{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T06:02:14Z","timestamp":1776492134673,"version":"3.51.2"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,31]],"date-time":"2021-01-31T00:00:00Z","timestamp":1612051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>(1) Background: There is evidence that abnormality in lipid metabolism promotes cancer development. This study investigated whether lipid level and its variability are associated with the development of MM at a population level. (2) Methods: A retrospective cohort study included a total of 3,527,776 subjects aged 40 and above who participated in \u22653 health examinations within the previous five years, including the index year (2012\u20132013). Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) were measured, and visit-to-visit lipid variability were calculated by variability independent of the mean (VIM) method. The study population was followed from the health examination date in the index year until the diagnosis of MM, death, or the last follow-up date (31 December 2017). (3) Results: During a median (5\u201395%) 5.1 years of follow-up, 969 subjects developed MM. A lower risk of MM was observed with higher quartiles of baseline lipid levels compared to the lowest quartile group (Q4 vs. Q1: adjusted hazard ratios (aHRs) 0.51, 95% confidence interval (CI) (0.42\u20130.61) for TC; 0.50 (0.41\u20130.61) for HDL-C; 0.65 (0.54\u20130.77) for LDL-C; and 0.72 (0.60\u20130.87) for TG in model (3). Among all lipid measures, only variability in HDL-C was associated with risk of MM: aHRs (95% CI) were 1.12 (0.91\u20131.38), 1.19 (0.97\u20131.46), and 1.34 (1.09\u20131.65) in the Q2, Q3, and Q4, respectively, compared to the Q1 of VIM of HDL-C. (4) Conclusions: This study shows that patients with lower lipid levels and high HDL-C variability are at increased risk of developing MM.<\/jats:p>","DOI":"10.3390\/cancers13030540","type":"journal-article","created":{"date-parts":[[2021,1,31]],"date-time":"2021-01-31T21:31:56Z","timestamp":1612128716000},"page":"540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Lipid Level, Lipid Variability, and Risk of Multiple Myeloma: A Nationwide Population-Based Study of 3,527,776 Subjects"],"prefix":"10.3390","volume":"13","author":[{"given":"Taewoong","family":"Choi","sequence":"first","affiliation":[{"name":"Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 04514, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyungdo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Statistics and Actuarial Science, Soongsil University, Seoul 06978, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su-Min","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul 07061, Korea"},{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Eun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 06236, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Youl","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul 02453, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Gyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, College of Medicine, Catholic University of Korea, Seoul 06591, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Wook","family":"Shin","sequence":"additional","affiliation":[{"name":"Supportive Care Center\/Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"},{"name":"Department of Clinical Research Design &amp; Evaluation, Samsung Advanced Institute for Health Science &amp; Technology (SAIHST), Sungkyunkwan University, Seoul 06355, Korea"},{"name":"Department of Digital Health, Samsung Advanced Institute for Health Science &amp; Technology (SAIHST), Sungkyunkwan University, Seoul 06355, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,31]]},"reference":[{"key":"ref_1","unstructured":"(2019, April 01). Surveillance, Epidemiology, and End Results (SEER) Program Research Data (1975\u20132016), Available online: www.seer.cancer.gov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41408-018-0155-7","article-title":"Clinical predictors of long-term survival in newly diagnosed transplant eligible multiple myeloma\u2014an IMWG Research Project","volume":"8","author":"Usmani","year":"2018","journal-title":"J. Blood Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e431","DOI":"10.1016\/S2352-3026(17)30140-0","article-title":"Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: A randomised, double-blind, phase 3 trial","volume":"4","author":"Holstein","year":"2017","journal-title":"Lancet Haematol."},{"key":"ref_4","first-page":"778","article-title":"Lipid metabolism and car-cinogenesis, cancer development","volume":"8","author":"Long","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.canlet.2016.11.033","article-title":"VLDL and LDL, but not HDL, promote breast cancer cell proliferation, metastasis and angiogenesis","volume":"388","author":"Lu","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_6","first-page":"1","article-title":"Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential: A molecular and clinicopathological study","volume":"15","author":"Nasarre","year":"2015","journal-title":"BMC Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1038\/labinvest.2009.97","article-title":"Free fatty acids enhance breast cancer cell migration through plasminogen activator inhibitor-1 and SMAD4","volume":"89","author":"Byon","year":"2009","journal-title":"Lab. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1200\/JCO.2010.31.5200","article-title":"Total cholesterol and cancer risk in a large prospective study in Korea","volume":"29","author":"Kitahara","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1093\/jnci\/djh216","article-title":"Serum high-density lipoprotein cholesterol, metabolic profile, and breast cancer risk","volume":"96","author":"Furberg","year":"2004","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2217\/17520363.1.1.121","article-title":"Low high-density lipoprotein cholesterol may signal breast cancer risk: Recent findings and new hypotheses","volume":"1","author":"Furberg","year":"2007","journal-title":"Biomarkers Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1158\/1055-9965.EPI-08-0133","article-title":"Serum high-density lipoprotein cholesterol and breast cancer risk by menopausal status, body mass index, and hormonal receptor in Korea","volume":"18","author":"Kim","year":"2009","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cmet.2014.01.019","article-title":"Cholesteryl ester accumulation induced by pten loss and PI3K\/AKT activation underlies human prostate cancer aggressiveness","volume":"19","author":"Yue","year":"2014","journal-title":"Cell Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.1002\/ijc.30709","article-title":"Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer","volume":"140","author":"Law","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/sj.bjc.6605264","article-title":"Serum triglyceride concentrations and cancer risk in a large cohort study in Austria","volume":"101","author":"Ulmer","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Liu, X., Xu, P., Wang, L., Zhang, C., Wang, M., Ouyang, J., and Chen, B. (2020). Cholesterol levels provide prognostic information in patients with multiple myeloma. Clin. Lab., 66.","DOI":"10.7754\/Clin.Lab.2019.190824"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00280-003-0692-y","article-title":"Me-tabolism of a cholesterol-rich microemulsion (LDE) in patients with multiple myeloma and a pre-liminary clinical study of LDE as a drug vehicle for the treatment of the disease","volume":"53","author":"Hungria","year":"2004","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_17","first-page":"223","article-title":"Cholesterol levels in patients with multiple myeloma","volume":"87","author":"Tombuloglu","year":"2007","journal-title":"Ann. Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s10552-017-0991-y","article-title":"Serum lipids and risk of obesity-related cancers in postmenopausal women","volume":"29","author":"Kabat","year":"2017","journal-title":"Cancer Causes Control."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-020-00963-6","article-title":"Low high-density lipoprotein and in-creased risk of several cancers: 2 population-based cohort studies including 116,728 individuals","volume":"13","author":"Pedersen","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Jeong, S.C.T., Kim, D., Han, K., Kim, S.J., Rhee, S.Y., Giovannucci, E.L., and Shin, D.W. (2020). Association between high-density lipoprotein cholesterol level and risk of hematologic malignancy. Leukemia.","DOI":"10.1038\/s41375-020-01081-5"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S0009-9120(99)00030-2","article-title":"Monthly intra-individual variation in lipids over a 1-year period in 22 normal subjects","volume":"32","author":"Nazir","year":"1999","journal-title":"Clin. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1093\/clinchem\/39.6.1012","article-title":"Biological variability in concentrations of serum lipids: Sources of variation among results from published studies and composite predicted values","volume":"39","author":"Smith","year":"1993","journal-title":"Clin. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jacl.2018.01.001","article-title":"Visit-to-visit lipid variability: Clinical significance, effects of lipid-lowering treatment, and (pharmaco) genetics","volume":"12","author":"Smit","year":"2018","journal-title":"J. Clin. Lipidol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.jacc.2015.02.017","article-title":"Visit-to-visit low-density lipoprotein cholesterol variability and risk of cardiovascular outcomes","volume":"65","author":"Bangalore","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.amjcard.2016.10.037","article-title":"Relation of variability of low-density lipoprotein cholesterol and blood pressure to events in patients with previous myocardial infarction from the ideal trial","volume":"119","author":"Bangalore","year":"2017","journal-title":"Am. J. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/0002-8703(94)90393-X","article-title":"Long-term intraindividual cholesterol varia-bility: Natural course and adverse impact on morbidity and mortality--the Framingham Study","volume":"127","author":"Kreger","year":"1994","journal-title":"Am. Heart J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3560","DOI":"10.1093\/eurheartj\/ehx585","article-title":"Cholesterol variability and the risk of mortality, myocardial infarction, and stroke: A nationwide population-based study","volume":"38","author":"Kim","year":"2017","journal-title":"Eur. Hear. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1161\/ATVBAHA.117.309803","article-title":"Variability in total cholesterol is associated with the risk of end-stage renal disease","volume":"37","author":"Kim","year":"2017","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_29","first-page":"799","article-title":"Data resource profile: The national health information database of the national health insurance service in south korea","volume":"46","author":"Seong","year":"2016","journal-title":"Int. J. Epidemiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1002\/mds.27681","article-title":"Association of statin use with Parkinson\u2019s disease: Dose\u2013response relationship","volume":"34","author":"Jeong","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_31","first-page":"1","article-title":"Anemia is associated with incidence of dementia: A national health screening study in Korea involving 37,900 persons","volume":"9","author":"Jeong","year":"2017","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1002\/ijc.31180","article-title":"Waist circumference and risk of breast cancer in Korean women: A nationwide cohort study","volume":"142","author":"Lee","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1158\/1055-9965.EPI-13-0699","article-title":"Physical activity in relation to risk of hematologic cancers: A systematic review and meta-analysis","volume":"23","author":"Jochem","year":"2014","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1634\/theoncologist.2010-0206","article-title":"Obesity and the Risk for a Hematological Malignancy: Leukemia, Lymphoma, or Myeloma","volume":"15","author":"Lichtman","year":"2010","journal-title":"Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.freeradbiomed.2006.07.006","article-title":"Antioxidant and cytoprotective properties of high-density lipoproteins in vascular cells","volume":"41","author":"Salvayre","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"977","DOI":"10.37358\/RC.19.3.7043","article-title":"The evaluation of oxidative stress and high-density lipoprotein cholesterol levels in diffuse large b-cell lymphoma","volume":"70","author":"Gaman","year":"2019","journal-title":"Revista de Chimie"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/978-3-0348-0837-8_13","article-title":"The role of inflammation in leukaemia","volume":"816","author":"Giles","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1126\/science.1189731","article-title":"ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation","volume":"328","author":"Pagler","year":"2010","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1146\/annurev-nutr-071811-150709","article-title":"New roles of HDL in inflammation and hematopoiesis","volume":"32","author":"Zhu","year":"2012","journal-title":"Annu. Rev. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1172\/JCI113682","article-title":"Serum prostacyclin stabilizing factor is identical to apolipoprotein A-I (Apo A-I). A novel function of Apo A-I","volume":"82","author":"Yui","year":"1988","journal-title":"J. Clin. Investig."},{"key":"ref_41","first-page":"379","article-title":"Blood lipid profiles in children with acute lymphoblastic leukemia","volume":"83","author":"Halton","year":"1998","journal-title":"Cancer Interdiscip. Int. J. Am. Cancer Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1242\/dmm.011338","article-title":"Hooked on fat: The role of lipid synthesis in cancer metabolism and tumour development","volume":"6","author":"Baenke","year":"2013","journal-title":"Dis. Model. Mech."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cccn.2005.04.003","article-title":"Cholesteryl esters in malignancy","volume":"359","author":"Tosi","year":"2005","journal-title":"Clin. Chim. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"20563","DOI":"10.18632\/oncotarget.25003","article-title":"Inhibition of mTOR complex 2 restrains tumor angiogenesis in multiple myeloma","volume":"9","author":"Lamanuzzi","year":"2018","journal-title":"Oncotarget"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.1080\/10428194.2017.1421760","article-title":"PI3K\/AKT\/mTOR pathway in multiple myeloma: From basic biology to clinical promise","volume":"59","author":"Ramakrishnan","year":"2018","journal-title":"Leuk. Lymphoma"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s11899-016-0315-4","article-title":"Signaling pathways and emerging therapies in multiple myeloma","volume":"11","author":"Ramakrishnan","year":"2016","journal-title":"Curr. Hematol. Malign-Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.bbalip.2014.03.014","article-title":"Inhibition of mTOR down-regulates scavenger receptor, class B, type I (SR-BI) expression, reduces endothelial cell migration and impairs nitric oxide production","volume":"1841","author":"Krieger","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA) Bioenergy"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1016\/j.ejca.2010.03.041","article-title":"Severe hypocholesterolaemia is often neglected in haematological malignancies","volume":"46","author":"Pugliese","year":"2010","journal-title":"Eur. J. Cancer"},{"key":"ref_49","first-page":"1","article-title":"Why high cholesterol levels help hematological malignancies: Role of nuclear lipid microdomains","volume":"15","author":"Codini","year":"2016","journal-title":"Lipids Heal. Dis."},{"key":"ref_50","first-page":"23","article-title":"Cholesterol levels in patients with chronic lymphocytic leukemia","volume":"109","author":"Sargin","year":"2017","journal-title":"J. Natl. Med. Assoc."},{"key":"ref_51","first-page":"343","article-title":"Return to normal values of li-pid pattern after effective chemotherapy in acute lymphoblastic leukemia","volume":"81","author":"Scribano","year":"1996","journal-title":"Haematologica"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/0002-9343(82)90543-5","article-title":"Plasma lipid alterations in leukemia and lymphoma","volume":"72","author":"Spiegel","year":"1982","journal-title":"Am. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4198","DOI":"10.1182\/blood.V126.23.4198.4198","article-title":"Long term statin use and risk of multiple myeloma among 15.5 million taiwanese adults: A retrospective cohort study","volume":"126","author":"Chiu","year":"2015","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/ijc.30745","article-title":"Statin use and risk of multiple myeloma: An analysis from the cancer research network","volume":"141","author":"Epstein","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4008","DOI":"10.1200\/JCO.2016.68.3482","article-title":"Statins are associated with reduced mortality in multiple myeloma","volume":"34","author":"Sanfilippo","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_56","unstructured":"NCD Risk Factor Collaboration (NCD-RisC), and Gutierrez, L. (2020). Repositioning of the global epicentre of non-optimal cholesterol. Nat. Cell Biol., 582, 73\u201377."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ijge.2018.02.010","article-title":"Epidemiology of dyslipidemia in the Asia Pacific region","volume":"12","author":"Lin","year":"2018","journal-title":"Int. J. Gerontol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/3\/540\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:17:58Z","timestamp":1760159878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/3\/540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,31]]},"references-count":57,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["cancers13030540"],"URL":"https:\/\/doi.org\/10.3390\/cancers13030540","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,31]]}}}