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N-乙酰基转移酶 1 和 2 基因序列变异与头颈部癌症风险。

N-acetyltransferase 1 and 2 gene sequence variants and risk of head and neck cancer.

机构信息

Department of Basic Oncology, I.U. Oncology Institute, 34093, Capa, Istanbul, Turkey.

出版信息

Mol Biol Rep. 2010 Oct;37(7):3217-26. doi: 10.1007/s11033-009-9905-8. Epub 2009 Nov 8.

DOI:10.1007/s11033-009-9905-8
PMID:19898993
Abstract

Polymorphisms that alter the function of genes involved in the activation or detoxification of carcinogenic compounds can influence an individuals risk of developing cancer. Polymorphic changes modulating the acetylation capacity of the N-acetyltransferase (NAT) genes have been implicated in the risk of developing cancer. In this study the role of genetically determined individual NAT1 and NAT2 genotypes, haplotypes and haplotype combinations in the predisposition to head and neck cancer was investigated. Polymorphic regions of the NAT1 and NAT2 genes were analyzed in patients with head and neck cancer and healthy individuals by polymerase chain reaction-restriction fragment length polymorphism. Distribution of the genotypes, allele frequencies, diplotypes and haplotypes and correlation with clinical characteristics were evaluated. No association was observed between the NAT13, NAT110, NAT111, NAT25 and NAT26 genotypes and risk of head and neck cancer. The NAT27 slow genotype was associated with reduced risk of disease. A significant association was observed between the fast acetylator NAT24/NAT110 diplotype and risk of head and neck cancer. Combined haplotypes harboring the T1088A and C1095A variants characterizing the NAT1*10 allele were associated with increased risk. Our results suggest that NAT1 and NAT2 gene combinations may influence the risk of developing head and neck cancer.

摘要

基因的多态性改变了参与致癌化合物激活或解毒的基因的功能,可能会影响个体患癌症的风险。调节 N-乙酰基转移酶(NAT)基因乙酰化能力的多态性变化与癌症风险有关。在这项研究中,研究了个体 NAT1 和 NAT2 基因的遗传决定型基因型、单倍型和单倍型组合在头颈部癌症易感性中的作用。通过聚合酶链反应-限制性片段长度多态性对头颈部癌症患者和健康个体的 NAT1 和 NAT2 基因的多态性区域进行了分析。评估了基因型、等位基因频率、二倍型和单倍型的分布以及与临床特征的相关性。NAT13、NAT110、NAT111、NAT25 和 NAT26 基因型与头颈部癌症风险之间没有关联。NAT27 慢基因型与疾病风险降低相关。快速乙酰化 NAT24/NAT110 二倍型与头颈部癌症风险之间存在显著关联。携带 NATI*10 等位基因特征的 T1088A 和 C1095A 变体的组合单倍型与风险增加相关。我们的结果表明,NAT1 和 NAT2 基因组合可能影响头颈部癌症的发病风险。

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