肺癌是严重威胁人类健康的公共卫生问题。NER系统基因的单核苷酸多态性 (SNP) 以及非编码RNA (miRNAs) 表观遗传调控和肿瘤遗传易感的关联研究颇受关注。前期研究发现，海南汉族人群中，NER系统基因多态及单体型可增加肺癌的发病风险。XPB、XPD、XPG基因3′UTR的SNP可能干扰miRNAs功能而异常调控靶基因表达水平，从而影响肺癌的遗传易感性，值得进一步探讨。另外，我们还需关注海南地区少数民族黎族人群。因此，本项目拟选择海南地区肺癌人群为研究对象，采用病例对照研究方法，检测XPD rs3916843 (A>G)，XPG rs873601 (G>A) 基因多态，分析其与肺癌患者发病风险的关联。采用microRNA芯片技术检测五个miRNA表达水平。构建候选miRNA-SNP转染细胞模型，与人群研究结果相结合，得到肺癌遗传易感关联的NER系统基因miRNA-SNPs。

Lung cancer is a complex process involved in genes and other factors, and its occurrence and development resulted from genetic and environmental interaction. Nucleotide excision repair (NER) is an important defense mechanism of the body to exogenous carcinogens and mutagens, such as benzo[a]pyrene (B[a]P). Research shows that DNA repair ability is the important factor to cancer susceptibility and DNA repair ability is closely related with single nucleotide polymorphisms (SNPs) and MicroRNAs (miRNAs). SNPs are the most abundant form of DNA variation in the human genome. A miRNA can bind to the 3’ untranslated region (UTR) of its target mRNA to post-transcriptionally regulate genes. Studies have shown that miRNAs play a role in several biological processes, including embryonic development, cell proliferation and differentiation, apoptosis, fat metabolism, atherosclerosis and oncogenesis. SNPs within the binding site of miRNA can affect miRNA-induced genetic repression. If an SNP can influence the binding of a miRNA to its target gene, this SNP is called a miRNA-SNP. Therefore, miRNA-SNPs can affect gene expression levels to influence susceptibility to disease. In the present study, we found that XPB and XPG are associated with the risk of lung cancer in Hainan. In addition, we will consider the genetic susceptibility of lung cancer in Li population. Therefore, we aim to identify miRNA-SNPs in the genes of NER pathways that may influence risk of lung cancer in Hainan. The combination of population investigations and functional studies related to miRNA-SNPs will provide powerful approaches for molecular epidemiological association studies in predicting lung cancer risk.