<abstract xmlns="http://www.w3.org/1999/xhtml">

Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are closely related diseases associated with smoking history and dysregulated immune response. However, not all smokers develop the disease, indicating that genetic susceptibility could be important. Therefore, the aim of this study was to search for the potential overlapping genetic biomarkers, with a focus on single nucleotide polymorphisms (SNPs) located in the regulatory regions of immune-related genes. Additionally, the aim was to see if an identified SNP has potentially an effect on proinflamma-tory cytokine concentration in the serum of COPD patients. We extracted summary data of variants in 1511 immune-related genes from COPD and LC genome-wide association studies (GWAS) from the UK Biobank. The LC data had 203 cases, patients diagnosed with LC, and 360 938 controls, while COPD data had 1 897 cases and 359 297 controls. Assuming 1 association/gene, SNPs with a <italic>p</italic>-value &lt; 3.3 × 10–5 were considered statistically significantly associated with the disease. We identified seven SNPs located in different genes (<italic>BAG6, BTNL2, TNF, HCP5, MICB, NCR3, ABCF1, TCF7L1</italic>) to be associated with the COPD risk and two with the LC risk (<italic>HLA-C, HLA-B</italic>), with statistical significance. We also identified two SNPs located in the <italic>IL2RA</italic> gene associated with LC (rs2386841; <italic>p</italic> = 1.86 × 10−4) and COPD (rs11256442; <italic>p</italic> = 9.79 × 10−3) but with lower significance. Functional studies conducted on COPD patients showed that RNA expression of IL2RA, IFNγ and related proinflammatory cytokines in blood serum did not correlate with a specific genotype. Although results presented in this study do not fully support our hypothesis, it is worth to mention that the identified genes/SNPs that were associated with either COPD or LC risk, all were involved in the activation of the NF-κB transcription factor which is closely related to the regulation of the inflammatory response, a condition associated with both pathologies.
</abstract>

Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are closely related diseases associated with smoking history and dysregulated immune response. However, not all smokers develop the disease, indicating that genetic susceptibility could be important. Therefore, the aim of this study was to search for the potential overlapping genetic biomarkers, with a focus on single nucleotide polymorphisms (SNPs) located in the regulatory regions of immune-related genes. Additionally, the aim was to see if an identified SNP has potentially an effect on proinflamma-tory cytokine concentration in the serum of COPD patients. We extracted summary data of variants in 1511 immune-related genes from COPD and LC genome-wide association studies (GWAS) from the UK Biobank. The LC data had 203 cases, patients diagnosed with LC, and 360 938 controls, while COPD data had 1 897 cases and 359 297 controls. Assuming 1 association/gene, SNPs with a p-value < 3.3 × 10–5 were considered statistically significantly associated with the disease. We identified seven SNPs located in different genes (BAG6, BTNL2, TNF, HCP5, MICB, NCR3, ABCF1, TCF7L1) to be associated with the COPD risk and two with the LC risk (HLA-C, HLA-B), with statistical significance. We also identified two SNPs located in the IL2RA gene associated with LC (rs2386841; p = 1.86 × 10−4) and COPD (rs11256442; p = 9.79 × 10−3) but with lower significance. Functional studies conducted on COPD patients showed that RNA expression of IL2RA, IFNγ and related proinflammatory cytokines in blood serum did not correlate with a specific genotype. Although results presented in this study do not fully support our hypothesis, it is worth to mention that the identified genes/SNPs that were associated with either COPD or LC risk, all were involved in the activation of the NF-κB transcription factor which is closely related to the regulation of the inflammatory response, a condition associated with both pathologies.

Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer development

Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry

Clinical Department for Respiratory Diseases Jordanovac

University Hospital Zagreb, School of Medicine University of Zagreb

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are closely related diseases associated with smoking history and dysregulated immune...

Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer development

Published Online: Jun 12, 2023

Page range: 243 - 256

Accepted: Jan 09, 2023

DOI: https://doi.org/10.2478/acph-2023-0019

Keywords
GWAS, SNP, COPD, lung cancer, immune-related genes, NF-κB

© 2023 Jurica Baranasic et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer development

Published Online: Jun 12, 2023

Page range: 243 - 256

Accepted: Jan 09, 2023

DOI: https://doi.org/10.2478/acph-2023-0019

KeywordsGWAS, SNP, COPD, lung cancer, immune-related genes, NF-κB

© 2023 Jurica Baranasic et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
GWAS, SNP, COPD, lung cancer, immune-related genes, NF-κB