Sex and smoking differences in the association between gastroesophageal reflux and risk of esophageal squamous cell carcinoma in a high‐incidence area: Golestan Cohort Study

Abstract

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in‐person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66‐1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post‐hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27‐0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08‐0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.

Current Status and Future Prospects for Esophageal Cancer

“…Although GERD was not previously recognized as a risk factor for ESCC [48], a prospective cohort study of almost 500,000 participants in the United States showed a two-fold increased ESCC risk among individuals with GERD during a 16-year follow-up period [122]. However, another prospective cohort study of 50,000 participants in a highrisk region of Iran showed no increase in ESCC risk among individuals with GERD during a 13-year follow-up period [123].…”

Spatiotemporal Patterns of Esophageal Cancer Burden Attributable to Behavioral, Metabolic, and Dietary Risk Factors From 1990 to 2019: Longitudinal Observational Study

“…There was a significant male predominance in EC cases with a male-to-female incidence ratio of 3.3:1 for ESCC and 6.7:1 for EAC [ 8 ]. Further, the interaction effect of sex and smoking in ESCC has been reported in a cohort study with 13 years of median follow-up [ 12 ]. However, comprehensive understanding of EC risk–attributable burden does not exist in many countries, leading to a void in the up-to-date prevention strategies and adjustment in the EC treatment research focus.…”