1Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
2Hopp Children's Cancer Center (KiTZ) Heidelberg, Germany.
Acta Pharm. 2023 Jun 12;73(2):243-256. doi: 10.2478/acph-2023-0019. Print 2023 Jun 1.
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 -value < 3.3 × 10 were considered statistically significantly associated with the disease. We identified seven SNPs located in different genes () to be associated with the COPD risk and two with the LC risk (), with statistical significance. We also identified two SNPs located in the gene associated with LC (rs2386841; = 1.86 × 10) and COPD (rs11256442; = 9.79 × 10) 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.
慢性阻塞性肺疾病（COPD）和肺癌（LC）是密切相关的疾病，与吸烟史和失调的免疫反应有关。然而，并非所有吸烟者都会患上这种疾病，这表明遗传易感性可能很重要。因此，本研究旨在寻找潜在的重叠遗传生物标志物，重点是位于免疫相关基因调控区域的单核苷酸多态性（SNP）。此外，还旨在确定鉴定出的 SNP 是否对 COPD 患者血清中促炎细胞因子的浓度有潜在影响。我们从英国生物库中提取了 COPD 和 LC 全基因组关联研究（GWAS）中 1511 个免疫相关基因的变异汇总数据。LC 数据有 203 例病例，即被诊断为 LC 的患者，和 360938 例对照，而 COPD 数据有 1897 例病例和 359297 例对照。假设 1 个关联/基因，-值<3.3×10的 SNP 被认为与疾病有统计学显著关联。我们确定了七个位于不同基因中的 SNP（）与 COPD 风险相关，两个与 LC 风险相关（），具有统计学意义。我们还确定了两个位于基因中的 SNP 与 LC（rs2386841； = 1.86×10）和 COPD（rs11256442； = 9.79×10）相关，但显著性较低。对 COPD 患者进行的功能研究表明，血液中 IL2RA、IFNγ 和相关促炎细胞因子的 RNA 表达与特定基因型不相关。尽管本研究的结果不完全支持我们的假设，但值得一提的是，与 COPD 或 LC 风险相关的鉴定基因/SNP 都参与了 NF-κB 转录因子的激活，这与炎症反应的调节密切相关，这是两种疾病共有的条件。
