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外源性代谢途径基因的遗传变异、个人染发剂使用情况与非霍奇金淋巴瘤风险

Genetic variations in xenobiotic metabolic pathway genes, personal hair dye use, and risk of non-Hodgkin lymphoma.

作者信息

Zhang Yawei, Hughes Kathryn J, Zahm Shelia Hoar, Zhang Yaqun, Holford Theodore R, Dai Li, Bai Yana, Han Xuesong, Qin Qin, Lan Qing, Rothman Nathaniel, Zhu Yong, Leaderer Brian, Zheng Tongzhang

机构信息

School of Public Health, Yale University, New Haven, Connecticut 06520-8034, USA.

出版信息

Am J Epidemiol. 2009 Nov 15;170(10):1222-30. doi: 10.1093/aje/kwp263. Epub 2009 Oct 12.

Abstract

From 1996 to 2000, the authors conducted a population-based case-control study among Connecticut women to test the hypothesis that genetic variation in xenobiotic metabolic pathway genes modifies the relation between hair dye use and risk of non-Hodgkin lymphoma. No effect modifications were found for women who started using hair dyes in 1980 or afterward. For women who started using hair dye before 1980 as compared with never users, a statistically significantly increased risk of non-Hodgkin lymphoma was found for carriers of CYP2C9 Ex3-52C>T TT/CT genotypes (odds ratio (OR) = 2.9, 95% confidence interval (CI): 1.4, 6.1), CYP2E1 -332T>A AT/AA genotypes (OR = 2.0, 95% CI: 1.2, 3.4), a homozygous or heterozygous 3-base-pair deletion in intron 6 of GSTM3 (OR = 2.3, 95% CI: 1.3, 4.1), GSTP1 Ex5-24A>G AA genotypes (OR = 1.8, 95% CI: 1.1, 2.9), or NAT2 genotypes conferring intermediate/rapid acetylator status (OR = 1.6, 95% CI: 1.0, 2.7). The observed associations were mainly seen for follicular lymphoma. In contrast, no significantly increased risk was observed for starting hair dye use before 1980 (relative to never use) among women who were homozygous wild-type for the CYP2C9, CYP2E1, or GSTM3 polymorphisms, women carrying 1 or 2 copies of the variant GSTP1 allele, or women who were slow NAT2 acetylators. A possible role of genetic variation in xenobiotic metabolism in the carcinogenicity of hair dye use needs to be confirmed in larger studies.

摘要

1996年至2000年期间,作者在康涅狄格州女性中开展了一项基于人群的病例对照研究,以检验如下假设:外源性物质代谢途径基因的遗传变异会改变染发剂使用与非霍奇金淋巴瘤风险之间的关系。对于1980年或之后开始使用染发剂的女性,未发现效应修饰。与从未使用过染发剂的女性相比,对于CYP2C9 Ex3-52C>T TT/CT基因型携带者(比值比(OR)=2.9,95%置信区间(CI):1.4,6.1)、CYP2E1 -332T>A AT/AA基因型携带者(OR =2.0,95% CI:1.2,3.4)、GSTM3第6内含子纯合或杂合3碱基对缺失者(OR =2.3,95% CI:1.3,4.1)、GSTP1 Ex5-24A>G AA基因型携带者(OR =1.8,95% CI:1.1,2.9)或具有中等/快速乙酰化状态的NAT2基因型携带者,1980年之前开始使用染发剂的女性患非霍奇金淋巴瘤的风险在统计学上显著增加。观察到的关联主要见于滤泡性淋巴瘤。相比之下,对于CYP2C9、CYP2E1或GSTM3多态性为纯合野生型的女性、携带1个或2个GSTP1变异等位基因拷贝的女性或NAT2慢乙酰化者,未观察到1980年之前开始使用染发剂(相对于从未使用)会使风险显著增加。外源性物质代谢中的遗传变异在染发剂使用致癌性方面的可能作用需要在更大规模的研究中得到证实。

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