Dragani T A, Manenti G, Pierotti M A
Divisione di Oncologia Sperimentale A Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Ann Ist Super Sanita. 1996;32(1):145-50.
Inherited predisposition to lung tumor development appears to be a complex genetic trait, in humans as well as in experimental animals. In humans, tobacco smoking represents the main risk factor for lung tumors. Familial clusterings of lung cancer cases are rare, although affected sib pairs are reported. However, several studies have reported an increased risk of lung cancer in first degree relatives of lung cancer patients, as compared with appropriate controls. Inheritence of particular alleles of genes or phenotypes for drug metabolizing enzymes are also associated with an increased lung cancer risk. In experimental models, murine inbred strains with high genetic predisposition to lung cancer are available, as well as resistant strains. A major locus affecting inherited predisposition to lung cancer in mice has been mapped on chromosome 6, near the Kras2 gene. The locus, pulmonary adenoma susceptibility 1 (Pas1) derives from the A/J strain. Additional "minor" loci have also been mapped. Dominant lung tumor resistance loci have also demonstrated in the mouse genome. Therefore, evidence for polygenic inheritance of predisposition to lung cancer is demonstrated in the mouse model, and it is strongly suggested for human lung cancer.
在人类以及实验动物中，肺癌发生的遗传易感性似乎是一种复杂的遗传特征。在人类中，吸烟是肺癌的主要风险因素。肺癌病例的家族聚集现象很少见，尽管有报道称存在患病的同胞对。然而，几项研究报告称，与适当的对照组相比，肺癌患者的一级亲属患肺癌的风险增加。药物代谢酶的特定基因等位基因或表型的遗传也与肺癌风险增加有关。在实验模型中，有对肺癌具有高遗传易感性的小鼠近交系，以及抗性品系。一个影响小鼠肺癌遗传易感性的主要基因座已定位在6号染色体上，靠近Kras2基因处。该基因座，即肺腺瘤易感性1（Pas1），源自A/J品系。其他“次要”基因座也已定位。在小鼠基因组中也已证明存在显性肺癌抗性基因座。因此，在小鼠模型中证明了肺癌易感性多基因遗传的证据，并且强烈提示人类肺癌也存在这种情况。
