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Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts |
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| Authors: | Qiangsheng He Chongfei Huang Xiwen Qin Yuanyuan Yu Di Tang Junjie Huang Zi Chong Kuo Yuyao Ling Deli Mao Bin Xia Wenjing Li Kuiqing Lu Man Yang Yulong He Wenbo Meng Jinqiu Yuan Yihang Pan |
| Institution: | 1. Big Data Center, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China;2. Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China;3. Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Science, Monash University, Melbourne, Australia Victorian Heart Institute, Monash University, Melbourne, Australia Laboratory of Data Discovery for Health (D24H), The University of Hong Kong, Pokfulam, Hong Kong;4. Department of surgery, The Chinese University of Hong Kong, Shatin, Hong Kong;5. Department of surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China;6. JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong;7. Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China;8. School of Clinical Medicine, Sun Yat-sen University, Shenzhen, Guangdong, China;9. Big Data Center, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China;10. Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China;11. Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China;12. Big Data Center, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China |
| Abstract: | Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). 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-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes. |
| Keywords: | biliary tract cancer Nurses' Health Study proton pump inhibitor UK Biobank |