Abstract
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, p = 0.012) and CC genotype (OR = 2.93, 95% CI = 1.07–7.9, p = 0.034, 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, p = 0.048) and the A allele frequency (OR = 0.58, 95% CI = 0.35–0.98, p = 0.043) 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, p = 0.024). 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.
Highlights
Lung cancer is the most common cancer worldwide and is associated with high mortality rates [1]. e two main subtypes of lung cancer are small-cell (SCLC) and non-small-cell lung carcinoma (NSCLC)
NSCLC encompasses over 80–85% of lung cancers SCLC, which accounts for 12% of all cases, is more aggressive than NSCLC [1]
Results e study included 165 NSCLC cases and 147 healthy controls (Table 1) with a mean age of 58.5 and 52.6 years in cases and controls, respectively. e age and gender distributions were similar between the two groups (p > 0.05). e distribution of the rs2910164 and rs767649 genotypes in the control group by Hardy–Weinberg equilibrium (HWE) was (X2 1.57, p value 0.209 and X2 1.85, p value 0.173, respectively), which indicates the randomness of the control samples
Summary
Lung cancer is the most common cancer worldwide and is associated with high mortality rates [1]. e two main subtypes of lung cancer are small-cell (SCLC) and non-small-cell lung carcinoma (NSCLC). In spite of the considerable improvement in diagnosis and treatment, lung cancer remains the leading cause of cancer-related deaths globally [2]. Smoking is one of the major risk factors for lung cancer, nonsmokers suffer from the disease [3]. Previous studies on the SNPs Rs2910164 in miR-146a and Rs767649 in miR-155 showed association with non-small cell lung cancer (NSCLC) development. Us, the aim of this study was to detect any correlation between those SNPs in Iranian NSCLC patients. 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. When patients were stratified according to smoking exposure, no association with rs2910164 variants was found
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