Association between Cancer Risk and Drug-metabolizing Enzyme Gene (CYP2A6, CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1) Polymorphisms in Cases of Lung Cancer in Japan
Association between Cancer Risk and Drug-metabolizing Enzyme Gene (CYP2A6, CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1) Polymorphisms in Cases of Lung Cancer in Japan
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DOI：
10.2133/dmpk.dmpk-11-rg-046
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发表时间：
2011-01-01
影响因子：
2.1
通讯作者：
Hiratsuka, Masahiro
中科院分区：
文献类型：
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作者：
Tamaki, Yuichiro;Arai, Tomio;Hiratsuka, Masahiro
参与致癌物代谢的酶的遗传多态性被认为可以改变个体对肺癌的易感性。本研究的目的是调查日本肺癌病例与细胞色素P450（CYP）2A 6（CYP 2A 6 *4）、CYP 2A 13（CYP 2A 13 *1-*10）、CYP 4 B1（CYP 4 B1 *1-*7）、磺基转移酶1A 1（SULT 1A 1 *2）、谷胱甘肽S-转移酶M1（GSTM 1 null）和谷胱甘肽S-转移酶T1（GSTT 1 null）的变异等位基因之间的关系。我们调查了这些多态性在192例肺癌患者和203例年龄和性别匹配的无癌对照中的分布。采用多种技术，包括等位基因特异性PCR，杂交探针测定，多重PCR，变性高效液相色谱（DHPLC），和直接测序的多态性进行了分析。我们还调查了等位基因和基因型频率及其与肺癌风险、人口统计学因素和吸烟状况的关系。CYP 2A 6 *4/*4基因型在肺癌组中的检出率为3.6%，在对照组中的检出率为9.4%（校正OR = 0.36，95% CI = 0.15-0.88，P = 0.025）。相反，已知的CYP 2A 13、CYP 4 B1、SULT 1A 1、GSTM 1和GSTT 1多态性与肺癌之间没有关联。这些数据表明，CYP 2A 6缺失可能与研究的日本人群中的肺癌相关。
Genetic polymorphisms of enzymes involved in the metabolism of carcinogens are suggested to modify an individual's susceptibility to lung cancer. The purpose of this study was to investigate the relationship between lung cancer cases in Japan and variant alleles of cytochrome P450 (CYP) 2A6 (CYP2A6*4), CYP2A13 (CYP2A13*1-*10), CYP4B1 (CYP4B1*1-*7), sulfotransferase 1A1 (SULT1A1*2), glutathione S-transferase M1 (GSTM1 null), and glutathione S-transferase T1 (GSTT1 null). We investigated the distribution of these polymorphisms in 192 lung cancer patients and in 203 age- and sex-matched cancer-free controls. The polymorphisms were analyzed using various techniques including allele-specific PCR, hybridization probe assay, multiplex PCR, denaturing high-performance liquid chromatography (DHPLC), and direct sequencing. We also investigated allele and genotype frequencies and their association with lung cancer risk, demographic factors, and smoking status. The prevalence of the CYP2A6*4/*4 genotype in lung cancer cases was 3.6%, compared with 9.4% in the controls (adjusted OR = 0.36, 95% CI = 0.15-0.88, P = 0.025). In contrast, there was no association between the known CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1 polymorphisms and lung cancer. These data indicate that CYP2A6 deletions may be associated with lung cancer in the Japanese population studied.