AccScience Publishing / JCTR / Online First / DOI: 10.36922/JCTR025260029
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ORIGINAL ARTICLE

Association between serum uric acid and prostate cancer risk: The modifying role of CTGF genotype

Randi Chen1* ,  Timothy A. Donlon1,2 ,  Richard C. Allsopp3 ,  Brian J. Morris1,4 ,  Bradley J. Willcox1,5 ,  Kamal H. Masaki1,5
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1 Department of Research, Kuakini Japan-Hawaii Cancer Study, Kuakini Honolulu Heart Program, Center of Biomedical Research Excellence (COBRE) for Clinical and Translational Research on Aging, Kuakini Medical Center, Honolulu, Hawaii, United States of America
2 Department of Cell and Molecular Biology, University of Hawaii, Honolulu, Hawaii, United States of America
3 Department of Anatomy, Biochemistry and Physiology, Institute for Biogenesis Research, University of Hawaii, Honolulu, Hawaii, United States of America
4 School of Medical Sciences, University of Sydney, Sydney, New South Wales, Australia
5 Department of Geriatric Medicine, University of Hawaii, Honolulu, Hawaii, United States of America
JCTR, 025260029 https://doi.org/10.36922/JCTR025260029
Received: 23 June 2025 | Revised: 16 September 2025 | Accepted: 30 September 2025 | Published online: 15 October 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Background: The role of uric acid in prostate cancer risk remains uncertain, with evidence suggesting both carcinogenic and protective effects. Genetic factors may be key modifiers of this association. Objective: This study aimed to determine whether the relationship between uric acid and prostate cancer risk differs by the rs9399005 genotype of connective tissue growth factor (CTGF). Methods: We examined 6,259 Japanese-American men in Hawaii, cancer-free at baseline (1965–1968, ages 45–68), who were followed for incident prostate cancer until 1999. Hyperuricemia was defined as serum uric acid ≥7.0 mg/dL. CTGF genotypes were classified as common allele homozygotes (CC) or minor allele carriers (T). Cox proportional hazards models estimated hazard ratios (HRs), adjusting for age and potential confounders. Results: During a median follow-up of 29.7 years, 285 prostate cancer cases were identified. A significant interaction between CTGF and hyperuricemia was observed. Among men with the CTGF–T genotype, hyperuricemia was not associated with risk (HR = 0.77, 95% confidence interval [CI]: 0.51–1.17). In contrast, among CTGF–CC homozygotes, hyperuricemia was linked to a higher risk (HR = 1.91, 95% CI: 1.21–2.99). Men with both the CTGF–CC genotype and hyperuricemia had a higher risk (HR = 1.72, 95% CI: 1.17–2.54) compared with all other subjects. Conclusion: The association between uric acid and prostate cancer varied by CTGF genotype. Hyperuricemia increased risk among CTGF–CC homozygotes, whereas a nonsignificant protective effect was seen among T allele carriers. Relevance to patients: Monitoring and lowering serum uric acid may help reduce prostate cancer risk in men with the CTGF–CC genotype.

Keywords
CTGF
Connective tissue growth factor
Uric acid
Hyperuricemia
Gene-environment interaction
Prostate cancer
Funding
This work was supported by NIH (Contract N01-AG-4-2149, Grants 5U01AG019349-05, 5R01AG027060 [Kuakini Hawaii Lifespan Study], 5R01AG038707 [Kuakini Hawaii Healthspan Study], and 1P20GM125526-01A1 [Kuakini HHP Center of Biomedical Research Excellence for Clinical and Translational Research on Aging]); the National Heart, Lung, and Blood Institute (Contract N01-HC-05102); and the National Cancer Institute (Contracts N01-CP-33216, N01-CN-55424, N01-CA-15655, and N01-CP61060 [Kuakini Japan-Hawaii Cancer Study]).
Conflict of interest
The authors declare that they have no competing interests.
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Journal of Clinical and Translational Research, Electronic ISSN: 2424-810X Print ISSN: 2382-6533, Published by AccScience Publishing
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