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Ann Epidemiol. 2009 Jan;19(1):15-24. doi: 10.1016/j.annepidem.2008.08.009. Epub 2008 Oct 4.

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.

Author information

1
Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Austria. alexander.strasak@i-med.ac.at

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.

PMID:
18835524
PMCID:
PMC2666912
DOI:
10.1016/j.annepidem.2008.08.009
[Indexed for MEDLINE]
Free PMC Article

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