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  • Baranasic, JuricaRuder Boskovic Institute (author)

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

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023
  • 14 s.

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  • LIBRIS-ID:oai:lup.lub.lu.se:3f18e77a-2041-467b-a4fb-2e969648b063
  • https://lup.lub.lu.se/record/3f18e77a-2041-467b-a4fb-2e969648b063URI
  • https://doi.org/10.2478/acph-2023-0019DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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, IFNγand 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.

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  • Niazi, YasmeenHopp Children’s Cancer Center Heidelberg (KiTZ),German Cancer Research Centre (author)
  • Chattopadhyay, SubhayanLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,German Cancer Research Centre(Swepub:lu)su1252ch (author)
  • Rumora, LadaUniversity of Zagreb (author)
  • Ćorak, LornaUniversity Hospital Centre Zagreb (author)
  • Dugac, Andrea VukićUniversity Hospital Centre Zagreb (author)
  • Jakopović, MarkoUniversity Hospital Centre Zagreb (author)
  • Samaržija, MiroslavUniversity Hospital Centre Zagreb (author)
  • Försti, AstaHopp Children’s Cancer Center Heidelberg (KiTZ)(Swepub:lu)med-asf (author)
  • Knežević, JelenaRuder Boskovic Institute,University of Osijek (author)
  • Ruder Boskovic InstituteHopp Children’s Cancer Center Heidelberg (KiTZ) (creator_code:org_t)

Related titles

  • In:Acta Pharmaceutica73:2, s. 243-2561330-0075

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