Serum cholesterol trajectories in the 10 years prior to lymphoma diagnosis
- 137 Downloads
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.
KeywordsCholesterol 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.
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.
- 9.Strohmaier S, Edlinger M, Manjer J, Stocks T, Bjørge T, Borena W, Häggström C, Engeland A, Nagel G, Almquist M, Selmer R, Tretli S, Concin H, Hallmans G, Jonsson H, Stattin P, Ulmer H (2013) Total serum cholesterol and cancer incidence in the metabolic syndrome and cancer project (Me-Can). PLoS ONE 8(1):e54242. https://doi.org/10.1371/journal.pone.0054242 CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Strasak AM, Pfeiffer RM, Brant LJ, Rapp K, Hilbe W, Oberaigner W, Lang S, Borena W, Concin H, Diem G, Ruttmann E, Glodny B, Pfeiffer KP, Ulmer H, Group VPS (2009) Time-dependent association of total serum cholesterol and cancer incidence in a cohort of 172,210 men and women: a prospective 19-year follow-up study. Ann Oncol 20(6):1113–1120. https://doi.org/10.1093/annonc/mdn736 CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Nagel G, Stocks T, Späth D, Hjartåker A, Lindkvist B, Hallmans G, Jonsson H, Bjørge T, Manjer J, Häggström C, Engeland A, Ulmer H, Selmer R, Concin H, Stattin P, Schlenk RF (2012) Metabolic factors and blood cancers among 578,000 adults in the metabolic syndrome and cancer project (Me-Can). Ann Hematol 91(10):1519–1531. https://doi.org/10.1007/s00277-012-1489-z CrossRefPubMedGoogle Scholar
- 15.Morimoto Y, Conroy SM, Ollberding NJ, Henning SM, Franke AA, Wilkens LR, Goodman MT, Hernandez BY, Le Marchand L, Henderson BE, Kolonel LN, Maskarinec G (2012) Erythrocyte membrane fatty acid composition, serum lipids, and non-Hodgkin’s lymphoma risk in a nested case–control study: the multiethnic cohort. Cancer Causes Control 23(10):1693–1703. https://doi.org/10.1007/s10552-012-0048-1 CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Kontush A, Chapman MJ (2012) Structure, metabolism, function, and therapeutics. Wiley, Hoboken, NJGoogle Scholar
- 20.Cockerill GW, Huehns TY, Weerasinghe A, Stocker C, Lerch PG, Miller NE, Haskard DO (2001) Elevation of plasma high-density lipoprotein concentration reduces interleukin-1-induced expression of E-selectin in an in vivo model of acute inflammation. Circulation 103(1):108–112CrossRefPubMedGoogle Scholar
- 22.Lewis GF, Rader DJ (2005) New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res 96(12):1221–1232. https://doi.org/10.1161/01.RES.0000170946.56981.5c CrossRefPubMedGoogle Scholar
- 23.Mathews CK, Van Holde KE, Appling DR, Anthony-Cahill SJ (2013) Biochemistry, 4th edn. Prentice Hall, TorontoGoogle Scholar
- 28.Morton LM, Hartge P, Holford TR, Holly EA, Chiu BC, Vineis P, Stagnaro E, Willett EV, Franceschi S, La Vecchia C, Hughes AM, Cozen W, Davis S, Severson RK, Bernstein L, Mayne ST, Dee FR, Cerhan JR, Zheng T (2005) Cigarette smoking and risk of non-Hodgkin lymphoma: a pooled analysis from the International lymphoma epidemiology consortium (interlymph). Cancer Epidemiol Biomarkers Prev 14(4):925–933. https://doi.org/10.1158/1055-9965.EPI-04-0693 CrossRefPubMedGoogle Scholar
- 31.Willett EV, Morton LM, Hartge P, Becker N, Bernstein L, Boffetta P, Bracci P, Cerhan J, Chiu BC, Cocco P, Dal Maso L, Davis S, De Sanjose S, Smedby KE, Ennas MG, Foretova L, Holly EA, La Vecchia C, Matsuo K, Maynadie M, Melbye M, Negri E, Nieters A, Severson R, Slager SL, Spinelli JJ, Staines A, Talamini R, Vornanen M, Weisenburger DD, Roman E, Consortium I (2008) Non-Hodgkin lymphoma and obesity: a pooled analysis from the InterLymph Consortium. Int J Cancer 122(9):2062–2070. https://doi.org/10.1002/ijc.23344 CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Britton JA, Khan AE, Rohrmann S, Becker N, Linseisen J, Nieters A, Kaaks R, Tjønneland A, Halkjaer J, Severinsen MT, Overvad K, Pischon T, Boeing H, Trichopoulou A, Kalapothaki V, Trichopoulos D, Mattiello A, Tagliabue G, Sacerdote C, Peeters PH, Bueno-de-Mesquita HB, Ardanaz E, Navarro C, Jakszyn P, Altzibar JM, Hallmans G, Malmer B, Berglund G, Manjer J, Allen N, Key T, Bingham S, Besson H, Ferrari P, Jenab M, Boffetta P, Vineis P, Riboli E (2008) Anthropometric characteristics and non-Hodgkin’s lymphoma and multiple myeloma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Haematologica 93(11):1666–1677. https://doi.org/10.3324/haematol.13078 CrossRefPubMedGoogle Scholar