Aberrant promoter methylation of hOGG1 may be associated with increased risk of non-small cell lung cancer.
Aberrant promoter methylation of hOGG1 may be associated with increased risk of non-small cell lung cancer.
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DOI：
10.18632/oncotarget.14177
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发表时间：
2017-01-31
期刊：
影响因子：
--
通讯作者：
Liu Z
中科院分区：
文献类型：
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作者：
Qin H;Zhu J;Zeng Y;Du W;Shen D;Lei Z;Qian Q;Huang JA;Liu Z
DNA甲基化可能在非小细胞肺癌的表观遗传学上改变肿瘤抑制基因。由于人8-氧代鸟嘌呤DNA糖基化酶（hOGG 1）基因启动子在NSCLC中频繁甲基化，我们评估了hOGG 1的遗传或表观遗传改变是否与非小细胞肺癌风险增加相关。在217例NSCLC患者和226例健康对照的病例对照研究中，采用PCR-限制性片段长度多态性分析对3个hOGG 1单倍型标记SNP（htSNP）进行基因分型，采用PCR-单链构象多态性分析对1个htSNP进行基因分型。通过甲基化特异性PCR检测121例NSCLC患者和121例对照外周血单个核细胞标本中hOGG 1的甲基化谱。在四个多态位点（rs 159153、rs 125701、rs 1052133和rs 293795）中的任何一个位点上，NSCLC患者和对照组之间的等位基因或基因型频率均无差异。然而，hOGG 1甲基化阳性携带者发生NSCLC的风险是无甲基化受试者的2.25倍（校正比值比：2.247; 95%置信区间：1.067-4.734; P = 0.03）。此外，去甲基化剂5-氮杂-2 '-脱氧胞苷恢复了NSCLC细胞系中hOGG 1的表达。这些数据为中国人群外周血单核细胞hOGG 1甲基化与NSCLC风险之间的相关性提供了强有力的证据。
DNA methylation may epigenetically inactivate tumor suppressor genes in NSCLC. As the human 8-oxoguanine DNA glycosylase (hOGG1) gene promoter is frequently methylated in NSCLC, we evaluated whether genetic or epigenetic alterations of hOGG1 are associated with increased risk of non-small cell lung cancer. Three hOGG1 haplotype-tagging SNPs (htSNP) were genotyped in PCR-restriction fragment length polymorphism assays, and one htSNP was genotyped in a PCR-single-strand conformation polymorphism assay in case-control studies of 217 NSCLC patients and 226 healthy controls. The methylation profiles of peripheral blood mononuclear cell specimens from 121 NSCLC patients and 121 controls were determined through methylation-specific PCR of hOGG1. No differences in allele or genotype frequencies between NSCLC patients and controls were observed at any of the four polymorphic sites (rs159153, rs125701, rs1052133, and rs293795). However, hOGG1 methylation-positive carriers had a 2.25-fold greater risk of developing NSCLC (adjusted odds ratio: 2.247; 95% confidence interval: 1.067-4.734; P = 0.03) than methylation-free subjects. Furthermore, the demethylating agent 5-aza-2’-deoxycytidine restored hOGG1 expression in NSCLC cell lines. These data provide strong evidence of an association between peripheral blood mononuclear cell hOGG1 methylation and the risk of NSCLC in a Chinese population.