Cancer Causes & Control

, Volume 29, Issue 1, pp 143–156 | Cite as

Serum cholesterol trajectories in the 10 years prior to lymphoma diagnosis

  • Sharon Hensley Alford
  • George Divine
  • Chun Chao
  • Laurel A. Habel
  • Nalini Janakiraman
  • Yun Wang
  • Heather Spencer Feigelson
  • Delia Scholes
  • Doug Roblin
  • Mara M. Epstein
  • Lawrence Engel
  • Suzanne Havstad
  • Karen Wells
  • Marianne Ulcickas Yood
  • Joan Fortuny
  • Christine Cole Johnson
  • for the Cancer Research Network Lymphoma Study Group
Original paper



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.


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.


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.


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.


Cholesterol Lymphoma Hodgkin lymphoma Non-Hodgkin lymphomas 



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.

Compliance with ethical standards

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.

Supplementary material

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Sharon Hensley Alford
    • 1
  • George Divine
    • 1
  • Chun Chao
    • 2
  • Laurel A. Habel
    • 3
  • Nalini Janakiraman
    • 4
  • Yun Wang
    • 1
  • Heather Spencer Feigelson
    • 5
  • Delia Scholes
    • 6
  • Doug Roblin
    • 7
  • Mara M. Epstein
    • 8
  • Lawrence Engel
    • 9
  • Suzanne Havstad
    • 1
  • Karen Wells
    • 1
  • Marianne Ulcickas Yood
    • 10
  • Joan Fortuny
    • 11
  • Christine Cole Johnson
    • 1
  • for the Cancer Research Network Lymphoma Study Group
  1. 1.Department of Public Health SciencesHenry Ford Health SystemDetroitUSA
  2. 2.Department of Research and EvaluationKaiser Permanente Southern CaliforniaPasadenaUSA
  3. 3.Division of ResearchKaiser Permanente Northern CaliforniaOaklandUSA
  4. 4.Hematology/OncologyHenry Ford HospitalDetroitUSA
  5. 5.Institute for Health ResearchKaiser Permanente ColoradoDenverUSA
  6. 6.Kaiser Permanente WashingtonKPWA Health Research InstituteSeattleUSA
  7. 7.School of Public HealthGeorgia State UniversityAtlantaUSA
  8. 8.Department of Medicine, The Meyers Primary Care InstituteUniversity of Massachusetts Medical SchoolWorcesterUSA
  9. 9.Department of Epidemiology, Gillings School of Global Public HealthUniversity of North Carolina at Chapel HillChapel HillUSA
  10. 10.School of Public Health, EpidemiologyBoston UniversityBostonUSA
  11. 11.RTI-HSBarcelonaSpain

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