Regulatory T Cell-Related Gene Polymorphisms are Associated with Risk of Lung Cancer in Patients with COPD

Background: The chronic inflammatory state of COPD can lead to an imbalance in immune cell subsets, specifically manifested as an increase in regulatory T cells (Tregs), which may promote tumor immune escape. However, few studies have reported the correlation between polymorphisms of Treg-related FOXP3, IL2 , and TGFB1 genes and the risk of lung cancer in COPD patients. Methods: Six SNPs in FOXP3, IL2 , and TGFB1 were genotyped in 582 patients with COPD combined with lung cancer (the study group) and 603 patients with simple COPD (the control group) using a MassARRAY platform. Results: By comparing the allele frequencies of the study group and the control group, three SNPs were found to be associated with the risk of lung cancer in patients with COPD, including FOXP3 -rs3761547, IL2 -rs2069762 and TGFB1 -rs4803455 ( p < 0.0001). Genotype frequencies analysis revealed that FOXP3 -rs3761547-TC/CC, IL2 -rs2069762-AC/CC and TGFB1 -rs4803455-CA/AA genotypes were associated with increased risk of lung cancer in COPD patients ( p < 0.0001). Moreover, genetic model analysis results showed that FOXP3 -rs3761547 had the highest risk of causing lung cancer in COPD patients in the recessive model, at 2.68 times ( p < 0.0001). IL2 -rs2069762 and TGFB1 -rs4803455 had the highest pathogenic risks in the dominant model, at 2.11 and 3.27 times respectively ( p < 0.0001). Additionally, stratified analyses showed that the three SNPs were significantly associated with the risk of lung cancer in both smoking and non-smoking COPD patients ( p < 0.0001), and the risk of lung squamous cell carcinoma and lung adenocarcinoma in COPD patients ( p < 0.001). Conclusion: Our results suggest that Treg-related genes polymorphisms may serve as susceptibility markers for lung cancer in the COPD population. Keywords: COPD, single nucleotide polymorphisms, SNPs, lung cancer, FOXP3 , IL2 , TGFB1