Acta Pharmaceutica, Vol. 73 No. 2, 2023.
Original scientific paper
https://doi.org/10.2478/acph-2023-0019
Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer development
JURICA BARANASIC
orcid.org/0000-0001-9971-9733
; Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia
YASMEEN NIAZI
; Hopp Children’s Cancer Center (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany
SUBHAYAN CHATTOPADHYAY
; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany; Departments of Clinical Genetics, Lund University, Lund, Sweden
LADA RUMORA
orcid.org/0000-0002-5302-3770
; Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia
LORNA ĆORAK
; Clinical Department for Respiratory Diseases Jordanovac, University Hospital Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia
ANDREA VUKIĆ DUGAC
orcid.org/0000-0002-1522-3325
; Clinical Department for Respiratory Diseases Jordanovac, University Hospital Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia
MARKO JAKOPOVIĆ
orcid.org/0000-0002-4815-7512
; Clinical Department for Respiratory Diseases Jordanovac, University Hospital Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia
MIROSLAV SAMARŽIJA
; Clinical Department for Respiratory Diseases Jordanovac, University Hospital Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia
ASTA FÖRSTI
orcid.org/0000-0002-9857-4728
; Hopp Children’s Cancer Center (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany
JELENA KNEŽEVIC
orcid.org/0000-0002-3152-3563
; Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia; Faculties of Dental Medicine and Health, University of Osijek, Osijek, Croatia
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 proinflammatory 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.
Keywords
GWAS; SNP; COPD; lung cancer; immune-related genes; NF-κB
Hrčak ID:
303173
URI
Publication date:
30.6.2023.
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