CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma
CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma
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DOI：
10.1016/j.mrfmmm.2005.01.027
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发表时间：
2005-07-01
影响因子：
2.3
通讯作者：
Szyfter, K
中科院分区：
文献类型：
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作者：
Gajecka, M;Rydzanicz, M;Szyfter, K
控制致癌物代谢的基因多态性本文对289例喉鳞状细胞癌患者和316例正常对照进行了细胞色素P450（CYP 1A 1）、细胞色素P450（CYP 2D 6）、细胞色素P450（CYP 2 E1）、NAT 2、谷胱甘肽S转移酶（GSTM 1）、谷胱甘肽S转移酶（GSTT 1）的病例对照研究。都是来自波兰同一地区的白种男性，目前吸烟。采用PCR-RFLP和多重PCR对DNA样本进行基因分型。比较两组的变异频率; CYP 1A 1 *1/*4、CYP 2D 6 *4/*4、NAT 2 *4/*6A基因型以及CYP 1A 1 *4、CYP 2D 6 *4、NAT 2 *4等位基因，在病例组中的发生率明显高于对照组，表明它们在喉鳞状细胞癌中起着“风险升高”因素的作用。组合基因型，其特征是在一个以上的基因座存在的“风险升高”的变体，经常发生在一起的GSTM 1基因的无效变体和纯合子XPD A/A（Lys 751 Gln，A35931 C）基因型。此外，我们鉴定了一些“保护性”变异，在对照组中比病例中更常见，即NAT 2 *6A/*6A和NAT 2 * 5 B/*6A基因型。“风险”或“保护”基因型/等位基因的分布似乎与年龄有关，因为风险基因在“年轻”病例组中更常见（
Polymorphisms in the selected genes controlling carcinogen metabolism (CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1, GSTT1) considered separately or in different combinations, were investigated for an association with tobacco smoke-associated squamous cell carcinoma (SCC) of the larynx.The case-control study was performed in 289 patients with laryngeal SCC and in 316 cancer-free controls; all were Caucasian males from the same region of Poland and current tobacco smokers. The DNA samples were genotyped using PCR-RFLP and multiplex PCR. The variants' frequencies in both groups were compared; odds ratios and their 95% confidence intervals were calculated by logistic regression analyses.The CYP1A1*1/*4, CYP2D6*4/*4, NAT2*4/*6A genotypes, as well as the CYP1A1*4, CYP2D6*4 and NAT2*4 alleles, were found at significantly higher frequencies in cases than in controls indicating their role as "risk-elevating" factors in laryngeal SCC. Combined genotypes, characterized by the presence of the "risk-elevating" variants at more than one locus, often occurred together with the null variant of the GSTM1 gene and homozygous XPD A/A (Lys751Gln, A35931C) genotype. Furthermore, we identified some "protective" variants, found more frequently in controls than in cases, i.e. the NAT2*6A/*6A and NAT2*5B/*6A genotypes. A distribution of "risk" or "protection" genotypes/alleles seems to be connected with age as an occurrence or risk genes was more frequent in the group of "young" cases (