Department of Otolaryngology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Oral Dis. 2010 Nov;16(8):760-8. doi: 10.1111/j.1601-0825.2010.01683.x.
To examine role of genetic variants of CYP2A13 and UGT1A7 genes, involved in activation and detoxification of tobacco carcinogens, with risk of head and neck cancer as well as to assess the potential modifying role of gene-gene and gene-environment interactions.
203 head and neck cancer patients and 201 healthy controls were genotyped for functional polymorphisms of CYP2A13 and UGT1A7 genes using polymerase chain reaction-restriction fragment length polymorphism, denaturing high-performance liquid chromatography and sequencing.
We identified two novel polymorphisms T478C and T494C in CYP2A13 gene which were associated with significantly reduced risk of cancer (OR 0.37; 95% CI 0.19-0.71; P < 0.05). A CYP2A13 haplotype carrying variant alleles of T478C/T494C was found to be associated with reduced risk of head and neck cancer (OR 0.42; 95% CI 0.22-0.78; P = 0. 005). Mutant 'T' allele of CYP2A13 C578T polymorphism was found to be present in cancer patients only. A sevenfold increased risk of cancer was observed in smokers with UGT1A7 low activity genotypes (OR 7.01; 95% CI 1.02-48.37; P < 0.05). UGT1A7 haplotype carrying C allele (T622C) showed 10-fold increased risk of cancer (OR 10.12; 95% CI 1.29-79.4; P < 0.05).
Interplay between genetic variants of CYP2A13 and UGT1A7 genes and smoking may modulate susceptibility to head and neck cancer.
研究细胞色素 P450 2A13（CYP2A13）和尿苷二磷酸葡萄糖醛酸转移酶 1A7（UGT1A7）基因的遗传变异在烟草致癌物质的激活和解毒中的作用，及其与头颈部癌症风险的关系，并评估基因-基因和基因-环境相互作用的潜在修饰作用。
采用聚合酶链反应-限制性片段长度多态性、变性高效液相色谱和测序方法，对 203 例头颈部癌症患者和 201 例健康对照者 CYP2A13 和 UGT1A7 基因的功能多态性进行基因分型。
我们在 CYP2A13 基因中发现了两个新的多态性 T478C 和 T494C，它们与癌症风险显著降低相关（OR 0.37；95%CI 0.19-0.71；P < 0.05）。携带 T478C/T494C 变异等位基因的 CYP2A13 单倍型与头颈部癌症风险降低相关（OR 0.42；95%CI 0.22-0.78；P = 0.005）。CYP2A13 C578T 多态性的突变‘T’等位基因仅存在于癌症患者中。UGT1A7 低活性基因型的吸烟者患癌症的风险增加了 7 倍（OR 7.01；95%CI 1.02-48.37；P < 0.05）。携带 C 等位基因（T622C）的 UGT1A7 单倍型患癌症的风险增加了 10 倍（OR 10.12；95%CI 1.29-79.4；P < 0.05）。
CYP2A13 和 UGT1A7 基因的遗传变异与吸烟之间的相互作用可能调节头颈部癌症的易感性。
