Epidemiological studies on gastroesophageal reflux disease and esophageal cancer

Abstract: Esophageal cancer is the seventh most common cancer and a lethal malignancy causing a considerably high number of deaths around the world. Despite intensive studies on risk factors associated with esophageal cancer, there is currently no promising method for prevention, early detection, or screening of esophageal cancer. Consequently, most patients are diagnosed at an advanced stage, therefore associated with a poor prognosis. On the other hand, the main–stream treatment for esophageal cancer patients is surgery, which might be associated with complex complications or infections, and the 5–year postoperative survival remains low. Study I investigated sex disparities in postoperative survival after curative surgical treatment in esophageal cancer patients. A total of 1301 esophageal cancer patients who underwent curative surgery between 2006 and 2017 in Sweden were studied. Female patients showed a lower excess mortality rate than male patients, in both subtypes of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Moreover, the sex difference was more profound in those with early clinical stages, in patients who received neoadjuvant treatment, and without postoperative complications. Study II used data from the Barrett’s and Esophageal Adenocarcinoma Consortium to examine the association between 15 antibodies against Helicobacter pylori (H. pylori), gastric atrophy and EAC. Seropositivities of all the measured antibodies were associated with lower risks of EAC. Particularly, the inverse association between H. pylori and EAC was not mediated by gastric atrophy, body mass index (BMI), gastroesophageal reflux disease (GERD), or the combination of these factors. Study III explored the association between dental health, which was characterized by a group of dental diseases and remaining teeth number, and esophageal cancer. The study was carried out among 5 million individuals who visited the Swedish dental health care providers and received reimbursement between 2009 and 2016, in the Swedish Dental Health Register (DHR). Specifically, root canal infection at baseline was associated with 41% increased risk for EAC, while periodontitis was associated with an elevated risk for EAC and ESCC. Fewer remaining teeth at baseline was also observed to increase the risks for EAC and ESCC in a dose–response manner. Moreover, these findings were further corroborated when multiple visits during follow–up were included in the models. Study IV studied the association between atrophic gastritis (AG) and GERD in 12,533 twins. AG, which was measured by serum biomarkers, was shown to be associated with a reduced risk for the occurrence of symptomatic GERD. Additionally, the results were stable when different cut–off values were used to define the AG status. The results were also showed to be independent of familiar factors and genetic factors shared between twins. In conclusion, sex differentiated treatment should be considered to improve postoperative survival in esophageal cancer patients. H. pylori infection is associated with a reduced risk for EAC, dental health measured by specific diseases and remaining teeth number are potential predictive factors for esophageal cancer, and AG is associated with a lower risk for GERD, which is a risk factor for EAC. These studies shed light on etiological factors for esophageal cancer and GERD, and may help the prevention of the occurrence and improve the survival for esophageal cancer patients.