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

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.