Dr. Bill Grady and colleagues review the status of chemopreventatives for progression of Barrett's to esophageal adenocarcinoma
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.
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
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
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/].