CYP2C9 基因型并不影响一般人群中与烟草相关的癌症风险。

CYP2C9 genotype does not affect risk of tobacco-related cancer in the general population.

机构信息

Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.

出版信息

Cancer Epidemiol. 2010 Apr;34(2):178-83. doi: 10.1016/j.canep.2010.01.003. Epub 2010 Feb 8.

DOI:10.1016/j.canep.2010.01.003

PMID:20117066

Abstract

BACKGROUND

CYP2C9 enzymes are important in the metabolism of procarcinogenic chemicals such as polycyclic aromatic hydrocarbons (PAHs) found in tobacco smoke. Two functional variants in the CYP2C9 gene (CYP2C92 and CYP2C93) are known to be associated with decreased enzyme activity towards tolbutamide and warfarin, while this has not been investigated for PAHs. We hypothesised that these two variants in the CYP2C9 gene influence risk of tobacco-related cancer.

METHODS

In a prospective study of the general population (n=10 392) with 60 years of follow-up, the Copenhagen City Heart Study, we associated two variants of CYP2C9 (CYP2C92 and CYP2C93) with risk of tobacco-related cancer and all cancer. All results were re-tested in a cross-sectional study of the general population (n=36 856), the Copenhagen General Population Study.

RESULTS

We found no association between any of the CYP2C9 genotypes and risk of tobacco-related cancer, individual tobacco-related cancers, or all cancer. For the combined carriers (any CYP2C92 or CYP2C93 heterozygotes or homozygotes) vs. non-carriers we had 90% statistical power to exclude measures of relative risks below/above 0.8/1.2 and 0.9/1.1 in the Copenhagen City Heart Study and below/above 0.8/1.3 and 0.9/1.1 in the Copenhagen General Population Study for tobacco-related cancer and all cancer, respectively.

CONCLUSION

Genetic variations in CYP2C9 do not affect risk of tobacco-related cancers.

摘要

背景

CYP2C9 酶在代谢前致癌物如烟草烟雾中的多环芳烃（PAHs）中起着重要作用。CYP2C9 基因中的两个功能变体（CYP2C92 和 CYP2C93）已知与甲苯磺丁脲和华法林的酶活性降低有关，而这一点尚未在 PAHs 中进行研究。我们假设 CYP2C9 基因中的这两个变体影响与烟草相关的癌症风险。

方法

在一项针对普通人群（n=10392）的前瞻性研究中，对哥本哈根城市心脏研究进行了 60 年的随访，我们将 CYP2C9 的两个变体（CYP2C92 和 CYP2C93）与与烟草相关的癌症和所有癌症的风险相关联。所有结果均在普通人群的横断面研究（n=36856），哥本哈根普通人群研究中进行了重新测试。

结果

我们没有发现任何 CYP2C9 基因型与与烟草相关的癌症、个体与烟草相关的癌症或所有癌症的风险之间存在关联。对于联合携带者（任何 CYP2C92 或 CYP2C93 杂合子或纯合子）与非携带者相比，我们在哥本哈根城市心脏研究中具有 90%的统计效力，可以排除相对风险低于/高于 0.8/1.2 和 0.9/1.1 的测量值，以及在哥本哈根普通人群研究中低于/高于 0.8/1.3 和 0.9/1.1 的测量值，分别用于与烟草相关的癌症和所有癌症。