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.
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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.
Conflict of interest
The authors of this manuscript have no conflicts of interest to report.
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.
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
- Hodgkin lymphoma
- Non-Hodgkin lymphomas