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

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; Weiguo HU

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

Author: Yuanyue ZHU ¹ ; Linhui SHEN ¹ ; Yanan HUO ² ; Qin WAN ³ ; Yingfen QIN ⁴ ; Ruying HU ⁵ ; Lixin SHI ⁶ ; Qing SU ⁷ ; Xuefeng YU ⁸ ; Li YAN ⁹ ; Guijun QIN ¹⁰ ; Xulei TANG ¹¹ ; Gang CHEN ¹² ; Yu XU ¹³ ; Tiange WANG ¹³ ; Zhiyun ZHAO ¹³ ; Zhengnan GAO ¹⁴ ; Guixia WANG ¹⁵ ; Feixia SHEN ¹⁶ ; Xuejiang GU ¹⁶ ; Zuojie LUO ⁴ ; Li CHEN ¹⁷ ; Qiang LI ¹⁸ ; Zhen YE ⁵ ; Yinfei ZHANG ¹⁹ ; Chao LIU ²⁰ ; Youmin WANG ²¹ ; Shengli WU ²² ; Tao YANG ²³ ; Huacong DENG ²⁴ ; Lulu CHEN ²⁵ ; Tianshu ZENG ²⁵ ; Jiajun ZHAO ²⁶ ; Yiming MU ²⁷ ; Weiqing WANG ¹³ ; Guang NING ¹³ ; Jieli LU ¹³ ; Min XU ²⁸ ; Yufang BI ²⁹ ; Weiguo HU ³⁰
Author Information

1. Department of Geriatrics, Medical Center on Aging, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
2. Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, 330006, China.
3. The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
4. The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
5. Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, China.
6. Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
7. Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
8. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
9. Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
10. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
11. The First Hospital of Lanzhou University, Lanzhou, 730000, China.
12. Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350003, China.
13. Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
14. Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian, 116033, China.
15. The First Hospital of Jilin University, Changchun, 130021, China.
16. The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
17. Qilu Hospital of Shandong University, Jinan, 250012, China.
18. The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
19. Central Hospital of Shanghai Jiading District, Shanghai, 201899, China.
20. Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, 210028, China.
21. The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
22. Karamay Municipal People's Hospital, Karamay, 834000, China.
23. The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
24. The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
25. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
26. Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250012, China.
27. Chinese People's Liberation Army General Hospital, Beijing, 100853, China.
28. Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. della.xumin@shsmu.edu.cn.
29. Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. byf10784@rjh.com.cn.
30. Department of Geriatrics, Medical Center on Aging, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. wghu@rjh.com.cn.
Publication Type:Observational Study
Keywords: Mendelian randomization; cancer risk; cholecystectomy; gallstone
MeSH: Humans; Mendelian Randomization Analysis; Gallstones/complications*; Female; Male; Cholecystectomy/statistics & numerical data*; Middle Aged; Risk Factors; Aged; Adult; Neoplasms/etiology*; Stomach Neoplasms/epidemiology*
From: Frontiers of Medicine 2025;19(1):79-89
CountryChina
Language:English
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.