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Intra-individual variation in serum C-reactive protein over 4 years: an implication for epidemiologic studies

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Abstract

Background

Data on long-term intra-individual variability in high-sensitivity C-reactive protein (hsCRP) are needed to determine whether one measurement adequately reflects usual levels in prospective studies of on the etiology of cancer and other chronic diseases; when not reflective, the ability to statistically detect modest to moderate associations is reduced. The authors estimated the size of this source of variability and consequent attenuation of the relative risk (RR).

Methods

High-sensitivity C-reactive protein (hsCRP) concentration was measured using a high-sensitivity immunoturbidometric assay in sera collected at years 2, 4, and 6 from 50 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). After natural logarithm-transformation of hsCRP, analysis of variance was used to estimate the within- and between-individual variances from which the intra-class correlation coefficient (ICC) was calculated.

Results

The observed RR due to an ICC < 1 was calculated by e(ln true RR*ICC) for a range of true RRs. The 4-year ICC was 0.66. Measuring hsCRP once and assuming no other error, if the true RRs were 1.50, 2.00, and 3.00 when comparing high with low concentration, then the observed RRs would be 1.31, 1.58, and 2.06, respectively.

Conclusion

Investigators planning to measure hsCRP only once should design adequately sized studies to preserve inferences for hypothesized modest to moderate RRs.

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Acknowledgments

We thank Gary Bradwin at Children’s Hospital Boston, Bob Dayton at the University of Colorado, and Anna DeNooyer at the Johns Hopkins Bloomberg School of Public Health. This work was supported by the National Cancer Institute, National Institutes of Health (CCOP2016, P01 CA 108964). The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Rm E6132, Baltimore, MD, 21205, USA

    Elizabeth A. Platz

  2. James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Elizabeth A. Platz & Angelo M. De Marzo

  3. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Elizabeth A. Platz, Angelo M. De Marzo & Charles G. Drake

  4. Alvin J. Siteman Cancer Center and the Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA

    Siobhan Sutcliffe

  5. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Angelo M. De Marzo

  6. Department of Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Charles G. Drake

  7. Children’s Hospital Boston and the Harvard Medical School, Boston, MA, USA

    Nader Rifai

  8. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    Ann W. Hsing

  9. Department of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Ashraful Hoque

  10. Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Marian L. Neuhouser & Alan R. Kristal

  11. Southwest Oncology Group, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Phyllis J. Goodman

  12. Department of Epidemiology, University of Washington, Seattle, WA, USA

    Alan R. Kristal

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  1. Elizabeth A. Platz
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  2. Siobhan Sutcliffe
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  4. Charles G. Drake
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  7. Ashraful Hoque
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  8. Marian L. Neuhouser
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  9. Phyllis J. Goodman
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Corresponding author

Correspondence to Elizabeth A. Platz.

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Platz, E.A., Sutcliffe, S., De Marzo, A.M. et al. Intra-individual variation in serum C-reactive protein over 4 years: an implication for epidemiologic studies. Cancer Causes Control 21, 847–851 (2010). https://doi.org/10.1007/s10552-010-9511-z

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  • DOI: https://doi.org/10.1007/s10552-010-9511-z

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