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Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well\u2010established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n\u2009=\u2009463\u2009643), Nurses' Health Study (NHS, n\u2009=\u200980\u2009235) and NHS II (n\u2009=\u200995\u2009869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow\u2010up: 7.6\u2009years), and 91 cases in NHS and NHS II cohorts (median follow\u2010up: 15.8\u2009years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44\u20102.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60\u20101.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60\u20101.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49\u20102.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52\u20102.27) and gallbladder cancers (HR 0.66, 95% CI 0.26\u20101.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.<\/jats:p>","DOI":"10.1002\/ijc.34572","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T07:44:05Z","timestamp":1685087045000},"page":"942-949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts"],"prefix":"10.1002","volume":"153","author":[{"given":"Qiangsheng","family":"He","sequence":"first","affiliation":[{"name":"Big Data Center, Scientific Research Center, The Seventh Affiliated Hospital Sun Yat\u2010sen University  Shenzhen Guangdong China"},{"name":"Clinical Research Center, The Seventh Affiliated Hospital Sun Yat\u2010sen University  Shenzhen Guangdong China"},{"name":"Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh 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