Background. Lung cancer is one of the leading causes of death worldwide. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and may act as both tumor suppressors and as oncogenes. The presence of single nucleotide polymorphisms (SNPs) inside the miRNA genomic region could affect target miRNA maturation, expression, and binding to its target mRNA and contribute to cancer development. Previous studies on the SNPs Rs2910164 in miR-146a and Rs767649 in miR-155 showed association with non-small cell lung cancer (NSCLC) development. Thus, the aim of this study was to detect any correlation between those SNPs in Iranian NSCLC patients. Methods. In a small cohort study, 165 NSCLC patients and 147 noncancer controls were enrolled between Apr 2015 and Sep 2019 at the Masih Daneshvari Hospital, Tehran, Iran. Allele frequencies from the genomic DNA of blood cells were studied using PCR-RFLP and their association with the risk of lung cancer was evaluated. Results. The rs2910164C allele (OR = 1.56, 95% CI = 1.10–2.21, ) and CC genotype (OR = 2.93, 95% CI = 1.07–7.9, , respectively) were associated with a significantly increased risk for lung cancer compared to that for the GG genotype. When patients were stratified according to smoking exposure, no association with rs2910164 variants was found. The AT genotype (OR = 0.57, 95% CI = 0.33–0.99, ) and the A allele frequency (OR = 0.58, 95% CI = 0.35–0.98, ) in rs767649 were lower in NSCLC patients in comparison with the control group. In addition, the rs767649 AT genotype frequency in smoking controls was higher than in smoking NSCLC patients (OR = 0.44, 95% CI = 0.21–0.90, ). No association was found between rs2910164 and rs767649 variants and stage or type of NSCLC. Conclusion. Our finding suggests that miR-146a rs2910164 and miR-155 rs767649 polymorphisms may be considered as genetic risk factors for the susceptibility to NSCLC in the Iranian population. However, a larger multicenter study across Iran is needed to confirm these findings.

中文翻译：

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miR-146a SNP Rs2910164 和 miR-155 SNP rs767649 是伊朗人群中非小细胞肺癌的危险因素

背景。肺癌是世界范围内导致死亡的主要原因之一。MicroRNA (miRNA) 是调节基因表达的小型非编码 RNA，可以作为肿瘤抑制基因和致癌基因。miRNA 基因组区域内单核苷酸多态性 (SNP) 的存在可能会影响目标 miRNA 的成熟、表达和与其目标 mRNA 的结合，并有助于癌症的发展。先前对 miR-146a 中的 SNP Rs2910164 和 miR-155 中的 Rs767649 的研究表明与非小细胞肺癌 (NSCLC) 的发展有关。因此，本研究的目的是检测伊朗 NSCLC 患者中这些 SNP 之间的任何相关性。方法. 在一项小型队列研究中，2015 年 4 月至 2019 年 9 月期间，在伊朗德黑兰的 Masih Daneshvari 医院招募了 165 名 NSCLC 患者和 147 名非癌症对照者。使用 PCR-RFLP 研究了血细胞基因组 DNA 的等位基因频率，并评估了它们与肺癌风险的关联。结果。rs2910164C 等位基因（OR = 1.56，95% CI = 1.10–2.21，)和 CC 基因型 (OR = 2.93, 95% CI = 1.07–7.9,，分别）与 GG 基因型相比，肺癌风险显着增加。当根据吸烟暴露对患者进行分层时，未发现与 rs2910164 变异相关。AT 基因型 (OR = 0.57, 95% CI = 0.33–0.99,)和 A 等位基因频率 (OR = 0.58, 95% CI = 0.35–0.98,) rs767649 在 NSCLC 患者中低于对照组。此外，吸烟对照组的 rs767649 AT 基因型频率高于吸烟的 NSCLC 患者（OR = 0.44，95% CI = 0.21–0.90，）。rs2910164 和 rs767649 变异与 NSCLC 的分期或类型之间没有发现关联。结论。我们的发现表明 miR-146a rs2910164 和 miR-155 rs767649 多态性可能被认为是伊朗人群中 NSCLC 易感性的遗传风险因素。然而，需要在伊朗进行更大规模的多中心研究来证实这些发现。