Medication Use and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus

Esophageal adenocarcinoma has increased sharply in incidence in the United States and western Europe over the past few decades. In contrast, the incidence rate for esophageal squamous cell carcinoma which, prior to the 1990s, accounted for the majority of esophageal cancers, has remained stable or decreased during that time. The incidence rate of esophageal adenocarcinoma differs by race and gender. Among white males, the incidence has increased more than 350% since the mid-1970s. Incidence has increased among black males, but much less markedly and the rate remains at approximately one-fifth the level of white males. Incidence of this cancer has increased to a similar extent among females, but the rate remains much lower than for males.

The rapid increase in the incidence of this cancer among some populations suggests an increase in the prevalence of some risk factors in recent decades. While certain risk factors have been identified, much of the increasing trend remains unexplained. Although still relatively uncommon, the poor prognosis for esophageal adenocarcinoma lends urgency to efforts to identify risk factors.

A large proportion of esophageal adenocarcinomas occur in persons with a history of gastroesophageal reflux. This acid reflux is believed to cause metaplasia of the esophagus, a condition known as Barrett's esophagus, which can lead to adenocarcinoma. Several common medications can increase gastroesophageal reflux by reducing pressure in the lower esophageal sphincter (LES) or by impairing esophageal motility. These medications may be contributing to the increasing incidence of esophageal adenocarcinoma through their effects on LES pressure or esophageal motility and their rising prevalence of use.

The overall objective of this epidemiologic study is to determine whether certain prescribed medications are risk factors for esophageal adenocarcinoma or Barrett's esophagus. The specific aims are to examine:

1. The risks of esophageal adenocarcinoma and Barrett's esophagus in relation to the use of medications that relax the lower esophageal sphincter (LES).
2. The associations of esophageal adenocarcinoma and Barrett's esophagus with the use of prescription non-steroidal anti-inflammatory drugs, which may be protective for these diseases.
3. The associations between esophageal adenocarcinoma and certain medical conditions such as Barrett's esophagus and gastroesophageal reflux disease (GERD).

This is the Pilot Phase of a planned two-phase case-control study involving two CRN health plan members, Group Health Cooperative and Henry Ford Health System. In Phase I, computerized records were used to identify persons diagnosed with either esophageal cancer or Barrett's esophagus. These cases will be compared to controls on the use of certain categories of medication as well as individual medications within those categories. Computerized pharmacy records will be utilized to examine not only of whether a subject used a given medication, but also the prescribed dose, frequency of prescription refills, and duration of use. Esophageal adenocarcinoma cases will also be compared to controls for a history of selected medical conditions, including Barrett's esophagus. Although Phase I will rely primarily on computerized records for data acquisition, a medical chart abstraction form will also be developed and pilot tested to help evaluate the availability from medical records of information on potential co-variates and confounding variables.

Project Status: This pilot study was funded in September 2002 through a 1-year contract with the NCI. The principal investigator is Larry Engel, PhD, from Memorial Sloan-Kettering Cancer Center. Dr. Engel was previously a scientist in the National Cancer Institute's Division of Cancer Epidemiology and Genetics.

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