DNA修复基因O~6-甲基鸟嘌呤-DNA甲基转移酶在人群肺癌发生中的作用

吕嘉春; 施侣元; 吴中亮; 廖永德; 周晟; 王孝养; 黎银燕; 宾晓农; 曾波航; 陈家堃

Abstract

吕嘉春,施侣元,吴中亮,廖永德,周晟,王孝养,黎银燕,宾晓农,曾波航,陈家堃.DNA修复基因O~6-甲基鸟嘌呤-DNA甲基转移酶在人群肺癌发生中的作用[J].Chinese journal of Epidemiology,2003,24(1):40-44

DNA修复基因O~6-甲基鸟嘌呤-DNA甲基转移酶在人群肺癌发生中的作用

A study on the role of DNA repair gene O6-methylguanine-DNA methyltransferase in the development of human lung cancer

Received:November 20, 2001

DOI：

KeyWord: DNA修复 O⁶-甲基鸟嘌呤-DNA甲基转移酶肺肿瘤

English Key Word: DNA repair O⁶-methylg uanine-DNA methyltransferase Lung neoplasms

FundProject:国家自然科学基金资助项目 ( 30200235 );广东省重点科技攻关资助项目 ( 2002B30104、97001);广东省医学科研资助项目(B2001075 )

Author Name	Affiliation
Lu Jia-chun	The Institute for Chemical Carcinogenesis, Guangzhou Medical College, Guangzhou 510182, China
Shi Lu-yuan	华中科技大学同济医学院流行病学与卫生统计学系, 上海 200000
Wu Zhong-liang	The Institute for Chemical Carcinogenesis, Guangzhou Medical College, Guangzhou 510182, China
Liao Yong-de	同济医学院附属同济医院, 上海 200000
Zhou Sheng	同济医学院附属同济医院, 上海 200000
Wang Xiao-yang	同济医学院附属同济医院, 上海 200000
Li Yin-yan	广州医学院细胞生物学与医学遗传学教研室, 广州, 510182
Bin Xiao-nong	The Institute for Chemical Carcinogenesis, Guangzhou Medical College, Guangzhou 510182, China
Zeng Bo-hang	广州医学院附属医院肿瘤科, 广州 510182
Chen Jia-kun	The Institute for Chemical Carcinogenesis, Guangzhou Medical College, Guangzhou 510182, China

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Abstract:

目的: 探讨DNA修复基因O⁶甲基鸟嘌呤DNA甲基转移酶(O⁶ methylguanine DNAmethyltransferase, hMGMT)在人群肺癌发生中的作用。方法: 用逆转录聚合酶链反应 (RT PCR)技术检测 150例肺癌组织、40例正常肺组织、50对肺癌病例和对照外周血单个核细胞中hMGMT基因mRNA的表达; 用免疫组化检测p53、CMYC、KRAS基因表达; 并分析有关暴露因素对修复基因hMGMT表达的影响, 以及hMGMT基因与 p53、CMYC、K RAS等癌变相关基因的关系。结果: 32.7% (49/150)的肺癌组织和5.0% (2/40)的正常肺组织存在hMGMT基因表达低下, hMGMT基因表达低下与肺癌发生的危险度OR值为9.22 (2.05～ 57.65 )。 20.0% (10/50)的肺癌病人外周血和4% (2/50)的正常人外周单个核细胞血细胞也可检出hMGMT基因表达低下。探讨影响hMGMT基因表达的各种暴露因素 ,发现吸烟可抑制hMGMT基因表达。另外发现, K RAS癌基因的过度表达与hMGMT表达低下有关 (P<0.05 ); 而 p53、CMYC基因的表达与hMGMT无关。结论: DNA修复基因hMGMT可能在肺癌发生中起着重要的作用, 其表达低下是人群发生肺癌的危险因素之一, 该基因的低表达可作为有价值的肺癌易感性标志。

English Abstract:

Objective: To study the role of O⁶-methy lguanine-DNA me thyltransferase (hMGMT) in the development of human lung cancer. Methods: Reverse transcription-polymerase chain reaction (RTPCR) method was applied to measure hMGMT mRNA expression in 150 lung cancer specimens, 40 normal lung tissues, and in the peripheral mononuclear blood cells from 50 lung cancer cases and 50 normal controls. The protein expressions of p53, C-MYC and K-RAS were assessed by immuno-histochemistry. The effects of some exposure factors on the expression of hMGMT gene were analyzed. The relationships between hMGMT gene and cancer related genes p53, C-MYC and K-RAS were investigated. Results: The mRNA of hMGM T was low or absent in 49 of 150(32.7%)lung cancer specimens, whereas 2 of 40 (5%) normal lung tissues had reduced the levels of hMGM T mRNA. The low expression of hMGM T seemed to be a risk factor of lung cancer, with a OR of 9.22(2.05-57.65). Reduced expression levels of hMGM T mRNA were observed in 10 of 50 (20%) lung cancer patients' peripheral mononuclear blood cells, and 2 of 50 (4%)blood cells among normal controls. When investigating the exposure factors which affecting the expression of hMGMT gene, we noticed that smoking was suppressing the expression of hMGM T gene. I nterestingly, over-expression of K-RAS oncogene was significantly cor related with low expression of hMGMT (P<0.05). However, the expressions of p53 and C-myc were not correla ted with the status of hMGMT gene. Conclusion:　hMGMT might play an important role in the development of human lung cancer. Low expression of hMGMT gene seemed to be a risk factor for lung cancer which could be used as a valuable biomarker on susceptibility of human lung cancers.

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