graph.) Persons diagnosed with  Barrett’s  esophagus are substantially more likely (about 20-fold at 60  years of  age) to develop EAC than the general population (figure 3,  right graph.)7

Figure 3. Incidence of EAC in U.S. In the general population (left graph) EAC is much more common among white males at all ages. Persons with Barrett’s esophagus (right graph) are at substantially higher risk of developing EAC (note the very different scales) than in the general population.7

References:

1. Cancer today. Available at: http://gco.iarc.fr/today/home. (Accessed: 19th November 2018)

2. Hur, C. et al. Trends in esophageal adenocarcinoma incidence and mortality. Cancer119, 1149–58 (2013).

3. Islami, F., DeSantis, C. E.  & Jemal, A. Incidence Trends of Esophageal and Gastric Cancer  Subtypes by Race, Ethnicity, and Age in the United States, 1997-2014. Clin. Gastroenterol. Hepatol. (2018). doi:10.1016/j.cgh.2018.05.044

4. Malhotra, G. K. et al. Global trends in esophageal cancer. J. Surg. Oncol. 115, 564–579 (2017).

5. Xie, S.-H. & Lagergren, J. Risk factors for oesophageal cancer. Best Pract. Res. Clin. Gastroenterol. (2018). doi:10.1016/j.bpg.2018.11.008

6. Vaughan, T. L. & Fitzgerald, R. C. Precision prevention of oesophageal adenocarcinoma. Nat. Rev. Gastroenterol. Hepatol. 12, 243–248 (2015).

7. Anon. IC-RISC. Available at: [https://ic-risc.fredhutch.org/].