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Genetically predicted serum urate and cancer risk : a Mendelian randomization study

Fatima, T. LU ; Dehlin, M. ; Burgess, S. ; Mason, A. M. LU ; Nilsson, P. M. LU ; Melander, O. LU orcid ; Jacobsson, L. T.H. LU and Kapetanovic, M. C. LU (2025) In Scandinavian Journal of Rheumatology 54(6). p.464-474
Abstract

Objective: To evaluate the causal effect of genetically predicted serum urate (SU) levels on the risk of overall and major site-specific cancers in individuals of European ancestry, using Mendelian randomization (MR) analysis. Method: Data from two population-based cohorts from southern Sweden, the Malmö Diet and Cancer Study (MDCS) and Malmö Preventive Project (MPP), and summary-statistics data from the Global Urate Genetic Consortium (GUGC) and UK Biobank cohort were used. A set of 26 SU-related variants was used as instrumental variables to perform a range of one- (using MDCS-MPP) and two-sample (using GUGC and UK Biobank) MR analyses. Causal relationships were assessed between genetically determined SU and 13 site-specific cancers... (More)

Objective: To evaluate the causal effect of genetically predicted serum urate (SU) levels on the risk of overall and major site-specific cancers in individuals of European ancestry, using Mendelian randomization (MR) analysis. Method: Data from two population-based cohorts from southern Sweden, the Malmö Diet and Cancer Study (MDCS) and Malmö Preventive Project (MPP), and summary-statistics data from the Global Urate Genetic Consortium (GUGC) and UK Biobank cohort were used. A set of 26 SU-related variants was used as instrumental variables to perform a range of one- (using MDCS-MPP) and two-sample (using GUGC and UK Biobank) MR analyses. Causal relationships were assessed between genetically determined SU and 13 site-specific cancers (bladder, breast, color ectal, gastric, hepatic, lung, pancreatic, prostate, renal, skin, lymphatic, haematopoietic, and gynaecological cancers, and brain tumour) and ‘any cancer’. We also performed epidemiological association analyses on individual-level data to determine SU–cancer relationships. Results: There was some suggestive evidence of an association between higher levels of genetically predicted SU and lower risk of brain (p = 0.04; one-sample MR) and colorectal (p = 0.02; two-sample MR) cancers, although these findings were not consistent across both MR approaches. No significant associations were observed between SU levels and the risk of other cancers (all p > 0.05). Conclusion: Our MR study found no consistent evidence of a causal effect of genetically predicted SU on overall or Q3 common site-specific cancers in European individuals.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scandinavian Journal of Rheumatology
volume
54
issue
6
pages
11 pages
publisher
Taylor & Francis
external identifiers
  • pmid:40583621
  • scopus:105009463627
ISSN
0300-9742
DOI
10.1080/03009742.2025.2512667
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
id
fc8bcef4-139d-4c11-b47f-eded8dde2213
date added to LUP
2026-01-12 16:14:59
date last changed
2026-01-13 03:04:09
@article{fc8bcef4-139d-4c11-b47f-eded8dde2213,
  abstract     = {{<p>Objective: To evaluate the causal effect of genetically predicted serum urate (SU) levels on the risk of overall and major site-specific cancers in individuals of European ancestry, using Mendelian randomization (MR) analysis. Method: Data from two population-based cohorts from southern Sweden, the Malmö Diet and Cancer Study (MDCS) and Malmö Preventive Project (MPP), and summary-statistics data from the Global Urate Genetic Consortium (GUGC) and UK Biobank cohort were used. A set of 26 SU-related variants was used as instrumental variables to perform a range of one- (using MDCS-MPP) and two-sample (using GUGC and UK Biobank) MR analyses. Causal relationships were assessed between genetically determined SU and 13 site-specific cancers (bladder, breast, color ectal, gastric, hepatic, lung, pancreatic, prostate, renal, skin, lymphatic, haematopoietic, and gynaecological cancers, and brain tumour) and ‘any cancer’. We also performed epidemiological association analyses on individual-level data to determine SU–cancer relationships. Results: There was some suggestive evidence of an association between higher levels of genetically predicted SU and lower risk of brain (p = 0.04; one-sample MR) and colorectal (p = 0.02; two-sample MR) cancers, although these findings were not consistent across both MR approaches. No significant associations were observed between SU levels and the risk of other cancers (all p &gt; 0.05). Conclusion: Our MR study found no consistent evidence of a causal effect of genetically predicted SU on overall or Q3 common site-specific cancers in European individuals.</p>}},
  author       = {{Fatima, T. and Dehlin, M. and Burgess, S. and Mason, A. M. and Nilsson, P. M. and Melander, O. and Jacobsson, L. T.H. and Kapetanovic, M. C.}},
  issn         = {{0300-9742}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{464--474}},
  publisher    = {{Taylor & Francis}},
  series       = {{Scandinavian Journal of Rheumatology}},
  title        = {{Genetically predicted serum urate and cancer risk : a Mendelian randomization study}},
  url          = {{http://dx.doi.org/10.1080/03009742.2025.2512667}},
  doi          = {{10.1080/03009742.2025.2512667}},
  volume       = {{54}},
  year         = {{2025}},
}