Role of glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes in modulating susceptibility to smoking-related lung cancer
Role of glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes in modulating susceptibility to smoking-related lung cancer
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DOI：
10.1097/00008571-199812000-00006
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发表时间：
1998-12-01
期刊：
影响因子：
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通讯作者：
Hirvonen, A
中科院分区：
文献类型：
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作者：
Jourenkova-Mironova, N;Wikman, H;Hirvonen, A
谷胱甘肽S转移酶GSTM1、GSTM3、GSTP1和GSTT1参与了烟草烟雾中多种致癌物质的活性代谢产物的解毒作用。我们用150例肺癌患者和172名正常吸烟者外周血中GSTM1、GSTM1和GSTT1基因的多态性，研究了GSTM3和GSTP1基因的多态性及其与肺癌易感性的关系。病例组GSTM3、AA、AB和BB基因频率分别为70.7%、24.0%和5.3%，对照组分别为72.7%、24.4%和2.9%。病例组AG和GG基因型分别为44.7%、44.0%和11.3%，对照组分别为50.0%、37.2%和12.8%。单独研究时，GSTM3和GSTP1两种基因型均未达到统计学意义，但当GSTM1基因同时缺失时(优势比2.9，95%可信区间0.7-12.1)，GSTM3 AA和GSTP1(AG或GG)联合基因型对肺癌的危险性增加近3倍(优势比2.9，95%可信区间0.7-12.1)。GSTM3 AA和GSTP1(AG或GG)联合基因或GSTM3 AA、GSTP1(AG或GG)和GSTM1零基因联合存在显著的交互作用，这三种先验高危基因的组合使吸烟至少35年的吸烟者患肺癌的风险增加(优势比2.7，95%可信区间1.2-6.0)，但在吸烟量较轻的吸烟者中不存在，这可能是因为具有该基因组合的对照组个体中发现的平均熔炼年限较低。药物遗传学8：495-502。(C)1998年，Lippincott Williams&Wilkins。
Glutathione S-transferases GSTM1, GSTM3, GSTP1 and GSTT1 are involved in the detoxification of active metabolites of several carcinogens in tobacco smoke, We studied the potential role of GSTM3 and GSTP1 gene polymorphisms either separately, or in combination with GSTM1 and GSTT1 gene polymorphisms, in susceptibility to lung cancer using peripheral blood DNA from 150 lung cancer patients and 172 control individuals, all regular smokers, The frequencies of GSTM3, AA, AB and BB genotypes were 70.7%, 24.0% and 5.3% in cases and 72.7%, 24.4% and 2.9% in control individuals respectively, The frequencies of GSTP1, AA, AG and GG genotypes were 44.7%, 44.0% and 11.3% in cases and 50.0%, 37.2% and 12.8% in control individuals respectively, When studied separately neither GSTM3 nor GSTP1 genotypes contributed significantly to the risk of lung cancer, Although failing to reach statistical significance, the combined GSTM3 AA and GSTP1 (AG or GG) genotype conferred a nearly threefold risk when the GSTM1 gene was concurrently lacking (odds ratio 2.9, 95% confidence interval 0.7-12.1), Significant interactions were observed between pack-years of smelting and the combined GSTM3 AA and GSTP1 (AG or GG) genotype, or the combined GSTM3 AA, GSTP1 (AG or GG) and GSTM1 null genotype, The combination of these three a priori at risk genotypes conferred an increased risk of lung cancer among smokers with a history of at least 35 pack-years (odds ratio 2.7, 95% confidence interval 1.2-6.0), but not in lighter smokers, probable because of the lower average number of pack-years of smelting found among control individuals with this genotype combination. Pharmacogenetics 8:495-502. (C) 1998 Lippincott Williams & Wilkins.