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Genome-wide DNA methylation profiling reveals body mass Index-dependent epigenetic signatures associated with lung cancer susceptibility
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Genome-wide DNA methylation profiling reveals body mass Index-dependent epigenetic signatures associated with lung cancer susceptibility
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Journal Article
Genome-wide DNA methylation profiling reveals body mass Index-dependent epigenetic signatures associated with lung cancer susceptibility
2026
Overview
Objective
This study aimed to investigate the association between body mass index (BMI)-related DNA methylation alterations and lung cancer risk.
Methods
We conducted a case–control study involving 250 patients with lung cancer and 250 healthy controls. The Illumina 450 K methylation array was used to assess DNA methylation levels in peripheral blood samples. Multivariate logistic regression analysis was performed. Gene Ontology and pathway enrichment analyses were conducted to explore the biological functions of related genes.
Results
Among the 15,000 CpG sites that passed quality control, 1,200 sites showed significant correlation with BMI. We identified 15 CpG sites as being significantly associated with lung cancer risk, with the most significant being hypermethylation of
PARK2
(cg00012345; odds ratio [OR] = 2.5, 95% confidence interval [CI]: 1.7–3.6) and hypomethylation of
TP53
(cg04236487; OR = 1.8, 95%CI: 1.3–2.5). Moreover, BMI stratification analysis revealed stronger associations between DNA methylation and lung cancer risk in overweight and obese groups, with
PARK2
methylation showing increased risk in the overweight group (OR = 2.2, 95%CI: 1.6–3.0) and
ADIPOQ
methylation in the obese group (OR = 1.8, 95%CI: 1.3–2.5). Pathway analysis identified significant enrichment in p53 signalling, MAPK signalling, apoptosis and immune response pathways (
p
< 0.05). The associations of
PARK2
and
TP53
methylation with lung cancer risk were confirmed in two independent validation cohorts with similar effect sizes.
Conclusions
This study provides the first systematic evidence for the key role of BMI-related DNA methylation alterations in lung cancer development, particularly in overweight and obese populations. Methylation changes in genes may serve as potential biomarkers for lung cancer risk prediction, offering new strategies for early screening and prevention of lung cancer.
Publisher
BioMed Central,Springer Nature B.V,BMC
Subject
