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Genetic evidence for associations between gastroesophageal reflux disease and site-specific extraesophageal cancers: A Mendelian randomization study.

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Τίτλος: Genetic evidence for associations between gastroesophageal reflux disease and site-specific extraesophageal cancers: A Mendelian randomization study.
Συγγραφείς: Wang S; Department of Oncology, Sichuan University West China Hospital Guang'an Hospital, Guang'an, Sichuan, China., Guo M; Department of Oncology, Sichuan University West China Hospital Jin Cheng Hospital, Chengdu, Sichuan, China., Zhang S; Department of Oncology, Sichuan Provincial People's Hospital Jin Niu Hospital, Chengdu, Sichuan, China., Long X; Department of Oncology, Sichuan University West China Hospital Guang'an Hospital, Guang'an, Sichuan, China., He J; Department of Oncology, Sichuan University West China Hospital Guang'an Hospital, Guang'an, Sichuan, China.
Πηγή: Medicine [Medicine (Baltimore)] 2026 Oct 02; Vol. 105 (40), pp. e50874.
Τύπος έκδοσης: Journal Article; Meta-Analysis
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 2985248R Publication Model: Print Cited Medium: Internet ISSN: 1536-5964 (Electronic) Linking ISSN: 00257974 NLM ISO Abbreviation: Medicine (Baltimore) Subsets: MEDLINE
Imprint Name(s): Original Publication: Hagerstown, Md : Lippincott Williams & Wilkins
Ιατρικοί όροι (MeSH): Gastroesophageal Reflux*/genetics , Gastroesophageal Reflux*/complications , Mendelian Randomization Analysis*, Lung Neoplasms/genetics ; Pancreatic Neoplasms/genetics ; Humans ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Risk Factors ; Polymorphism, Single Nucleotide
Περίληψη: Observational studies have suggested an increased risk of extraesophageal cancers in patients with gastroesophageal reflux disease (GERD), but whether these associations are causal remains uncertain. This study systematically evaluated the potential associations between genetically predicted GERD and 22 extraesophageal cancers. Genetic instruments for GERD were obtained from a large genome-wide association study including 129,080 cases and 473,524 controls. Outcome data for 22 site-specific extraesophageal cancers were obtained from multiple genome-wide association study datasets, including the UK Biobank, FinnGen, and international cancer consortia. Two-sample Mendelian randomization (MR) analyses were performed, and dataset-specific MR estimates were subsequently combined using meta-analysis. For positive findings, reverse MR and Multivariable Mendelian randomization analyses were further conducted to assess causal direction and independence from body mass index, smoking intensity, and alcohol consumption. Meta-analysis of two-sample MR showed Bonferroni-significant positive associations of genetically predicted GERD with lung cancer (odds ratio [OR] = 1.220; 95% confidence interval [CI]: 1.100-1.354; P = .0002) and pancreatic cancer (OR = 1.517; 95% CI: 1.214-1.895; P = .0002). Suggestive positive associations were also observed for laryngeal cancer (OR = 1.774; 95% CI: 1.091-2.884; P = .021) and bladder cancer (OR = 1.254; 95% CI: 1.047-1.501; P = .014), although neither survived Bonferroni correction. In Multivariable Mendelian randomization analyses accounting for body mass index, smoking intensity, and alcohol consumption, the association with lung cancer remained statistically significant (OR = 1.190; 95% CI: 1.040-1.362; P = .012), whereas the associations with pancreatic, laryngeal, and bladder cancers were no longer statistically significant. These findings provide genetic evidence supporting an association between genetically predicted GERD and lung cancer. The evidence for pancreatic, laryngeal, and bladder cancers was less robust and requires further validation in larger independent datasets. These findings may help prioritize future research on cancer risk among individuals with GERD, with further studies warranted to validate the observed associations and clarify their underlying mechanisms.
(Copyright © 2026 the Author(s). Published by Wolters Kluwer Health, LLC.)
Competing Interests: The authors have no funding and conflicts of interest to declare.
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Contributed Indexing: Keywords: Mendelian randomization; gastroesophageal reflux disease; lung cancer; pancreatic cancer
Entry Date(s): Date Created: 20261002 Date Completed: 20261002 Latest Revision: 20261005
Update Code: 20261006
PubMed Central ID: PMC13632957
DOI: 10.1097/MD.0000000000050874
PMID: 42826299
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1536-5964
DOI:10.1097/MD.0000000000050874