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Serum cholesterol trajectories in the 10 years prior to lymphoma diagnosis

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Abstract

Purpose

Many studies suggest a role for cholesterol in cancer development. Serum cholesterol levels have been observed to be low in newly diagnosed lymphoma cases. The objective of these analyses was to examine the time-varying relationship of cholesterol with lymphomagenesis in the 10 years prior to diagnosis by lymphoma subtype.

Methods

Participants were selected from the combined membership of six National Cancer Institute-funded Cancer Research Network health plans from 1998 to 2008, excluding members with human immunodeficiency virus, cancer (except lymphoma), or organ transplants. Incident lymphoma cases within this population were ascertained and matched with up to five controls. Total serum cholesterol, high-density lipoprotein, and low-density lipoprotein were collected from plan databases. Multilevel, multivariable longitudinal models were fit after choosing the best polynomial order by deviance statistics for selected lymphoma histotypes to examine pre-diagnosis cholesterol trajectories: Hodgkin lymphoma (n = 519) and all non-Hodgkin lymphomas combined (n = 12,635) as well as six subtypes of the latter.

Results

For all categories, lymphoma cases had statistically significantly lower estimated total serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels than controls in the years prior to diagnosis/index date. Between-group differences were most pronounced 3–4 years prior to diagnosis, when cases’ cholesterol levels declined steeply.

Conclusions

This analysis is the first to examine changes in serum cholesterol for a decade prior to lymphoma diagnosis. A drop in cholesterol levels was evident several years before diagnosis. Our results suggest that cholesterol-related pathways have an important relationship with lymphomagenesis and low cholesterol could be a preclinical lymphoma marker.

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Acknowledgments

This work was funded by the USA NIH National Cancer Institute, R01 CA140754. Additional Members of the Cancer Research Network Lymphoma Study Group: Ninah Achacoso, Denise Boudreau, Lie Chen, Melody Eide, James Fraser, Gene Hart, Jill Koshiol, Melissa Preciado, Junling Ren, Zaineb Sharafali, Leslie Spangler, David Tabano, Noah Weston, Kimberley Woodcroft, and Michelle Wrenn.

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Authors and Affiliations

  1. Department of Public Health Sciences, Henry Ford Health System, One Ford Place, 3E, Detroit, MI, 48202, USA

    Sharon Hensley Alford, George Divine, Yun Wang, Suzanne Havstad, Karen Wells & Christine Cole Johnson

  2. Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA

    Chun Chao

  3. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA

    Laurel A. Habel

  4. Hematology/Oncology, Henry Ford Hospital, Detroit, MI, USA

    Nalini Janakiraman

  5. Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA

    Heather Spencer Feigelson

  6. Kaiser Permanente Washington, KPWA Health Research Institute, Seattle, WA, USA

    Delia Scholes

  7. School of Public Health, Georgia State University, Atlanta, GA, USA

    Doug Roblin

  8. Department of Medicine, The Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester, MA, USA

    Mara M. Epstein

  9. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Lawrence Engel

  10. School of Public Health, Epidemiology, Boston University, Boston, MA, USA

    Marianne Ulcickas Yood

  11. RTI-HS, Barcelona, Spain

    Joan Fortuny

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  1. Sharon Hensley Alford
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Consortia

for the Cancer Research Network Lymphoma Study Group

  • Ninah Achacoso
  • , Denise Boudreau
  • , Lie Chen
  • , Melody Eide
  • , James Fraser
  • , Gene Hart
  • , Jill Koshiol
  • , Melissa Preciado
  • , Junling Ren
  • , Zaineb Sharafali
  • , Leslie Spangler
  • , David Tabano
  • , Noah Weston
  • , Kimberley Woodcroft
  •  & Michelle Wrenn

Corresponding author

Correspondence to Christine Cole Johnson.

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Conflict of interest

The authors of this manuscript have no conflicts of interest to report.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Additional information

Joan Fortuny and Christine Cole Johnson are the co-senior authors.

A list of the additional members of the Cancer Research Network Lymphoma Study Group appears in the Acknowledgements.

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Alford, S.H., Divine, G., Chao, C. et al. Serum cholesterol trajectories in the 10 years prior to lymphoma diagnosis. Cancer Causes Control 29, 143–156 (2018). https://doi.org/10.1007/s10552-017-0987-7

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