Singh Arvind P, Shah Parag P, Mathur Neeraj, Buters Jeroen T M, Pant Mohan C, Parmar Devendra
Developmental Toxicology Division, Industrial Toxicology Research Centre, Lucknow 226001, India.
Mutat Res. 2008 Mar 1;639(1-2):11-9. doi: 10.1016/j.mrfmmm.2007.10.007. Epub 2007 Nov 5.
Cytochrome P4501B1 (CYP1B1), a polycyclic aromatic hydrocarbon (PAH) metabolizing CYP, is genetically polymorphic in humans and may be involved in the individual susceptibility to chemical-induced cancer. In the present study, genotype and haplotype frequencies of four single nucleotide polymorphisms (SNPs) in CYP1B1 that cause amino acid changes (Arg-Gly at codon 48, Ala-Ser at codon 119, Leu-Val at codon 432 and Asn-Ser at codon 453) were studied in 150 cases suffering from head and neck squamous cell carcinoma (HNSCC) and in an equal number of controls. A significant difference was observed for the distribution of variant genotypes of Arg48Gly (CYP1B12) and Ala119Ser (CYP1B12) polymorphisms of CYP1B1 in cases versus controls. No significant differences were observed for the distribution of variant genotypes-Leu432Val (CYP1B13) and Asn453Ser (CYP1B14), respectively. When the four SNPs were analyzed using a haplotype approach, SNPs at codon 48 (Arg48Gly) and codon 119 (Ala119Ser) exhibited complete linkage disequilibrium (LD) in all the cases and controls. Significant differences in the distribution of the two haplotypes (G-T-C-A and G-T-G-A) were observed both in the cases and in controls. Furthermore, our data indicates a several fold increase in risk in the cases who use tobacco (cigarette smoking or tobacco chewing) or alcohol with the variant genotypes of CYP1B1 (CYP1B12 and CYP1B13) suggesting the role of gene-environment interaction in the susceptibility to HNSCC.
细胞色素P4501B1（CYP1B1）是一种参与多环芳烃（PAH）代谢的细胞色素P450，在人类中具有基因多态性，可能与个体对化学物质诱导癌症的易感性有关。在本研究中，我们对150例头颈部鳞状细胞癌（HNSCC）患者和同等数量的对照者，研究了CYP1B1中四个导致氨基酸改变的单核苷酸多态性（SNP）（密码子48处的Arg-Gly、密码子119处的Ala-Ser、密码子432处的Leu-Val和密码子453处的Asn-Ser）的基因型和单倍型频率。在病例组和对照组中，观察到CYP1B1的Arg48Gly（CYP1B12）和Ala119Ser（CYP1B12）多态性的变异基因型分布存在显著差异。而密码子432处的Leu432Val（CYP1B13）和密码子453处的Asn453Ser（CYP1B14）变异基因型的分布，在病例组和对照组中均未观察到显著差异。当使用单倍型方法分析这四个SNP时，密码子48（Arg48Gly）和密码子119（Ala119Ser）处的SNP在所有病例和对照中均表现出完全连锁不平衡（LD）。在病例组和对照组中，均观察到两种单倍型（G-T-C-A和G-T-G-A）的分布存在显著差异。此外，我们的数据表明，携带CYP1B1变异基因型（CYP1B12和CYP1B13）的烟草使用者（吸烟或咀嚼烟草）或饮酒者患HNSCC的风险增加了几倍，这表明基因-环境相互作用在HNSCC易感性中发挥了作用。
