Shah Parag P, Singh Arvind P, Singh Madhu, Mathur Neeraj, Pant Mohan C, Mishra Bhartendu N, Parmar Devendra
Developmental Toxicology Division, Industrial Toxicology Research Centre, Lucknow 226001, India.
Mutat Res. 2008 Mar 1;639(1-2):1-10. doi: 10.1016/j.mrfmmm.2007.10.006. Epub 2007 Oct 30.
Lung cancer is the most common cause of death throughout the world with cigarette smoking being established as the major etiological factor in lung cancer. Since not much information is available regarding the polymorphism in drug metabolizing enzymes and lung cancer risk in the Indian population, the present case-control study attempted to investigate the association of polymorphisms in cytochrome P450 1A1 (CYP1A1) and glutathione-S-transferase M1 (GSTM1) with risk to squamous cell carcinoma of lung malignancy. Patients suffering from lung cancer (n=200) and visiting OPD facility of Department of Radiotherapy, King George's Medical University, Lucknow, were included in the study. Equal number (n=200) of age and sex matched healthy individuals were also enrolled in the study. Our data revealed that the variant genotypes of CYP1A12A, CYP1A12C and CYP1A14 were found to be over represented in the lung cancer patients when compared to controls. CYP1A12A variant genotypes (combined heterozygous and mutant genotypes) revealed significant association towards the lung cancer risk (OR: 1.93, 95%CI: 1.28-2.89, p=0.002). Likewise, GSTM1 null genotypes were found to be over represented in patients when compared to controls. Haplotype analysis revealed that CYP1A1 haplotype, C-G-C increased the lung cancer risk (OR: 3.90, 95%CI: 1.00-15.04, p=0.025) in the patients. The lung cancer risk was increased several two-to fourfold in the patients carrying the genotype combinations of CYP1A1*2A and GSTM1 suggesting the role of gene-gene interaction in lung cancer. Cigarette smoking or tobacco chewing or alcohol consumption was also found to interact with CYP1A1 genotypes in increasing the risk to lung cancer further demonstrating the role of gene-environment interaction in development of lung cancer.
肺癌是全球最常见的死因，吸烟被确认为肺癌的主要病因。由于关于印度人群中药物代谢酶多态性与肺癌风险的信息不多，本病例对照研究试图调查细胞色素P450 1A1（CYP1A1）和谷胱甘肽 - S - 转移酶M1（GSTM1）的多态性与肺恶性鳞状细胞癌风险的关联。纳入研究的患者为患有肺癌（n = 200）且前往勒克瑙乔治国王医科大学放射治疗科门诊的患者。研究还纳入了数量相等（n = 200）的年龄和性别匹配的健康个体。我们的数据显示，与对照组相比，CYP1A12A、CYP1A12C和CYP1A14的变异基因型在肺癌患者中出现的比例过高。CYP1A12A变异基因型（杂合子和突变基因型组合）与肺癌风险存在显著关联（比值比：1.93，95%置信区间：1.28 - 2.89，p = 0.002）。同样，与对照组相比，GSTM1无效基因型在患者中出现的比例过高。单倍型分析显示，CYP1A1单倍型C - G - C增加了患者的肺癌风险（比值比：3.90，95%置信区间：1.00 - 至15.04，p = 0.025）。携带CYP1A1*2A和GSTM1基因型组合的患者肺癌风险增加了两到四倍，表明基因 - 基因相互作用在肺癌中的作用。还发现吸烟、嚼烟草或饮酒也与CYP1A1基因型相互作用，进一步增加肺癌风险，这进一步证明了基因 - 环境相互作用在肺癌发生中的作用。
