非小细胞肺癌中RARβ基因启动子甲基化与P53基因突变的相关性

[Correlation between RARbeta gene promoter methylation and P53 gene mutations in non-small cell lung cancer].

作者信息

Tan Cong, Jin Yong-tang, Xu He-yun, Zhang Chen-ye, Zhang Hu, Zhang Wei-min, Chen Chun-mei, Sun Xiao-yu

机构信息

Department of Environmental Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.

出版信息

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012 Apr;29(2):131-6. doi: 10.3760/cma.j.issn.1003-9406.2012.02.003.

DOI:10.3760/cma.j.issn.1003-9406.2012.02.003

PMID:22487818

Abstract

OBJECTIVE

To investigate the correlation between RARbeta gene promoter methylation and P53 gene mutations in non-small cell lung cancer (NSCLC).

METHODS

Promoter methylation of RARbeta and P53 mutations of exons 5 through 9 in 198 resected primary NSCLC tissues were determined by methylation-specific PCR and direct sequencing.

RESULTS

RARbeta gene promoter methylation and P53 mutation were detected in 58.1% and 36.4% of tumors, respectively. Both were higher in males than in females and in smokers than in nonsmokers. A higher prevalence of RARbeta promoter methylation was found in patients with advanced stage tumors than those with TNM stage I. P53 gene mutations were more frequent in squamous cell carcinoma and adeno-squamous carcinoma than adenocarcinoma. All such differences were statistically significant (P< 0.05). Frequencies of P53 mutations, including G:C>T:A mutations, transversions and missense mutations were significantly higher in tumors with RARbeta methylation than in those without (P< 0.05). A significantly higher prevalence of RARbeta methylation was found in tumors with only G:C>T:A mutation in P53 gene than those without P53 mutations (P< 0.05). This difference (OR=3.737, 95%CI: 1.414-9.873) was still statistically significant (P< 0.05) in smokers (OR=4.020, 95%CI: 1.263-12.800), squamous cell carcinomas (OR=5.480, 95%CI: 1.400-21.446) or patients with advanced tumors (OR=3.446, 95%CI: 1.054-11.267) after adjusting for age and sex.

CONCLUSION

RARbeta methylation is associated with G:C>T:A mutations in P53 gene in NSCLC.

摘要

目的

探讨非小细胞肺癌（NSCLC）中RARβ基因启动子甲基化与P53基因突变之间的相关性。

方法

采用甲基化特异性PCR和直接测序法，检测198例手术切除的原发性NSCLC组织中RARβ启动子甲基化及外显子5至9的P53突变情况。

结果

肿瘤中RARβ基因启动子甲基化和P53突变的检出率分别为58.1%和36.4%。男性和吸烟者中的两者检出率均高于女性和不吸烟者。晚期肿瘤患者中RARβ启动子甲基化的发生率高于TNM I期患者。P53基因突变在鳞状细胞癌和腺鳞癌中比腺癌更常见。所有这些差异均具有统计学意义（P<0.05）。RARβ甲基化的肿瘤中P53突变的频率，包括G:C>T:A突变、颠换和错义突变，均显著高于无RARβ甲基化的肿瘤（P<0.05）。P53基因仅发生G:C>T:A突变的肿瘤中RARβ甲基化的发生率显著高于无P53突变的肿瘤（P<0.05）。在调整年龄和性别后，吸烟者（OR=4.020，95%CI：1.263-12.800）、鳞状细胞癌（OR=5.480，95%CI：1.400-21.446）或晚期肿瘤患者（OR=3.446，95%CI：1.054-11.267）中的这种差异（OR=3.737，95%CI：1.414-9.873）仍具有统计学意义（P<0.05）。