Deciphering bidirectional causal links between oxidative stress and lung cancer risk through Mendelian randomization

TL;DR

This study uses genetic data to show how oxidative stress biomarkers are linked to different types of lung cancer, suggesting new prevention strategies.

Contribution

The study identifies specific causal links between oxidative stress biomarkers and lung cancer subtypes using bidirectional Mendelian randomization.

Findings

Higher albumin levels are linked to reduced adenocarcinoma risk.

Elevated monounsaturated fatty acids increase squamous cell carcinoma risk.

Increased lactate levels are associated with higher small cell lung cancer risk.

Abstract

Lung cancer remains the leading cause of cancer-related mortality globally. Despite advancements in treatment, survival rates for advanced-stage disease remain suboptimal, emphasizing the need for novel prevention strategies. Oxidative stress (OS), resulting from an imbalance between reactive oxygen species (ROS) and antioxidants, is implicated in lung cancer pathogenesis. This study aimed to explore bidirectional causal relationships between genetically predicted oxidative stress injury biomarkers (OSIBs) and lung cancer risk using mendelian randomization (MR).

A two-sample bidirectional MR approach was used to assess causal effects of 16 OSIBs on lung cancer subtypes (small cell lung cancer, squamous cell carcinoma, and adenocarcinoma) and vice versa. Genetic data were derived from large-scale genome-wide association studies in European populations.

MR analysis revealed significant associations. Higher albumin levels were associated with reduced adenocarcinoma risk (OR = 0.599, 95%CI: 0.369–0.974, P = 0.039). Elevated monounsaturated fatty acids levels were linked to an increased risk of squamous cell carcinoma (OR = 1.742, 95% CI: 1.095–2.772, P = 0.019). Increased lactate levels were positively associated with small cell lung cancer (OR = 4.565, 95% CI: 1.009–20.657, P = 0.049). Reverse MR analysis did not suggest causal effects of lung cancer on OSIBs.

These findings highlight the distinct roles of OSIBs in lung cancer risk and underscore oxidative stress's pivotal role in cancer development. Further research is needed to validate these biomarkers for early detection and preventive strategies.

The online version contains supplementary material available at 10.1007/s12672-025-03289-2.

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