Hietanen E, Husgafvel-Pursiainen K, Vainio H
Department of Clinical Physiology, University of Turku, Finland.
Environ Health Perspect. 1997 Jun;105 Suppl 4(Suppl 4):749-54. doi: 10.1289/ehp.97105s4749.
Increased risk of environmentally induced cancer is associated with various types of exposures and host factors, including differences in carcinogen metabolism. Since many carcinogenic compounds require metabolic activation to enable them to react with cellular macromolecules, individual features of carcinogen metabolism may play an essential role in the development of environmental cancer. In this context, cigarette smoking has often been the main type of carcinogenic exposure examined in human studies. Increasing attention has recently been paid to the dose level at which individual susceptibility may be observed. Present studies on increased risk of smoking-related lung cancer associated with phenotypic or genotypic variation of the genes encoding for CYP1A1 or CYP2D6 enzymes are summarized. Similarly, higher risks of lung or bladder cancer seen at various levels of smoking in association with polymorphism of the glutathione S-transferase gene GSTM1 or NAT1 and NAT2 genes involved in N-acetylation are reviewed. Finally, the influence of CYP2E1, GSTM1, or the combined at-risk genotype on the risk of hepatocellular carcinoma in smokers is briefly discussed.
环境诱发癌症风险的增加与多种类型的暴露及宿主因素有关，包括致癌物代谢的差异。由于许多致癌化合物需要代谢激活才能与细胞大分子发生反应，致癌物代谢的个体特征可能在环境癌症的发生发展中起关键作用。在此背景下，吸烟常常是人体研究中所考察的主要致癌暴露类型。最近，人们越来越关注能够观察到个体易感性的剂量水平。本文总结了目前关于与编码CYP1A1或CYP2D6酶的基因的表型或基因型变异相关的吸烟相关肺癌风险增加的研究。同样，本文还综述了在不同吸烟水平下，与参与N - 乙酰化的谷胱甘肽S - 转移酶基因GSTM1或NAT1和NAT2基因的多态性相关的肺癌或膀胱癌的较高风险。最后，简要讨论了CYP2E1、GSTM1或合并的高危基因型对吸烟者肝细胞癌风险的影响。
