Lipid Metabolism and Cancer Risk

Lipid metabolism encompasses the synthesis, transport and utilisation of fats and cholesterol within the body, processes that malignant tissues reprogramme to support rapid proliferation. Cancer cells often upregulate cholesterol biosynthesis pathways, enhance uptake of lipoprotein particles and shift fatty acid oxidation to fuel membrane biogenesis, energy production and oncogenic signalling. Circulating lipoproteins—particularly high-density lipoprotein (HDL) and low-density lipoprotein (LDL)—serve both as biomarkers and active mediators of tumour biology. Altered systemic lipid profiles have been linked to incidence, progression and prognosis across a range of malignancies, from breast and gastrointestinal cancers to colorectal disease. Genetic and epidemiological evidence suggests causal roles for dyslipidaemia in carcinogenesis, raising the prospect that cholesterol-modulating interventions may offer preventive or therapeutic benefit. The global significance of this field lies in its translational potential, spanning early detection through lipid profiling to targeted metabolic therapies that address tumour-specific lipid dependencies.

Research from Nature Portfolio

Longitudinal population data indicate that individuals with persistently low HDL-C, or whose HDL-C declines from normal to low, face significantly elevated risks of gastric, colorectal, liver, pancreatic and biliary cancers, with risk modulated by age, sex and smoking status. Mendelian randomisation studies have revealed that genetically raised LDL-cholesterol and, unexpectedly, genetically raised HDL-cholesterol are both associated with higher breast cancer risk, suggesting that lipid-lowering strategies and clinical trials of lipid-modifying agents should consider cancer outcomes. In colorectal cancer, reduced serum apolipoprotein A-I levels independently predict advanced tumour stage, heightened systemic inflammation and poorer survival, highlighting its promise as a prognostic biomarker and potential target for intervention.

Lipid Metabolism and Cancer Risk publication trend

The graph below shows the total number of articles in lipid metabolism and cancer risk across all publications each year (not limited to Nature Index journals).

Technical terms

Lipid metabolism: The suite of biochemical pathways involved in the synthesis, transport and degradation of lipids and cholesterol.

High-density lipoprotein (HDL): A class of lipoprotein particles that mediates reverse cholesterol transport from peripheral tissues to the liver.

Low-density lipoprotein (LDL): Lipoprotein particles that deliver cholesterol to cells and, when elevated, can be co-opted by tumours to support growth.

Very low-density lipoprotein (VLDL): Triglyceride-rich lipoprotein particles that serve as precursors to LDL.

Apolipoprotein A-I (ApoA-I): The principal protein component of HDL, essential for cholesterol efflux and immunomodulatory activity.

Mendelian randomisation: A genetic epidemiological technique using inherited variants to infer causal effects of modifiable exposures on disease risk.

NMR metabolomics: The use of nuclear magnetic resonance spectroscopy to profile metabolites, including lipoprotein subfractions, in biological samples.

Risk stratification: The process of categorising individuals according to their probability of developing a disease to guide screening and preventive measures.

References

1. The role of cholesterol metabolism and cholesterol transport in carcinogenesis: a review of scientific findings, relevant to future cancer therapeutics. Frontiers in Pharmacology (2013).
2. Blood lipids and lipoproteins in relation to incidence and mortality risks for CVD and cancer in the prospective EPIC–Heidelberg cohort. BMC Medicine (2017).
3. A population-based cohort study of longitudinal change of high-density lipoprotein cholesterol impact on gastrointestinal cancer risk. Nature Communications (2024).
4. A Mendelian randomization study of the effects of blood lipids on breast cancer risk. Nature Communications (2018).
5. Decreased serum apolipoprotein A1 levels are associated with poor survival and systemic inflammatory response in colorectal cancer. Scientific Reports (2017).
6. VLDL and LDL Subfractions Enhance the Risk Stratification of Individuals Who Underwent Epstein–Barr Virus‐Based Screening for Nasopharyngeal Carcinoma: A Multicenter Cohort Study. Advanced Science (2024).
7. Apolipoprotein A-I (ApoA-I), Immunity, Inflammation and Cancer. Cancers (2019).
8. The Cardioprotective Protein Apolipoprotein A1 Promotes Potent Anti-tumorigenic Effects* ♦. Journal of Biological Chemistry (2013).
9. HDL and LDL: Potential New Players in Breast Cancer Development. Journal of Clinical Medicine (2019).