Yin Zhihua, Cui Zhigang, Ren Yangwu, Xia Lingzi, Wang Qianqian, Zhang Ying, He Qincheng, Zhou Baosen
Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, PR China; Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang 110122, PR China.
China Medical University, Shenyang 110122, PR China.
Lung Cancer. 2016 Apr;94:15-21. doi: 10.1016/j.lungcan.2016.01.013. Epub 2016 Jan 23.
MicroRNAs play important roles in the development of human chronic diseases including lung cancer. This is the first case-control study of lung cancer in a non-smoking female population in northeast China, to evaluate the roles of the polymorphisms in pre-miRNAs on risk of lung cancer.
The genotypes of six polymorphisms in miRNAs were determined in 575 patients with lung cancer and 608 healthy controls who were frequency matched for age.
For miR-146a rs2910164, individuals carrying heterozygous CG or homozygous GG genotype had decreased risks of lung cancer compared with those carrying homozygous wild CC genotype (adjusted odds ratios were 0.76 and 0.64, 95% confidence intervals were 0.59-0.99 and 0.46-0.90, P values were 0.039 and 0.010, respectively). G allele of rs2910164 was associated with a lower risk of lung cancer with a significant odds ratio of 0.80. MiR-423 rs6505162CA or AA genotype was associated with significantly decreased risk for lung cancer compared to CC genotype (adjusted odds ratios were 0.77 and 0.54). The significant result was also found in the allele model with odds ratio of 0.75. However, miR-196a2 rs11614913, miR-30c-1 rs928508, miR-608 rs4919510 and miR-27a rs895819 polymorphisms were not significantly associated with lung cancer risks in any models. The similar results were also found in lung adenocarcinoma patients.
These findings suggest that miR-146a rs2910164C>G and miR-423 rs6505162C>A polymorphisms may contribute to genetic susceptibility to lung cancer and lung adenocarcinoma in Chinese non-smoking females.
微小RNA在包括肺癌在内的人类慢性疾病发展过程中发挥着重要作用。这是中国东北地区非吸烟女性人群中首例肺癌病例对照研究，旨在评估前体微小RNA中的多态性对肺癌风险的作用。
在575例肺癌患者和608例年龄频率匹配的健康对照中，确定了微小RNA中6种多态性的基因型。
对于miR-146a rs2910164，与携带纯合野生型CC基因型的个体相比，携带杂合子CG或纯合子GG基因型的个体患肺癌的风险降低（调整后的比值比分别为0.76和0.64，95%置信区间分别为0.59-0.99和0.46-0.90，P值分别为0.039和0.010）。rs2910164的G等位基因与较低的肺癌风险相关，显著比值比为0.80。与CC基因型相比，miR-423 rs6505162的CA或AA基因型与肺癌风险显著降低相关（调整后的比值比分别为0.77和0.54）。在等位基因模型中也发现了显著结果，比值比为0.75。然而，在任何模型中，miR-196a2 rs11614913、miR-30c-1 rs928508、miR-608 rs4919510和miR-27a rs895819多态性均与肺癌风险无显著关联。在肺腺癌患者中也发现了类似结果。
这些发现表明，miR-146a rs2910164C>G和miR-423 rs6505162C>A多态性可能在中国非吸烟女性肺癌和肺腺癌的遗传易感性中起作用。
