Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study

Abstract

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50–4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17–5.16), kidney cancer (aOR=2.04, 95% CI 1.05–3.94), and bladder cancer (aOR=2.23, 95% CI 1.01–5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12–2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29–4.49), colorectal cancer (aOR=1.83, 95% CI 1.18–2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11–6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.

Keywords

gallstone / cholecystectomy / cancer risk / Mendelian randomization

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Acknowledgements

This work was funded by the National Natural Science Foundation of China (Nos. 82270859, 82370819, and 82088102), the National Key R&D Program of China (No. 2023YFC2506700), the Shanghai Municipal Government grant (No. 22Y31900300), and the Shanghai Clinical Research Center for Metabolic Diseases (No. 19MC1910100). The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-024-1111-5 and is accessible for authorized users.

Compliance with ethics guidelines

Conflicts of interest Yuanyue Zhu, Linhui Shen, Yanan Huo, Qin Wan, Yingfen Qin, Ruying Hu, Lixin Shi, Qing Su, Xuefeng Yu, Li Yan, Guijun Qin, Xulei Tang, Gang Chen, Yu Xu, Tiange Wang, Zhiyun Zhao, Zhengnan Gao, Guixia Wang, Feixia Shen, Xuejiang Gu, Zuojie Luo, Li Chen, Qiang Li, Zhen Ye, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Lulu Chen, Tianshu Zeng, Jiajun Zhao, Yiming Mu, Weiqing Wang, Guang Ning, Jieli Lu, Min Xu, Yufang Bi, and Weiguo Hu declare that they have no conflict of interest.

The study was approved by the Ethical Review Committee of Ruijin Hospital (No. RUIJIN-2011-14) and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all patients included in the study.

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