Low Lipid Profile and Cancer Risk
The evidence indicates that abnormally low HDL cholesterol is positively associated with increased cancer risk, while very low LDL cholesterol achieved through genetic mechanisms or pharmacologic therapy does not increase cancer risk. 1, 2
HDL Cholesterol and Cancer Risk
Low HDL cholesterol levels are consistently associated with increased cancer incidence across multiple studies. The relationship is particularly concerning for HDL levels below 35 mg/dL:
Patients with HDL <35 mg/dL demonstrate significantly higher rates of cancers from digestive organs, breast, skin, urinary tract, and lymphoid/hematopoietic tissue. 2
Extremely low HDL-C levels (<30 mg/dL) are associated with a 3-fold increased risk of total mortality, though this association includes cardiovascular and stroke mortality rather than cancer-specific mortality. 3
A 2013 meta-analysis found that low HDL levels (≤1.03 mmol/L or approximately 40 mg/dL) were associated with a 15% increased risk of obesity-related cancers (RR 1.15,95% CI: 1.01-1.32). 4
The mechanism appears related to HDL's role beyond simple cholesterol transport—low HDL is associated with elevated inflammatory markers (C-reactive protein, fibrinogen, white blood cell count), which may mediate cancer risk. 3
LDL Cholesterol and Cancer Risk
Very low LDL cholesterol does not increase cancer risk, whether achieved genetically or pharmacologically:
The Cholesterol Treatment Trialists' (CTT) meta-analysis of multiple statin trials found no correlation between statin therapy and cancer incidence at any site (RR 1.00,95% CI 0.96-1.04). 1
Individuals with PCSK9 loss-of-function mutations who have LDL-C levels as low as 14 mg/dL demonstrate lower cardiovascular event rates with no increased cancer risk. 5
Long-term follow-up studies including IMPROVE-IT, FOURIER, and ODYSSEY OUTCOMES found no association between achieved LDL-C levels (including <20 mg/dL) and cancer incidence. 1
A Mendelian randomization analysis showed lower LDL-C associated with higher risk only for endometrial cancer of all histologies combined, but this was not replicated in clinical trials. 1
Total Cholesterol and Triglycerides
The relationship between total cholesterol and cancer is inverse—higher total cholesterol appears protective:
Patients with total cholesterol >250 mg/dL had significantly lower cancer probability, particularly for respiratory organ and urinary tract cancers. 2
Elevated triglycerides (≥1.71 mmol/L or approximately 150 mg/dL) were associated with a 20% increased risk of obesity-related cancers (RR 1.20,95% CI: 1.07-1.35). 4
However, in the Women's Health Initiative subcohort, after adjusting for confounders and excluding preclinical disease, most lipid-cancer associations were attenuated except for triglycerides with kidney cancer (HR 3.21,95% CI 1.63-6.33). 6
Clinical Context and Interpretation
The observed associations between low lipids and cancer likely reflect reverse causation rather than direct causation in many cases:
Hypocholesterolemia has been observed in patients with cancers of various organs, suggesting that cancer itself may lower lipid levels rather than low lipids causing cancer. 7
In oral cancer patients, total lipids, cholesterol, and HDL were significantly lower compared to controls, indicating that the neoplastic process itself alters lipid metabolism. 7
Clinical Recommendations
When encountering patients with low lipid profiles, the following approach is warranted:
For HDL <40 mg/dL in men or <45-50 mg/dL in women, assess for secondary causes including hyperglycemia, diabetes, hypertriglyceridemia, very low-fat diets, excess body weight, and smoking. 8, 9
Implement lifestyle interventions: weight loss if overweight, increased physical activity, smoking cessation, and moderate alcohol consumption if appropriate. 9
Do not withhold statin therapy or discontinue PCSK9 inhibitors due to concerns about very low LDL-C and cancer risk—the evidence does not support this concern. 1, 5
Consider cancer screening appropriate for age and risk factors in patients with persistently low HDL cholesterol, particularly HDL <35 mg/dL, given the consistent association with increased cancer incidence. 2
Recognize that extremely high HDL-C levels (≥100 mg/dL) are also associated with increased mortality and inflammatory markers, suggesting a U-shaped relationship. 3
Important Caveats
The lipid-cancer relationship varies by cancer type and ethnicity. Mexican-American patients with HDL 30-40 mg/dL had higher mortality risk than those with very low HDL (<30 mg/dL), demonstrating an "HDL paradox" in this population. 3
Cholesterol in the diet has little evidence linking it specifically to cancer risk, though foods high in cholesterol (processed and red meats) are associated with certain cancers through other mechanisms. 1