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Epidemiology

Gallstones and risk of cancers of the liver, biliary tract and pancreas: a prospective study within two U.S. cohorts

British Journal of Cancer volume 127, pages 1069–1075 (2022)Cite this article

Subjects

Abstract

Background

Gallstones may result in inflammation, altered bile flow, and changes in metabolic hormone levels, thereby increasing cancer risk. However, previous studies for gallstones and cancers of the liver, biliary tract and pancreas in the U.S. were relatively limited.

Methods

We followed 115,036 women from the Nurses’ Health Study (1982–2012) and 49,729 men from the Health Professionals Follow-up Study (1986–2012). History of gallstones, including with or without performed cholecystectomy, was reported at baseline and updated through biennial questionnaires. The Cox proportional hazard regression model was used to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results

During up to 30-year follow-up, we identified 204 incidents of liver cancer, 225 biliary tract cancer and 1147 pancreatic cancer cases. Compared to those without gallstones diagnosis, the multivariable HRs for individuals with gallstones (untreated or with cholecystectomy) were 1.60 for liver cancer (95% CI: 1.14–2.26), 4.79 for biliary tract cancer (95% CI: 3.02–7.58), and 1.13 for pancreatic cancer (95% CI: 0.96–1.32). The multivariable HRs for individuals with cholecystectomy were 1.33 for liver cancer (95% CI: 0.90–1.95) and 1.15 for pancreatic cancer (95% CI: 0.98–1.36).

Conclusions

Gallstones were associated with a higher risk of cancers of the liver, biliary tract and possibly pancreas.

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Data availability

Restrictions apply to the availability of these data, which were used under license for this study. Data are available [https://sites.google.com/channing.harvard.edu/cohortdocs/] with the permission of BWH and Harvard T.H. Chan School of Public Health.

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Acknowledgements

We would like to thank the participants and staff of the NHS and the HPFS for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA and WY. The authors assume full responsibility for the analyses and interpretation of these data.

Funding

The HPFS and NHS were supported by the NCI at the NIH (grant numbers UM1 CA186107, P50 CA127003, P01 CA87969 and U01 CA167552). This work was supported by NIH grants (K07 CA188126 to XZ, and R21 CA238651 to XZ). XZ is also supported by the American Cancer Society Research Scholar Grant (RSG NEC-130476), NIH/NCI The Method to Extend Research in Time MERIT Award (R37 CA262299), Dana-Farber Harvard Cancer Center (DF/HCC), as well as Zhu Family Center at Harvard T.H. Chan School of Public Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Xiao Luo, Kana Wu, Xing Liu, Edward L. Giovannucci & Xuehong Zhang

  2. Department of Health Statistics, School of Public Health, China Medical University, Shenyang, Liaoning, P. R. China

    Xiao Luo

  3. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Wanshui Yang, Amit D. Joshi, Lina Jin, Lu Long, Andrew T. Chan, Edward L. Giovannucci & Xuehong Zhang

  4. School of Public Health, Anhui Medical University, Hefei, Anhui, P. R. China

    Wanshui Yang

  5. Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Tracey G. Simon

  6. Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Tracey G. Simon, Chun-Han Lo & Andrew T. Chan

  7. Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA

    Tracey G. Simon, Chun-Han Lo & Andrew T. Chan

  8. Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA

    Chen Yuan & Brian M. Wolpin

  9. Department of Epidemiology and Biostatistics, Jilin University School of Public Health, Changchun, Jilin, P. R. China

    Lina Jin

  10. Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Sichuan, P. R. China

    Lu Long

  11. Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea

    Mi Na Kim

  12. Laboratory of Clinical Epidemiology in Hepatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea

    Mi Na Kim

  13. Department of Epidemiology, School of Public Health, Fudan University, Shanghai, P. R. China

    Xing Liu

  14. Dana-Farber Cancer Institute, Boston, MA, USA

    Thomas A. Abrams

  15. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Edward L. Giovannucci

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  1. Xiao Luo
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  16. Xuehong Zhang
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Contributions

Drs. Luo and Zhang had full access to all the data in the study and took. responsibility for the integrity of the data and the accuracy of the data analysis. Acquisition of the data: KW, BMW, ATC, ELG and XZ. Analysis and interpretation of the data: XL. Drafting of the manuscript: XL. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: XL. Obtained funding: ELG and XZ. Administrative, technical or material support: KW, BMW, ATC, ELG and XZ. Study supervision: ELG and XZ.

Corresponding author

Correspondence to Xuehong Zhang.

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This study was approved by the Institutional Review Boards of the Brigham and Women’s Hospital and the Harvard T.H. Chan School of Public Health and of participating registries as required. Completion of the questionnaire was considered to imply informed consent.

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Luo, X., Yang, W., Joshi, A.D. et al. Gallstones and risk of cancers of the liver, biliary tract and pancreas: a prospective study within two U.S. cohorts. Br J Cancer 127, 1069–1075 (2022). https://doi.org/10.1038/s41416-022-01877-5

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