Low Cholesterol Levels Associated with Greater Risk of Plasma Cell Neoplasm

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Decreased blood serum cholesterol levels were associated with an increased risk of plasma cell neoplasm, although there was no causal association with multiple myeloma.

Results from a prospective cohort study are providing clinicians with an overview of the association between blood serum cholesterol levels and risk of plasma cell neoplasm.

Although findings showed decreased serum total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A (ApoA), and apolipoprotein B (ApoB) levels were all associated with an increased risk of plasma cell neoplasm, further analysis revealed no causal association with the incidence of multiple myeloma.1

“Although some researchers have indicated there might be a relationship between levels of lipid profiles and hematologic malignancies, studies were mainly focused on the impact of HDL level. Our study was designed to investigate the relationship between various cholesterol metabolism parameters with overall plasma cell neoplasms,” wrote investigators.1

A disease in which the body produces too many plasma cells, plasma cell neoplasm forms tumors in bones and soft tissues and is thought to be caused by antigenic stimulation from infections, chronic disease, radiation, and specific toxic substances. However, the disease’s exact etiology remains unknown and requires further research.2

To assess the association between cholesterol levels and plasma cell neoplasm, Linfeng Li, of West China School of Medicine at Sichuan University, and colleagues examined total cholesterol levels, LDL levels, HDL levels, ApoA, and ApoB as risk factors for plasma cell neoplasms in patients from the UK Biobank, a prospective cohort study involving 502,507 participants aged 40-69 years who were registered with the UK National Health Service in 2006–2010. For inclusion, patients were required to have no record of any prior cancer in national cancer registries except nonmelanoma skin cancer. Those with no serum lipid biomarker assessment or body mass index data were excluded from the study.1

In total, 408,722 participants were enrolled in the study, including 1819 with plasma cell neoplasm. Participants with plasma cell neoplasm were older than noncase participants (62 years of age vs 58 years of age). Additionally, the plasma cell neoplasm group had a greater proportion of male patients compared to the noncase group (55.4% vs 46.3%).1

Investigators used Cox proportional hazard regression and restricted cubic spline model to determine the relationship between plasma cell neoplasms diagnosis and lipid metabolism indicators, further conducting 2-sample Mendelian randomization to assess if cholesterol level had a causal effect on developing plasma cell neoplasms. Lipid metabolism indicators were the primary exposure variables, and the primary outcome was the first diagnosis of any type of plasma cell neoplasm according to International Classification of Disease 10th Revision codes for multiple myeloma, plasma cell leukemia, plasmacytoma, Waldenstrom's macroglobulinemia, amyloidosis, and monoclonal gammopathies.1

Upon analysis, all lipid profiles examined in the study were inversely associated with plasma cell neoplasm risk (all Ptrend < .005). Total cholesterol, LDL, and ApoB levels showed a linear association with the risk of neoplasms (Pnonlinear > .05), while HDL and ApoA levels showed a nonlinear association (Pnonlinear < .05). After adjusting for covariates, investigators noted greater baseline lipid levels were associated with a decreased risk of plasma cell neoplasms:

  • ApoA (adjusted hazard ratio [aHR], 0.82; 95% confidence interval [CI], 0.71–0.95)
  • ApoB (aHR, 0.67; 95% CI, 0.58–0.77)
  • TC (aHR, 0.71; 95% CI, 0.61–0.82)
  • LDL (aHR, 0.66; 95% CI, 0.64–0.88)
  • HDL (aHR, 0.79; 95% CI, 0.68–0.9)
  • Triglycerides (aHR, 0.92; 95% CI, 0.79–1.07)

Of note, Mendelian randomization-Egger and inverse variance weighted mode did not show any statistical significance for ApoA, HDL, LDL, and total cholesterol levels for a causal association with the incidence of multiple myeloma.1

“In the future, further research on the risk of cancer in the treatment of dyslipidemia should be conducted. Furthermore, more research is required to determine the precise molecular mechanism connecting lipid levels with the carcinogenesis of plasma cell neoplasms,” investigators concluded.1


  1. Li L, Yu Z, Ren J, Niu T. Low cholesterol levels are associated with increasing risk of plasma cell neoplasm: A UK biobank cohort study. Cancer Med. 2023;00:1-12. doi:10.1002/cam4.6649
  2. National Library of Medicine. Plasma Cell Cancer. StatPearls. September 26, 2022. Accessed November 9, 2023.