The authors wrote, “Metabolic dysregulation is recognized as a significant hallmark of cancer progression. Although numerous studies have linked specific metabolic pathways to cancer incidence, the causal relationship between blood metabolites and lung cancer risk remains unclear.”
The researchers employed genomic data from 29,266 LC patients and 56,450 control individuals from the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium. The scientists confirmed their results utilizing additional data from the FinnGen consortium, and the study also examined 486 blood metabolites and their correlations with overall LC and its three major clinical subtypes. To ensure the strength of their findings, the researchers employed several Mendelian randomization methods, including inverse-variance weighting, weighted median estimation, and MR-Egger regression.
The results revealed that 19 blood metabolites were detected with significant correlations with the risk of LC. The authors noted that among these metabolites, oleate, 1-arachidonoylglyceropholine, and arachidonate were associated with an augmented risk of LC, while 1-linoleoylglycerophosphoethanolamine—a fibrinogen cleavage peptide known as ADpSGEGDFXAEGGGVR—and isovalerylcarnitine were associated with a lower risk of LC. Additionally, the metabolite isoleucine was discovered to significantly augment the risk of lung squamous cell cancer, while acetyl phosphate was linked with a meaningfully lower risk of small-cell lung cancer.
The authors noted that additional studies should investigate these metabolites across different populations and cancer subtypes to gain more insight into their impacts and potential applications in clinical practice.
Based on their findings, the authors concluded, “Our study provides a novel understanding of the metabolic underpinnings of LC by demonstrating a potential causal link between specific blood metabolites and the risk of developing LC. These insights are pivotal for advancing early detection and preventative strategies. Additionally, our findings could significantly inform the development of targeted treatment approaches, potentially leading to more personalized and effective therapeutic options for LC patients.”
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