A population-based cohort of 78,850 Austrian men who received 264,347 serial SUA measurements was prospectively followed-up for a median of 12.4 years. Data were collected between 1985 and 2003. Penalized splines (P-splines) in extended Cox-type additive hazard regression were used to flexibly model the association between SUA, as a time-dependent covariate, and risk of overall and site-specific cancer incidence and to calculate adjusted hazard ratios with their 95 % confidence intervals.
During follow-up 5189 incident cancers were observed. Restricted maximum-likelihood optimizing P-spline models revealed a moderately J-shaped effect of SUA on risk of overall cancer incidence, with statistically significantly increased hazard ratios in the upper third of the SUA distribution. Increased SUA (≥8.00 mg/dL) further significantly increased risk for several site-specific malignancies, with P-spline analyses providing detailed insight about the shape of the association with these outcomes.
Our study is the first to demonstrate a dose–response association between SUA and cancer incidence in men, simultaneously reporting on the usefulness of a novel methodological framework in epidemiologic research.