Literature DB >> 18835524

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.

Alexander M Strasak1, Stefan Lang, Thomas Kneib, Larry J Brant, Jochen Klenk, Wolfgang Hilbe, Willi Oberaigner, Elfriede Ruttmann, Lalit Kaltenbach, Hans Concin, Günter Diem, Karl P Pfeiffer, Hanno Ulmer.   

Abstract

PURPOSE: We sought 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 (>/=8.00 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.
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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Year:  2008        PMID: 18835524      PMCID: PMC2666912          DOI: 10.1016/j.annepidem.2008.08.009

Source DB:  PubMed          Journal:  Ann Epidemiol        ISSN: 1047-2797            Impact factor:   3.797


  33 in total

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