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CYP1A1和GSTM1基因多态性与内蒙古人群肺癌易感性的关系 被引量:11

Relationship between CYP1A1 and GSTM1 genetic polymorphisms and lung cancer susceptibility in population of Inner Mongolia
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摘要 背景与目的 肺癌是严重危害人类健康的恶性肿瘤之一,其发病与肺癌人群中某些肺癌相关基因的遗传多态性有关。本研究旨在探讨细胞色素P4501A1(CYP1A1)基因多态性和谷胱甘肽硫转移酶M1(GSTM1)基因多态性与内蒙古人群肺癌易感性的关系。方法 用PCR-RFLP技术分析了原发性肺癌组和住院对照组(各163例)的CYP1A1、GSTM1基因的多态性、基因型分布频率和交互作用。结果 CYP1A1突变型和GSTM1基因缺陷型EGSTM1(-)]频率分布分别为36.8%、65.0%(病例组)和19.0%、48.9%(对照组),二者经χ^2检验差异有显著性(χ^2=12.82,P=0.000;χ^2=9.78,P=0.002)。CYP1A1突变型患肺癌的风险显著增加(OR=2.48,95%CI为1.51~4.08)。GSTM1(-)者患肺癌的风险也显著增加(OR=2.03,95%CI为1.30~3.17)。基因突变的协同分析发现CYP1A1突变型/GSTM1(-)在肺癌组和对照组中的分布频率分别为28.8%和8.0%,二者经χ^2检验有显著性差异(χ^2=23.883,P=0.000)。CYP1A1突变型/GSTM1(-)患肺癌的风险显著增加(OR=4.90,95%CI为2.50~9.83)。无论是在肺癌组还是在对照组,CYP1A1突变型/GSTM1(-)和CYP1A1非突变型/GSTM1(-)在性别间分布频率的差异均无显著性(肺癌组χ^2=0.797,P=0.372;对照组χ^2=0.670,P=0.761)。吸烟与肺癌易感性的统计学分析,结果显示吸烟与肺癌易感性有关(χ^2=14.197,P=0.000),吸烟者患肺癌的风险显著增加(OR=2.33,95%CI为1.50~3.62)。CYP1A1突变型与吸烟关系的协同分析发现,携带CYP1A1突变型基因的吸烟者较携带CYP1A1突变型基因不吸烟者易患肺癌(OR=4.44,95%CI为2.40~8.32,χ^2=23.843,P=0.000)。GSTM1(-)与吸烟关系的协同分析中也发现,携带GSTM1(-)的吸烟者患肺癌的风险显著增加(OR=7.32,95%CI为3.39~15.50,χ^2=36.708,P=0.000)。结论 CYP1A1突变型和GSTM1(-)是内蒙古地区肺癌的易患因素,二者对肺癌的发生有协同作用,吸烟与肺癌的易感性也有关,CYP1A1突变型、GSTM1(-)与吸烟在肺癌的发生上也有相互促进作用。 Background and objective Lung cancer is one of malignant tumors to hurt human health. It has been known that the development of lung cancer may be associated with genetic polymorphism of some lung cancer related genes. The aim of this study is to explore the susceptibility to lung cancer in relation to CYP1A1 and GSTM1 genetic polymorphisms in population of Inner Mongolia. Methods CYP1A1 and GSTM1 genetic polymorphisms were determined by PCR-RFLP in 163 lung cancer cases and healthy controls respectively. Results The frequencies of CYP1A1 variation genotype (vt/vt) and GSTM1(-) were 36. 8% and 65.0% in lung cancer cases and 19.0% and 48.9% in healthy controls respectively. Statistical tests showed significant difference in the frequencies between the two groups (χ^2=12.82, P=0.0001; χ^2= 9.78, P=0.002). The risk of lung cancer with CYP1A1 variation genotype was significantly higher than those of controls (OR= 2.48, 95% CI=1. 51-4. 08). The individuals who carried with GSTMI-null genotype had a high risk of lung cancer (OR=2.03, 95% CI=1.30 3. 17). Combined analysis of the polymorphisms showed that percentage of CYP1A1(vt/vt)/GSTM1(- ) in lung cancer and control groups was 28.8% and 8.0% respectively (χ^2 = 23. 883. P=0.0001). The people who carried with CYP1A1(vt/vt)/GSTM1(-) had a high risk of lung cancer (OR=4.90. 95% CI=2.50 9.83). PearsonChi Square of sex differential showed there was no significance between the homozygous variation genotype of CYP1A1/GSTM1 (-) and the other genotypes of CYP1A1/GSTM1(-) neither in lung cancer group (χ^2 =0. 797, P=0. 372) nor in control group (χ^2 =0. 670. P=0.761). Statistical tests showed that susceptibility to lung cancer was related to smoking (χ^2= 14. 197, P =0.000), the risk of lung cancer in smoking individuals raised remarkably (OR=2. 33. 95% CI= 1. 50 3.62). There may bea synergeticinteraction betweenCYP1A1 variationgenotype (vt/vt) and smoking on the elevated susceptibility to lung cancer (χ^2= 23.843, P=0.000), the smokers who carried with CYP1A1 (vt/ vt) had a significantly higher risk of lung cancer (OR=4. 44, 95% CI=2. 40 8. 32, χ^2 = 23. 813. P= 0.000). So did the GSTM1(-) and smoking on the elevated susceptibility to lung cancer, the significantly higher risk of lung cancer had also been found in those smokers who carried with (ISTM1(-) (OR=7.32, 95%CI=3. 39-15. 50, χ^2= 36. 708,P=0. 000). Conclusion The polymorphisms of CYP1A1 vt/vt and GSTM1(-) are the risk factors in lung cancer of Inner Mongolia. Smoking is also related to the susceptibility to lung cancer. There may be a synergetic interaction between CYP1A1 (vt/vt) and GSTM1(-) on the ele rated susceptibility of lung cancer. So do the CYP1A1 (vt/vt), GSTM1(-) and smoking.
出处 《中国肺癌杂志》 CAS 2006年第5期413-417,共5页 Chinese Journal of Lung Cancer
基金 内蒙古教育厅科学研究基金(NJ03128)资助~~
关键词 CYP1A1 GSTM1 肺肿瘤 基因多态性 CYP1A1 GSTM1 Lung neoplasms Genetic potymorphism
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参考文献10

  • 1Nakachi K, lmai K, Hayashi S, et al. Genetic susceptibility to squamous cell carcinoma of the lung in relation to cigarette smokingdose. Cancer Res,1991,51(19) : 5177-5180.
  • 2胡毅玲,高杨,张桥.细胞色素P450 1A1、2D6和谷胱甘肽硫转移酶基因多态性与肺癌易感性的研究[J].肿瘤,1998,18(4):269-271. 被引量:25
  • 3吴翠玲,陈思东,林广平,曾勉,汪保国,陈漫霞,蔡旭玲.CYP1A1和GSTM1基因多态与肺癌发病关系的病例-对照研究[J].华南预防医学,2003,29(4):13-16. 被引量:5
  • 4Hayashi S, Watanabc J, Nakachi K, el al. Genetic linkage of lung cancer associated Msp Ⅰ polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P4501A1 gene. J Biochem (Tokyo),1991,110(3) : 407-411.
  • 5Belogubova EV, Ulibina YM, Suvorova IK, et al. Combined CYP1A1/GSTM1 at risk genotypes are overrepresenled in squamous cell lung carcinoma patients but underrepresented in elderly tumor-free subjects. J Cancer Res Clin Oncol,2006,132(5):327-331.
  • 6Sobti RC, Sharma S, Joshi A, et al. Genetic polymorphism of the CYP1A1, CYP2E1. GSTM1 and GSTTI genes and lung cancer susceptibility in a north indian population. Mol Cell Biochem.2004,266(1-2):1-9.
  • 7Ng DP, Tan KW. Zhao B. et al. CYP1A1 polymorphisms and risk of lung cancer in non-smoking Chinese women: influence of environmental tobacco smoke exposure and GSTM1/T1 genetic variation. Cancer Causes Control,2005,16(1) : 399-405.
  • 8Sreeja L, Syamala V, Hariharan S, et al. Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South Indian population. J Hum Genet.2005,50(12):618-627.
  • 9Song N, Tan W, Xing D, et al.CYP 1A1 polymorphism and risk of lung cancer in relation to tobacco smoking:a case control study in China. Carcinogenesis,2001,22(1) : 11-16.
  • 10李代蓉,周清华,袁天柱,郭占林,朱文,王艳萍,陈晓禾,冯志华,车国卫.GSTM1和CYP2E1基因多态性与肺癌遗传易感性关系的研究[J].中国肺癌杂志,2005,8(1):14-19. 被引量:17

二级参考文献24

  • 1汪保国,陈思东,陈阳,周卫平,曾勉,李志彪.细胞色素P4502E1和1A1多态性与肺癌关系的病例对照研究[J].肿瘤防治杂志,2004,11(7):681-684. 被引量:6
  • 2皮静波,孙贵范,吕秀强,陆春伟,郑全美.细胞色素P450IA1高诱导基因型与肺癌易感性关系的研究[J].中华结核和呼吸杂志,1996,19(1):33-36. 被引量:12
  • 3李连弟,鲁凤珠,张思维,牧人,孙秀娣,皇甫小梅,孙杰,周有尚,欧阳宁慧,饶克勤,陈育德,孙爱明,薛志福,夏毅.中国恶性肿瘤死亡率20年变化趋势和近期预测分析[J].中华肿瘤杂志,1997,19(1):3-9. 被引量:868
  • 4[8]Arholm M. Purification of a glutathione S-transferase from human liver having high activity with benzo(a) pyrene-4, 5-oxide. Biochem Biophys Res Comm, 1981,98:512- 519.
  • 5[9]Seidegard J, Pero RW, Markowitz MM, et al. Isoenzyme (s) of glutathione trancsferase (class Mu) as a marker for the susceptibility to lung cancer: a follow up study. Carcinogenesis, 1990,11: 33 - 36.
  • 6Bartsch H, Nair U, Risch A, et al. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol Biomarkers Prey, 2000,9 (1): 3-28.
  • 7Taningher M, Malacarne D, Izzotti A, et al. Drug metabolism polymorphisms as modulators of cancer susceptibility. Mutat Res,1999,436(3): 227-261.
  • 8Hayashi S, Watanabe J, Kawajiri K. Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450 Ⅱ E1 gene. J Biochem (Tokyo), 1991,110(4) : 559-565.
  • 9Marchand LL, Wilkinson GR, Wilkens LR. Genetic and dietary predictors of CYP2E1 activity: a pbenotyping study in Hawaii Japanese using chlorzoxazone. Cancer Epidemiol Biomarkers Prev,1999,8(6): 495 500.
  • 10Kato S, Shields PG, Caporaso NE, et al. Cytochrome P450 Ⅱ E1genetic polymorphisms, racial variation, and lung cancer risk.Cancer Res,1992,52(23): 6712-6715.

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