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

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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