The following is a summary of “Associations between dysregulation of human blood metabolites and lung cancer risk: evidence from genetic data,” published in the July 2024 issue of Oncology by Wu et al.
Metabolic dysregulation has emerged as a significant contributor to cancer progression, yet the specific causal links between blood metabolites and lung cancer risk remain inadequately defined. This study aimed to address this issue by leveraging extensive genomic datasets to investigate the associations between blood metabolites and lung cancer susceptibility. Researchers analyzed data from 29,266 patients with lung cancer and 56,450 control individuals from the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium (TRICL-ILCCO), with subsequent validation using additional datasets from the FinnGen consortium. The investigation focused on 486 distinct blood metabolites and their correlations with overall lung cancer risk and its major clinical subtypes. To ensure the robustness of the findings, the study group applied multiple Mendelian randomization methods, including inverse-variance weighting, weighted median estimation, and MR-Egger regression.
The analysis identified 19 metabolites with significant associations with lung cancer risk. Elevated levels of oleate (odds ratio [OR] per standard deviation [SD] = 2.56, 95% confidence interval [CI]: 1.51–4.36), 1-arachidonoylglyceropholine (OR = 1.79, 95% CI: 1.22–2.65), and arachidonate (OR = 1.67, 95% CI: 1.16–2.40) were associated with a heightened risk of developing lung cancer. Conversely, lower levels of 1-linoleoylglycerophosphoethanolamine (OR = 0.57, 95% CI: 0.40–0.82), ADpSGEGDFXAEGGGVR, a fibrinogen cleavage peptide (OR = 0.60, 95% CI: 0.47–0.77), and isovalerylcarnitine (OR = 0.62, 95% CI: 0.49–0.78) correlated with a reduced risk of the disease. Notably, isoleucine (OR = 9.64, 95% CI: 2.55–36.38) was strongly associated with an increased risk of lung squamous cell carcinoma, while acetyl phosphate (OR = 0.11, 95% CI: 0.01–0.89) was linked to a significantly lower risk of small cell lung cancer.
These findings reveal complex relationships between specific blood metabolites and lung cancer risk, suggesting their potential utility as biomarkers for lung cancer prevention, early detection, and therapeutic interventions. By elucidating the metabolic pathways involved, the study deepens the understanding of the metabolic mechanisms driving lung cancer and opens new avenues for targeted treatment strategies. This comprehensive analysis underscores the importance of integrating metabolic profiling into cancer risk assessment and management to enhance patient outcomes.
Source: bmccancer.biomedcentral.com/articles/10.1186/s12885-024-12416-1
