Objective: To measure the extent to which risks of oesophageal cancers associated with gastro-oesophageal reflux (GOR) are modified by common factors including smoking, non-steroidal anti-inflammatory drugs (NSAIDs) and acid suppressant medications.
Design and setting: Population-based case–control study.
Participants: Cases were patients with oesophageal (OAC; n = 365) or gastro-oesophageal junction (GOJAC; n = 426) adenocarcinomas, or squamous cell carcinomas (OSCC; n = 303). Controls were sampled from a population register (n = 1580).
Main outcome measure: Odds ratio and 95% confidence interval.
Results: Frequent (at least weekly) symptoms of GOR were associated with significant 6.4-fold, 4.6-fold and 2.2-fold increased risks of OAC, GOJAC and OSCC, respectively. Under models examining effects of combined exposure, patients with frequent GOR symptoms who were also heavy smokers had markedly higher OAC risks (OR = 12.3, 95% CI 6.3 to 24.0) than those with frequent GOR who did not smoke (OR = 6.8, 95% CI 3.6 to 12.9). Similar patterns were observed for GOJAC and OSCC. Among people with frequent GOR symptoms, regular use of aspirin/NSAIDs was associated with almost two-thirds lower OAC risks (OR = 4.8, 95% CI 2.5 to 9.2) than non-users (13.9, 95% CI 6.5 to 30.0). In contrast, among those with frequent GOR symptoms, users of acid suppressants had similar OAC risks (OR 7.8, 95% CI 5.2 to 11.8) to non-users (OR 5.3, 95% CI 3.2 to 9.0).
Conclusions: People experiencing frequent GOR symptoms have markedly increased risks of OAC and GOJAC, and this effect may be greater amongst smokers. Use of aspirin and NSAIDs, but not acid suppressants, significantly reduced the risks of oesophageal cancers associated with GOR.
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Funding This study was supported by the Queensland Cancer Fund and the National Health and Medical Research Council (NHMRC) of Australia (Program no. 199600). DW and PW are supported by Research Fellowships from the NHMRC. NP and SS were supported by PhD scholarships from the NHMRC and the Ministry of Health and Medical Education of the Islamic Republic of Iran, respectively. The funding bodies played no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.
Competing interests None.
Ethics approval This study was approved by the Human Research Ethics Committee of the Queensland Institute of Medical Research (Project-ID P399) and all participants gave their written consent to participate.
Authors’ contributions: NP performed the statistical analysis and prepared the manuscript. SS assisted in data preparation and interpretation. DW, PW and AG designed the original study and supervised the collection of data. All authors assisted in preparing the manuscript and approved the final version.
Provenance and Peer review Not commissioned; externally peer reviewed.