The causes of adenocarcinomas of the esophagus and gastric cardia are poorly understood. We conducted an epidemiologic investigation of the possible association between gastroesophageal reflux and these tumors.

The incidence of esophageal and gastric cardia adenocarcinoma is, for unknown reasons, increasing dramatically. A weak and inconsistent association between body mass index (BMI) and adenocarcinoma of the esophagus and gastric cardia has been reported. To reexamine the association between BMI and development of adenocarcinoma of the esophagus and gastric cardia. Nationwide, population-based case–control study. Sweden, 1995 through 1997. Patients younger than 80 years of age who had recently received a diagnosis were eligible. Comprehensive organization ensured rapid case ascertainment. Controls were randomly selected from the continuously updated population register. Interviews were conducted with 189 patients with adenocarcinoma of the esophagus and 262 patients with adenocarcinoma of the gastric cardia; for comparison, 167 patients with incident esophageal squamous-cell carcinoma and 820 controls were also interviewed. Odds ratios were determined from BMI and cancer case–control status. Odds ratios estimated the relative risk for the two adenocarcinomas studied and were calculated by multivariate logistic regression with adjustment for potential confounding factors. A strong dose-dependent relation existed between BMI and esophageal adenocarcinoma. The adjusted odds ratio was 7.6 (95% CI, 3.8 to 15.2) among persons in the highest BMI quartile compared with persons in the lowest. Obese persons (persons with a BMI > 30 kg/m²) had an odds ratio of 16.2 (CI, 6.3 to 41.4) compared with the leanest persons (persons with a BMI < 22 kg/m²). The odds ratio for patients with cardia adenocarcinoma was 2.3 (CI, 1.5 to 3.6) in those in the highest BMI quartile compared with those in the lowest BMI quartile and 4.3 (CI, 2.1 to 8.7) among obese persons. Esophageal squamous-cell carcinoma was not associated with BMI. The association between BMI and esophageal adenocarcinoma is strong and is not explained by bias or confounding. The carcinogenic mechanism, however, remains to be clarified. The increasing prevalence of obesity in western countries could be important in understanding the increasing occurrence of this tumor.

The incidence of esophageal adenocarcinoma (EAC) has increased in many Western countries and is higher in men than women. Some risk factors for EAC have been identified-mainly gastroesophageal reflux disease, Barrett's esophagus, obesity, and tobacco smoking. It is not clear whether interventions to address these factors can reduce risk of EAC, although some evidence exists for smoking cessation. Although consumption of alcohol is not associated with EAC risk, other exposures, such as physical activity, nutrition, and medication use, require further study. Genetic variants have been associated with risk for EAC, but their overall contribution is low. Studies are needed to investigate associations between risk factors and the molecular subtypes of EAC. The prognosis for patients with EAC has slightly improved, but remains poor-screening and surveillance trials of high-risk individuals are needed.

Quiz Ref ID Gastroesophageal reflux disease (GERD) is defined by its cardinal symptoms (recurrent and troublesome heartburn and regurgitation) or by its specific complications (esophagitis, peptic strictures, and Barrett esophagus).¹ Barrett esophagus is a columnar metaplasia replacing parts of the native squamous cell epithelium that can progress to esophageal adenocarcinoma.² GERD can be a serious problem and should not be confused with less severe disease such as gastritis or the very common symptoms of dyspepsia or regurgitation that occur in almost all individuals without any underlying gastrointestinal pathology. GERD is caused by gastric contents’ reaching the esophagus. Except for causing esophageal symptoms or complications, gastric juices can also reach more proximally (ie, into the pharynx, mouth, larynx, and airways) and cause or worsen various extraesophageal symptoms and conditions such as hoarseness, wheezing, cough, and asthma.¹ Quiz Ref ID Established risk factors for developing GERD include increased body mass index, tobacco smoking, and genetic predisposition,³ whereas infection with the gastric bacterium Helicobacter pylori can decrease this risk.⁴ The prevalence of GERD is high and increasing, with greater rates in high-income countries (15%-25%) than in most low- and middle-income countries (<10%).^2,5 GERD can result in diminished health-related quality of life, and its prevalence and need for long-term treatment can consume substantial health care resources and result in high costs to society.^6,7 This review provides an update of the current evidence regarding GERD, with an emphasis on its clinical management in adults.

Gastroesophageal reflux disease and obesity are both highly prevalent in Western societies, and the occurrence of these conditions is rapidly increasing.^1-7 Reflux has an adverse impact on quality of life,⁸ and the costs for long-term antireflux medication are high.⁹ Reflux symptoms^10-12 and obesity^13,14 are strong and independent risk factors for esophageal adenocarcinoma, a cancer that has increased significantly in incidence during recent decades.^15,16