Strasak AM, Lang S, Kneib T, Brant LJ, Klenk J, Hilbe W, Oberaigner W, Ruttmann E, Kaltenbach L, Concin H, Diem G, Pfeiffer KP, Ulmer H
Use of Penalized Splines in Extended Cox-Type Additive Hazard Regression to Flexibly Estimate the Effect of Time-varying Serum Uric Acid on Risk of Cancer Incidence: A Prospective, Population-Based Study in 78,850 Men. [JOURNAL ARTICLE]
Ann Epidemiol 2008 Oct 2.
PURPOSE: We sough to investigate the effect of serum uric acid (SUA) levels on risk of cancer incidence in men and to flexibly determine the shape of this association by using a novel analytical approach.
METHODS: 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.
RESULTS: 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 (>/=8.00mg/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.
CONCLUSIONS: 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.
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