Page 107 - JCTR-11-5

Journal of Clinical and
Translational Research Uric acid, CTGF genotype, and prostate cancer

Among men with the CTGF–CC genotype, were independently associated with prostate cancer
hyperuricemia was significantly associated with incidence. Next, we assessed whether the CTGF genotype
an increased risk of prostate cancer compared to modified the association between hyperuricemia and
normouricemic individuals (HR = 1.91, 95% CI: 1.21–2.99, prostate cancer by testing an interaction between the
p=0.005). Within this genotype group, only those in the CTGF genotype and hyperuricemia. We found no overall
highest serum uric acid quartile (Q4) had a significantly association between hyperuricemia and prostate cancer
elevated risk relative to Q1 (HR = 2.01, 95% CI: 1.16–3.50, incidence, consistent with previous studies using simple
p=0.014). In contrast, participants with the CTGF–T causeandeffect models. 12-15 The CTGF genotype alone
genotype showed nonsignificant inverse associations for likewise showed no independent effect on risk. However,
hyperuricemia (HR = 0.77, 95% CI: 0.51–1.17, p=0.22) and a significant interaction between CTGF genotype and
for Q4 versus Q1 (HR = 0.73, 95% CI: 0.45–1.18, p=0.20). hyperuricemia (p=0.010), estimated from the multivariate
“full model,” indicated that the impact of elevated uric acid
3.5. Relative risk (RR) of prostate cancer for on prostate cancer varies by CTGF2 genotype. Genotype-
exposure groups defined by the CTGF genotype and specific analyses revealed that among men homozygous for
hyperuricemia
the common allele (C), hyperuricemia was associated with
Figure 1 illustrates the adjusted RR of prostate cancer a 1.91fold increased prostate cancer risk compared to men
among four exposure groups defined by CTGF genotype with normouricemia. In contrast, among carriers of the
(CTGF–CC and CTGF–T) and hyperuricemia status. RRs minor allele (T), hyperuricemia exhibited a nonsignificant
were estimated using a multivariate Cox model adjusted inverse association. These findings underscore the
for potential confounders, with men carrying the CTGF–T importance of stratifying analyses by CTGF genotype in
genotype and normouricemia (normal) serving as the future studies of uric acid and prostate cancer to avoid
reference group. Notably, individuals with both the CTGF– obscuring associations within specific subpopulations.
CC genotype and hyperuricemia exhibited the highest
prostate cancer risk among all other exposure groups. Notably, neither hyperuricemia nor the CTGF–CC
Specifically, these individuals had a significantly increased genotype alone was associated with prostate cancer risk
risk (HR = 1.72, 95% CI: 1.17–2.54) compared to all other (Table 3). However, individuals with both hyperuricemia
subjects. and the CTGF–CC genotype exhibited an increased
risk (Figure 1). This finding aligns with one of the gene-
4. Discussion environment interaction scenarios described by Ottman,
28
where the simultaneous presence of a genetic variant
In this study, we first examined whether hyperuricemia and an environmental factor is required to raise disease
(defined as uric acid ≥7.0 mg/dL) and the CTGF genotype
susceptibility.
An earlier publication from our group indicated that
uric acid was associated with the risk of prostate cancer
during the first 10 years of follow-up, but not thereafter.
24
In contrast, the present study’s tests of the Cox proportional
hazards assumption for hyperuricemia, conducted within
each CTGF genotype, indicated that the HR for prostate
cancer associated with hyperuricemia remained constant
throughout the follow-up period.
Our findings have significant clinical relevance. We
recommend that clinicians consider genetic testing for
CTGF in men with hyperuricemia and provide personalized
recommendations to mitigate prostate cancer risk. For
instance, in men homozygous for the CTGF rs9399005
common allele (C), lifestyle modifications (such as reducing
Figure 1. Relative risk of prostate cancer for the exposure groups defined red meat and sugar consumption, quitting smoking,
by CTGF genotype and hyperuricemia status. The relative risks were
estimated from Cox models adjusted for age, BMI, smoking (pack-years), limiting alcohol intake, and increasing physical activity)
alcohol intake (oz/month), physical activity index, and percentage of should be strongly encouraged, alongside pharmacological
calories from animal protein; CTGF–T and normouricemia (Normal) interventions such as urate-lowering therapy.
were treated as the reference group.
Abbreviations: BMI: Body mass index; CTGF: Connective tissue growth Uric acid is known to exert both antioxidative and pro-
factor. inflammatory effects in cancer development. Based on our

Volume 11 Issue 5 (2025) 101 doi: 10.36922/JCTR025260029