Sharon Hensley Alford1, George Divine1, Chun Chao2, Laurel A Habel3, Nalini Janakiraman4, Yun Wang1, Heather Spencer Feigelson5, Delia Scholes6, Doug Roblin7, Mara M Epstein8, Lawrence Engel9, Suzanne Havstad1, Karen Wells1, Marianne Ulcickas Yood10, Joan Fortuny11, Christine Cole Johnson12. 1. Department of Public Health Sciences, Henry Ford Health System, One Ford Place, 3E, Detroit, MI, 48202, USA. 2. Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA. 3. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA. 4. Hematology/Oncology, Henry Ford Hospital, Detroit, MI, USA. 5. Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA. 6. Kaiser Permanente Washington, KPWA Health Research Institute, Seattle, WA, USA. 7. School of Public Health, Georgia State University, Atlanta, GA, USA. 8. Department of Medicine, The Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester, MA, USA. 9. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 10. School of Public Health, Epidemiology, Boston University, Boston, MA, USA. 11. RTI-HS, Barcelona, Spain. 12. Department of Public Health Sciences, Henry Ford Health System, One Ford Place, 3E, Detroit, MI, 48202, USA. cjohnso1@hfhs.org.
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.
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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