CYP1B1与北方地区汉族人群喉癌易感性多基因关联分析

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摘要目的：探讨代谢酶CYP1B1基因CYP1B1*2 142 C/G，CYP1B1*2 355 G/T，CYP1B1*3 4326 C/G多态性与北方地区汉族人群喉癌易感性的关系。方法：采用病例-对照研究的方法，运用多重聚合酶链反应方法（Multi-PCR）及基质辅助激光解析-飞行时间质谱分析技术（MALDI-TOF MS）对200例北方地区汉族人群喉癌患者和200例健康对照组外周血DNA中CYP1B1*2 142 C/G、355 G/T，CYP1B1*3 4326 C/G基因进行多态性研究，并分析上述基因位点之间及基因和烟酒的联合作用与喉癌发生风险的关联强度。结果：携带CYP1B1*2 355 G/T突变型基因型的病例组患病风险高于对照组（OR=2.281，95%CI: 1.142～3.516，P＜0.001），携带CYP1B1*3 4326 C/G突变型基因型的病例组患病风险低于对照组（OR=0.571，95%CI: 0.370～0.882，P=0.011）。C142T355C4326单倍体型具有协同效应，显著增加喉癌风险（Adjusted OR=3.180，95%CI:1.760～5.746，P＜0.001）。在非吸烟及吸烟者中携带CYP1B1*2 355 G/T突变型等位基因的危险度OR分别为2.080（95%CI: 0.742～5.830）、6.322（95%CI: 2.541～15.725，P＜0.001）。结论：CYP1B1基因的多态性与喉癌患病风险密切相关。CYP1B1*2 355 G/T突变型基因是喉癌的风险基因，CYP1B1*3 4326 C/G突变型基因是喉癌的保护基因。CYP1B1*2 142 C/G基因多态性与喉癌易感性无相关性。基因与基因之间具有协同作用，风险基因越多患癌风险越大。烟酒与基因之间无相互协同效应。

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	林发明1
	金建华2
	薛静3
	包其郁4
	刘朝兵5
	倪丽艳1

关键词 ：喉肿瘤, 多态性, 交互作用, SPNs, CYP1B1

Abstract：Objective: To explore the association between functional polymorphisms and combined effect in the CYP1B1 (CYP1B1*2 142 C/G, CYP1B1*2 355 G/T, CYP1B1*3 4326 C/G) enzyme genes and the susceptibility of laryngeal cancer in northern Han Chinese. Methods: A case-control study was performed for 200 northern Han Chinese patients diagnosed with laryngeal cancer and 200 healthy control individuals. The genetic polymorphisms of CYP1B1*2 142 C/G, CYP1B1*2 355 G/T, CYP1B1*3 4326 C/G were examined for the individuals by multi-PCR and Matrix Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF MS) approach. The association of these genetic polymorphisms, smoking, drinking, and the combinations of these factors with the susceptibility of laryngeal cancer was statistically evaluated. Results: The frequencies of CYP1B1*2 355 G/T, CYP1B1*3 4326 C/G gene polymorphisms in the patient cohort were significantly different with those in the control cohort (P<0.001, P=0.007 respectively). Compared to the control cohort, a higher risk laryngeal cancer was observed for the carriers of variant genotypes of CYP1B1*2 355T(adjusted OR=2.281,95%CI: 1.142-3.516, P<0.001) and the mutation allele CYP1B1*3 4326G carriers had lower laryngeal cancer risk (adjusted OR=0.571, 95%CI: 0.370-0.882, P=0.011). Polymorphisms at these three loci presented a joint effect. The haplotype C142T355C4326 was associated with a significantly higher laryngeal cancer risk (adjusted OR=3.180, 95% CI:1.760-5.746, P<0.001) compared to the haplotype C142G355C4326. The adjusted ORs for the individuals with GT/TT genotype at CYP1B1*2 355 G/T were 2.080 (95% CI: 0.742-5.830, P<0.001) and 6.322 (95% CI: 2.541-15.725, P<0.001) respectively for the non-smokers and smokers. Conclusion: Genetic polymorphism of CYP1B1 is associated with risk of laryngeal cancer. CYP1B1*2 355T increase the laryngeal cancer risk and CYP1B1*3 4326G reduces the risk. The association between CYP1B1*2 142C/G polymorphism with the risk of laryngeal cancer dose not found. These polymorphisms showed a joint effect on the susceptibility to laryngeal cancer, presenting as higher risk with more risky factors included. Environmental factors, smoking and drinking, showed a non-collaborative effect with two risky genetic factors.

Key words： laryngeal neoplasm polymorphism interaction SPNs CYP1B1

收稿日期: 2013-11-09

基金资助:温州市科技局科研基金资助项目（H20090025）；浙江省中医药科技局科研基金资助项目（2012ZB106）。

通讯作者: 倪丽艳，主任医师，Email：nily2001@126.com。

作者简介: 林发明（1986-），男，浙江湖州人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2014/V44/I3/177

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