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We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50\u2009045 individuals using in\u2010person 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\u2009559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0\u2009years 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\u20101.24, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.013) as well as tobacco smoking (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.028) were observed. In post\u2010hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27\u20100.98 <jats:italic>P<\/jats:italic>\u00a0=\u00a0.04) and in smokers (aHR 0.26, 95% CI: 0.08\u20100.83 <jats:italic>P<\/jats:italic>\u00a0=\u00a0.02). 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.<\/jats:p>","DOI":"10.1002\/ijc.34313","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T15:37:58Z","timestamp":1665416278000},"page":"1137-1149","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Sex and smoking differences in the association between gastroesophageal reflux and risk of esophageal squamous cell carcinoma in a high\u2010incidence area: Golestan Cohort Study"],"prefix":"10.1002","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6900-5596","authenticated-orcid":false,"given":"Ali","family":"Soroush","sequence":"first","affiliation":[{"name":"Department of Medicine Columbia University Irving Medical Center  New York New York 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