Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-Ku, 812-8582, Fukuoka, Japan,
Environ Health Prev Med. 2002 May;7(2):47-59. doi: 10.1007/BF02897330.
Chronic inhalation of cigarette smoke is a major risk factor for the development of lung cancer. It has been suggested that genetic susceptibility may contribute to the risk, because only a small portion of smokers develops the disease. Several polymorphisms that involve the metabolic activation or detoxification of carcinogens derived from cigarette smoke have been found to be associated with lung cancer risk. Many studies have focused on the relation between the distribution of polymorphic variants of different forms of the metabolic enzymes and lung cancer susceptibility. In this respect two groups of genetic polymorphisms of enzymes involved in xenobiotic metabolism, cytochrome P450 (CYP) and glutathione S-transferases (GSTs), have been discussed.CYP multigene superfamily consists of 10 subfamilies (CYP1-CYP10). A positive association between development of lung cancer and the mutant homozygous genotype ofCYP1A1 gene has been reported in several Japanese populations but such an association has not been observed in either Caucasians or African-Americans. The relation betweenCYP2D6 and lung cancer remains conflicting and inconclusive. Several polymorphisms have been identified at theCYP2E1 locus. No definitive link between the polymorphisms ofCYP2E1 and the risk of lung cancer has, however, been identified. The role of otherCYP2 isoforms in lung carcinogenesis has not been sufficiently investigated.GSTs form a superfamily of genes consisting of five distinct families, namedGSTA, GSTM, GSTP, GSTT andGSTS. The role ofGSTM, GSTT1 orGSTP1 polymorphism in modifying the lung cancer risk may be more limited than has been so far anticipated.Although some genetic polymorphisms discussed here have not shown significant increases/decreases in risk, individuals with differing genotypes may have different susceptibilities to lung cancer. Hopefully, in future studies it will be possible to screen for lung cancer using specific biomarkers.
慢性吸入香烟烟雾是肺癌发展的一个主要危险因素。有人认为，遗传易感性可能是导致这种风险的原因，因为只有一小部分吸烟者会患上这种疾病。已经发现一些涉及香烟烟雾中致癌物的代谢激活或解毒的多态性与肺癌风险有关。许多研究都集中在不同形式代谢酶的多态性变体的分布与肺癌易感性之间的关系上。在这方面，已经讨论了涉及外源生物代谢酶的两种遗传多态性组，细胞色素 P450（CYP）和谷胱甘肽 S-转移酶（GST）。CYP 多基因超家族由 10 个亚家族（CYP1-CYP10）组成。已经在几个日本人群中报道了 CYP1A1 基因的突变纯合基因型与肺癌发展之间的正相关，但在白种人和非裔美国人中没有观察到这种相关性。CYP2D6 与肺癌之间的关系仍然存在争议和不确定。已经在 CYP2E1 基因座鉴定出几种多态性。然而，尚未确定 CYP2E1 多态性与肺癌风险之间的明确联系。其他 CYP2 同工酶在肺癌发生中的作用尚未得到充分研究。GST 形成一个由五个不同家族组成的基因超家族，分别命名为 GSTA、GSTM、GSTP、GSTT 和 GSTS。GSTM、GSTT1 或 GSTP1 多态性在改变肺癌风险方面的作用可能比迄今为止预期的更为有限。虽然这里讨论的一些遗传多态性没有显示出风险的显著增加/减少，但具有不同基因型的个体可能对肺癌的敏感性不同。希望在未来的研究中，能够使用特定的生物标志物来筛查肺癌。
