Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Gallstones, Cholecystectomy, and Kidney Cancer : Observational and Mendelian Randomization Results Based on Large Cohorts

Kharazmi, Elham LU ; Scherer, Dominique ; Boekstegers, Felix ; Liang, Qunfeng LU ; Sundquist, Kristina LU ; Sundquist, Jan LU ; Fallah, Mahdi LU and Bermejo, Justo Lorenzo (2023) In Gastroenterology 165(1). p.8-227
Abstract

BACKGROUND & AIMS: Gallstones (cholelithiasis) constitute a major health burden with high costs related to surgical removal of the gallbladder (cholecystectomy), generally indicated for symptomatic gallstones. The association between gallstones and cholecystectomy and kidney cancer is controversial. We comprehensively investigated this association, considering age at cholecystectomy and time from cholecystectomy to kidney cancer diagnosis, and assessed the causal effect of gallstones on kidney cancer risk by Mendelian randomization (MR).

METHODS: We compared the risk of kidney cancer in cholecystectomized and noncholecystectomized patients (16.6 million in total) from the Swedish nationwide cancer, census, patient, and death... (More)

BACKGROUND & AIMS: Gallstones (cholelithiasis) constitute a major health burden with high costs related to surgical removal of the gallbladder (cholecystectomy), generally indicated for symptomatic gallstones. The association between gallstones and cholecystectomy and kidney cancer is controversial. We comprehensively investigated this association, considering age at cholecystectomy and time from cholecystectomy to kidney cancer diagnosis, and assessed the causal effect of gallstones on kidney cancer risk by Mendelian randomization (MR).

METHODS: We compared the risk of kidney cancer in cholecystectomized and noncholecystectomized patients (16.6 million in total) from the Swedish nationwide cancer, census, patient, and death registries using hazard ratios (HRs). For 2-sample and multivariable MR, we used summary statistics based on 408,567 UK Biobank participants.

RESULTS: During a median follow-up of 13 years, 2627 of 627,870 cholecystectomized Swedish patients developed kidney cancer (HR, 1.17; 95% CI, 1.12-1.22). Kidney cancer risk was particularly increased in the first 6 months after cholecystectomy (HR, 3.79; 95% CI, 3.18-4.52) and in patients cholecystectomized before age 40 years (HR, 1.55; 95% CI, 1.39-1.72). MR results based on 18,417 patients with gallstones and 1788 patients with kidney cancer from the United Kingdom revealed a causal effect of gallstones on kidney cancer risk (9.6% risk increase per doubling in gallstone prevalence; 95% CI, 1.2%-18.8%).

CONCLUSIONS: Both observational and causal MR estimates based on large prospective cohorts support an increased risk of kidney cancer in patients with gallstones. Our findings provide solid evidence for the compelling need to diagnostically rule out kidney cancer before and during gallbladder removal, to prioritize kidney cancer screening in patients undergoing cholecystectomy and aged 30-39 years, and to investigate the underlying mechanisms linking gallstones and kidney cancer in future studies.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Gastroenterology
volume
165
issue
1
pages
18 pages
publisher
Elsevier
external identifiers
  • pmid:37054756
  • scopus:85161477025
ISSN
1528-0012
DOI
10.1053/j.gastro.2023.03.227
language
English
LU publication?
yes
additional info
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
id
46d383aa-8120-48bc-b1fc-8c65d73fd5a8
date added to LUP
2023-05-05 13:00:21
date last changed
2024-06-16 05:19:50
@article{46d383aa-8120-48bc-b1fc-8c65d73fd5a8,
  abstract     = {{<p>BACKGROUND &amp; AIMS: Gallstones (cholelithiasis) constitute a major health burden with high costs related to surgical removal of the gallbladder (cholecystectomy), generally indicated for symptomatic gallstones. The association between gallstones and cholecystectomy and kidney cancer is controversial. We comprehensively investigated this association, considering age at cholecystectomy and time from cholecystectomy to kidney cancer diagnosis, and assessed the causal effect of gallstones on kidney cancer risk by Mendelian randomization (MR).</p><p>METHODS: We compared the risk of kidney cancer in cholecystectomized and noncholecystectomized patients (16.6 million in total) from the Swedish nationwide cancer, census, patient, and death registries using hazard ratios (HRs). For 2-sample and multivariable MR, we used summary statistics based on 408,567 UK Biobank participants.</p><p>RESULTS: During a median follow-up of 13 years, 2627 of 627,870 cholecystectomized Swedish patients developed kidney cancer (HR, 1.17; 95% CI, 1.12-1.22). Kidney cancer risk was particularly increased in the first 6 months after cholecystectomy (HR, 3.79; 95% CI, 3.18-4.52) and in patients cholecystectomized before age 40 years (HR, 1.55; 95% CI, 1.39-1.72). MR results based on 18,417 patients with gallstones and 1788 patients with kidney cancer from the United Kingdom revealed a causal effect of gallstones on kidney cancer risk (9.6% risk increase per doubling in gallstone prevalence; 95% CI, 1.2%-18.8%).</p><p>CONCLUSIONS: Both observational and causal MR estimates based on large prospective cohorts support an increased risk of kidney cancer in patients with gallstones. Our findings provide solid evidence for the compelling need to diagnostically rule out kidney cancer before and during gallbladder removal, to prioritize kidney cancer screening in patients undergoing cholecystectomy and aged 30-39 years, and to investigate the underlying mechanisms linking gallstones and kidney cancer in future studies.</p>}},
  author       = {{Kharazmi, Elham and Scherer, Dominique and Boekstegers, Felix and Liang, Qunfeng and Sundquist, Kristina and Sundquist, Jan and Fallah, Mahdi and Bermejo, Justo Lorenzo}},
  issn         = {{1528-0012}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{1}},
  pages        = {{8--227}},
  publisher    = {{Elsevier}},
  series       = {{Gastroenterology}},
  title        = {{Gallstones, Cholecystectomy, and Kidney Cancer : Observational and Mendelian Randomization Results Based on Large Cohorts}},
  url          = {{http://dx.doi.org/10.1053/j.gastro.2023.03.227}},
  doi          = {{10.1053/j.gastro.2023.03.227}},
  volume       = {{165}},
  year         = {{2023}},
}