Serum Lipid Levels, Genetic Risk, and Lung Cancer Incidence: A Large Prospective Cohort Study

Area of Science:

• Biomedical Research
• Genetics
• Epidemiology

Background:

• Previous research often examined metabolic factors or genetics independently for lung cancer risk.
• The combined influence of serum lipids and genetic predisposition on lung cancer risk was largely unexplored.

Purpose of the Study:

• To investigate the associations between serum lipid profiles, genetic risk, and the incidence of lung cancer.
• To explore the joint and interactive effects of lipid levels and genetic risk on lung cancer development.

Main Methods:

• Utilized data from 426,524 UK Biobank participants.
• Employed Cox proportional hazards models and restricted cubic splines to analyze lipid-serum associations.
• Constructed a polygenic risk score (PRS) to evaluate combined and interactive effects with serum lipids.

Main Results:

• Elevated apolipoprotein A levels correlated with reduced lung cancer risk.
• An inverse J-shaped association was observed between high-density lipoprotein (HDL) and lung cancer.
• High PRS combined with low total cholesterol, HDL, low-density lipoprotein (LDL), apolipoprotein A, or apolipoprotein B indicated significantly higher lung cancer risks.
• High PRS and elevated triglycerides showed a notably higher risk compared to low PRS and low triglycerides.
• Significant interactions were found between high PRS and low LDL, and high PRS and low apolipoprotein B.

Conclusions:

• Serum lipid levels are significantly associated with lung cancer risk.
• Interactions between low-density lipoprotein (LDL) or apolipoprotein B and genetic risk factors may influence lung cancer development.
• Individuals with higher genetic susceptibility should monitor their lipid profiles closely to mitigate lung cancer risk.