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

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.

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).

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.

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.

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.

Monitoring and lowering serum uric acid may help reduce prostate cancer risk in men with the CTGF-CC genotype.