CYP1A1 MspI 和 GST 多态性与基因-环境相互作用及在印度人群中上呼吸道消化道癌症的风险
Gene-environment interactions associated with CYP1A1 MspI and GST polymorphisms and the risk of upper aerodigestive tract cancers in an Indian population.
机构信息
Pharmacogenomics Laboratory, Department of Pharmacology, Jawaharlal Institute of Post-Graduate Medical Education and Research, Pondicherry 605006, India.
出版信息
J Cancer Res Clin Oncol. 2010 Jun;136(6):945-51. doi: 10.1007/s00432-009-0738-6. Epub 2009 Dec 10.
PURPOSE
Genetic risk to tobacco related cancers are associated with polymorphisms in CYP1A1 and GST, which are involved in the metabolic activation and detoxification of carcinogens. The genetic variations in these drug-metabolizing enzymes may alter the susceptibility to UADT cancers triggered by environmental exposures. The hospital-based case-control study evaluated the impact of combined CYP1A1 MspI and GST (M1 & T1) polymorphisms among the individuals exposed to environmental risk factors as modulators in the risk of UADT cancers in Tamilians, a population of south India.
METHODS
The unrelated histopathologically confirmed 408 cases and 220 population-based controls matched by age and gender were genotyped for CYP1A1 MspI, GSTM1 and GSTT1 polymorphisms using PCR based methods. To investigate the potential gene-environment interactions, analyses were carried out stratifying by smoking and tobacco chewing status using SPSS software.
RESULTS
The combination of genes and environment interactions by stratified analyses revealed significant interactions among the habitual tobacco smokers (CYP1A1 MspI & GSTM1 null: OR 14.06; 95% CI 3.90-50.68, CYP1A1 MspI & GSTT1 null: OR 33.28; 95% CI 4.24-261.19) and tobacco chewers (CYP1A1 MspI & GSTM1 null: OR 20.51; 95% CI 6.77-62.13, CYP1A1 MspI & GSTT1 null: OR 79.35; 95% CI 10.40-605.55) on the multiplicative scale.
CONCLUSION
Our findings have indicated that the individuals polymorphic for CYP1A1 MspI either with GSTM1 null or with GSTT1 null genotypes revealed an increased risk for UADT cancers than that ascribed to a single susceptible gene among the tobacco users in the population [single gene risk among smokers and chewers, respectively, for CYP1A1 MspI (OR 6.43; 95% CI 3.69-11.21); (OR 10.24; 95% CI 5.95-17.60), GSTM10 (OR 3.77; 95% CI 1.94-7.37); (OR 7.97 95% CI 4.10-15.76) and GSTT10 (OR 6.95 95% CI 2.88-16.77); (OR 25.83 95% CI 7.78-85.76).
目的
与烟草相关癌症的遗传风险与 CYP1A1 和 GST 的多态性有关，这些基因参与致癌物质的代谢激活和解毒。这些药物代谢酶的遗传变异可能改变环境暴露引发的 UADT 癌症的易感性。这项基于医院的病例对照研究评估了 CYP1A1 MspI 和 GST（M1 和 T1）多态性在接触环境危险因素的个体中的联合作用，作为印度南部泰米尔人 UADT 癌症风险的调节剂。
方法
采用基于 PCR 的方法，对 408 例经组织病理学证实的无关病例和 220 例年龄和性别匹配的人群对照进行 CYP1A1 MspI、GSTM1 和 GSTT1 多态性的基因分型。为了研究潜在的基因-环境相互作用，使用 SPSS 软件对吸烟和咀嚼烟草状态进行分层分析。
结果
分层分析的基因与环境相互作用的组合显示，习惯性烟草吸烟者（CYP1A1 MspI 和 GSTM1 缺失：OR 14.06；95%CI 3.90-50.68，CYP1A1 MspI 和 GSTT1 缺失：OR 33.28；95%CI 4.24-261.19）和咀嚼烟草者（CYP1A1 MspI 和 GSTM1 缺失：OR 20.51；95%CI 6.77-62.13，CYP1A1 MspI 和 GSTT1 缺失：OR 79.35；95%CI 10.40-605.55）之间存在显著的相互作用。
结论
我们的研究结果表明，CYP1A1 MspI 多态性的个体，无论是 GSTM1 缺失还是 GSTT1 缺失基因型，与烟草使用者中单一易感基因相比，UADT 癌症的风险增加（吸烟者和咀嚼者的单基因风险分别为 CYP1A1 MspI（OR 6.43；95%CI 3.69-11.21）；（OR 10.24；95%CI 5.95-17.60），GSTM10（OR 3.77；95%CI 1.94-7.37）；（OR 7.97 95%CI 4.10-15.76）和 GSTT10（OR 6.95 95%CI 2.88-16.77）；（OR 25.83 95%CI 7.78-85.76）。
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