Yadav Sunishtha S, Seth Shilpi, Khan Anwar J, Maurya Shailendra S, Dhawan Ankur, Pant Sidharth, Pant Mohan C, Parmar Devendra
Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, M.G. Marg, Lucknow 226 001, UP, India.
Department of Radiotherapy, King George's Medical University, Lucknow 226 001, India.
Appl Transl Genom. 2013 Aug 27;3(1):8-13. doi: 10.1016/j.atg.2013.07.002. eCollection 2014 Mar 1.
The present case-control study involving 750 cases and equal number of healthy controls investigates the association of polymorphism in cytochrome P450 2C9 (CYP2C9) with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving chemotherapy or combination of radio-chemotherapy. The frequency of heterozygous or homozygous genotypes of CYP2C92 & CYP2C93, which leads to the poor metabolizer (PM) genotype was significantly higher in HNSCC cases when compared to the healthy controls resulting in significantly increased risk in the cases. Tobacco use in the form of tobacco smoking or tobacco chewing was found to increase the risk several fold in cases when compared to the non-tobacco users. Likewise, alcohol intake in cases with variant genotypes of CYP2C92 or CYP2C93 also significantly increased the HNSCC risk in cases when compared to non-alcohol users. Further, majority of the cases carrying variant alleles of both CYP2C92 or CYP2C93 were found to respond poorly to the chemotherapy or combination of radio-chemotherapy. The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome.
本病例对照研究纳入了750例病例及同等数量的健康对照，旨在探究细胞色素P450 2C9（CYP2C9）基因多态性与头颈部鳞状细胞癌（HNSCC）的关联，以及接受化疗或放化疗联合治疗患者的反应。与健康对照相比，导致代谢不良（PM）基因型的CYP2C92和CYP2C93杂合或纯合基因型在HNSCC病例中的频率显著更高，从而使病例的风险显著增加。与不使用烟草者相比，以吸烟或嚼烟形式使用烟草会使病例的风险增加数倍。同样，与不饮酒者相比，携带CYP2C92或CYP2C93变异基因型的病例饮酒也会显著增加HNSCC风险。此外，发现大多数携带CYP2C92或CYP2C93变异等位基因的病例对化疗或放化疗联合治疗反应较差。数据表明CYP2C9基因多态性与HNSCC及治疗结果之间存在显著关联。
