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有机氯化合物与 AHR 基因的相互作用与非霍奇金淋巴瘤的风险。

Interaction between organochlorines and the AHR gene, and risk of non-Hodgkin lymphoma.

机构信息

BC Cancer Agency,Vancouver, BC, V5Z 1L3, Canada.

出版信息

Cancer Causes Control. 2010 Jan;21(1):11-22. doi: 10.1007/s10552-009-9429-5. Epub 2009 Sep 26.

Abstract

BACKGROUND

Plasma organochlorines have been implicated to increase the risk of non-Hodgkin lymphoma (NHL), and interaction with the aryl hydrocarbon receptor gene (AHR) may modify this risk.

METHODS

In this case-control study conducted in British Columbia, Canada, five single nucleotide polymorphisms (SNPs) of AHR were genotyped in 422 NHL cases and 459 controls to measure the association between individual SNPs, haplotypes, and risk of NHL. Pre-chemotherapy organochlorine levels were measured and gene-environment interaction analysis was performed.

RESULTS

The IVS1 + 4640G/A SNP was significantly associated with NHL risk, with an odds ratio of 1.32 (95% CI = 1.05-1.65) for G/A or A/A genotypes compared to the G/G genotype. Interactions were observed with PCB 118, a known inducer of AHR, and chlordane-related analytes oxychlordane and trans-nonachlor, although no interactions were statistically significant after controlling for multiple comparisons. The observed interactions were consistent across NHL subtypes.

CONCLUSION

Results suggest that the AHR gene may play a role in determining the risk of NHL with exposure to organochlorines, and highlight the importance of understanding gene-environment interactions.

摘要

背景

血浆有机氯污染物已被认为会增加非霍奇金淋巴瘤(NHL)的风险,而与芳烃受体基因(AHR)的相互作用可能会改变这种风险。

方法

在加拿大不列颠哥伦比亚省进行的这项病例对照研究中,对 422 例 NHL 病例和 459 例对照者的 AHR 中的 5 个单核苷酸多态性(SNP)进行了基因分型,以测量单个 SNP、单倍型与 NHL 风险之间的关联。测定了化疗前的有机氯水平,并进行了基因-环境相互作用分析。

结果

IVS1 + 4640G/A SNP 与 NHL 风险显著相关,与 G/G 基因型相比,G/A 或 A/A 基因型的比值比为 1.32(95%CI=1.05-1.65)。与 PCB 118(一种已知的 AHR 诱导物)和氯丹相关分析物氧氯丹和反式-非氯丹观察到相互作用,但在进行多次比较的控制后,没有相互作用具有统计学意义。观察到的相互作用在 NHL 亚型中是一致的。

结论

结果表明,AHR 基因在确定与有机氯暴露相关的 NHL 风险方面可能起作用,并强调了了解基因-环境相互作用的重要性。

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