Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Medicine (Baltimore). 2021 Mar 26;100(12):e23716. doi: 10.1097/MD.0000000000023716.
Lung cancer is the leading cause of cancer-associated mortality worldwide. Genetic factors are reported to play important roles in lung carcinogenesis. To evaluate genetic susceptibility, we conducted a hospital-based case-control study on the effects of functional single nucleotide polymorphisms (SNPs) in long non-coding RNAs (lncRNAs) and microRNAs on lung cancer development. A total of 917 lung cancer cases and 925 control subjects were recruited. The MALAT1 rs619586 A/G genotype frequencies between patient and control groups were significantly different (P < .001), specifically, 83.85% vs 75.88% (AA), 15.60% vs 21.79% (AG), and 0.55% vs 2.32% (GG). When the homozygous genotype MALAT1 rs619586 AA was used as the reference group, AG (AG vs AA: adjusted odds ratio [OR] 0.65, 95% confidential interval [CI] 0.51-0.83, P = .001) and GG genotypes were associated with significantly decreased risk of lung cancer (GG vs AA: adjusted OR 0.22, 95% CI 0.08-0.59, P = .003). In the dominant model, MALAT1 rs619586 AG/GG variants were also associated with a significantly decreased risk of lung cancer (adjusted OR 0.61, 95% CI 0.48-0.78, P < .001). In the recessive model, when MALAT1 rs619586 AA/AG genotypes were used as the reference group, the GG homozygous genotype was also associated with significantly decreased risk for lung cancer (adjusted OR 0.24, 95% CI 0.09-0.64, P = .004). Hsa-miR-34b/c rs4938723 T > C, pri-miR-124-1 rs531564 C > G and hsa-miR-423 rs6505162 C > A SNPs were not associated with lung cancer risk. Our collective data indicated that MALAT1 rs619586 A/G SNPs significantly reduced the risk of lung cancer. Large-scale studies on different ethnic populations and tissue-specific biological characterization are required to validate the current findings.
肺癌是全球癌症相关死亡的主要原因。遗传因素被认为在肺癌发生中起重要作用。为了评估遗传易感性,我们进行了一项基于医院的病例对照研究,探讨长非编码 RNA(lncRNA)和 microRNA 中功能性单核苷酸多态性(SNP)对肺癌发展的影响。共纳入 917 例肺癌病例和 925 例对照。病例组和对照组 MALAT1 rs619586 A/G 基因型频率差异有统计学意义(P<0.001),具体为 83.85%比 75.88%(AA)、15.60%比 21.79%(AG)和 0.55%比 2.32%(GG)。当 MALAT1 rs619586 AA 纯合基因型用作参考组时,AG(AG 与 AA:调整后的优势比[OR]0.65,95%置信区间[CI]0.51-0.83,P=0.001)和 GG 基因型与肺癌风险显著降低相关(GG 与 AA:调整后的 OR 0.22,95%CI0.08-0.59,P=0.003)。在显性模型中,MALAT1 rs619586 AG/GG 变异也与肺癌风险显著降低相关(调整后的 OR 0.61,95%CI0.48-0.78,P<0.001)。在隐性模型中,当 MALAT1 rs619586 AA/AG 基因型用作参考组时,GG 纯合基因型也与肺癌风险显著降低相关(调整后的 OR 0.24,95%CI0.09-0.64,P=0.004)。Hsa-miR-34b/c rs4938723 T>G、pri-miR-124-1 rs531564 C>G 和 hsa-miR-423 rs6505162 C>A SNP 与肺癌风险无关。我们的综合数据表明,MALAT1 rs619586 A>G SNP 显著降低了肺癌风险。需要在不同种族人群中进行大规模研究,并进行组织特异性生物学特征验证,以验证当前的发现。