Spitz M R, Bondy M L
Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston.
Cancer. 1993 Aug 1;72(3 Suppl):991-5. doi: 10.1002/1097-0142(19930801)72:3+<991::aid-cncr2820721307>3.0.co;2-5.
For any given level of exposure to a carcinogen, only a proportion of exposed individuals will develop cancer. Interindividual differences in susceptibility at some stage of the carcinogenic process must be postulated. One contributing factor is variation in the activity of metabolizing enzymes responsible for conversion of procarcinogens to proximate carcinogens. There is also a wide spectrum of DNA repair capability within the general population. At one end are the genetic instability syndromes characterized by extreme sensitivity to carcinogenic exposures and high rates of cancer in homozygotes of these traits. Less extreme differences in mutagen sensitivity can be demonstrated by a quantitative assay of chromosome breaks induced by in vitro mutagen exposure. Two case-control studies of patients with previously untreated upper aerodigestive tract cancers have demonstrated mutagen sensitivity to be an independent risk factor for the disease after controlling for the effects of tobacco and alcohol. Mutagen sensitivity also may have prognostic relevance. There was a fourfold elevated risk of developing multiple primary cancers in mutagen-sensitive patients. There are also data suggestive of familial aggregation of cancer in first-degree relatives of mutagen-sensitive patients (twofold risk for having one first-degree relative with cancer and sixfold risk for having two or more relatives with cancer). The preventive implications of identifying markers of carcinogen sensitivity are manifold.
对于任何给定水平的致癌物暴露，只有一部分暴露个体才会患癌症。必须假定在致癌过程的某个阶段个体易感性存在差异。一个促成因素是负责将前致癌物转化为近致癌物的代谢酶活性的变化。在普通人群中，DNA修复能力也存在很大差异。一端是遗传不稳定综合征，其特征是对致癌暴露极度敏感，这些性状的纯合子患癌率很高。通过对体外诱变剂暴露诱导的染色体断裂进行定量测定，可以证明诱变敏感性存在不太极端的差异。两项针对未经治疗的上消化道癌症患者的病例对照研究表明，在控制烟草和酒精的影响后，诱变敏感性是该疾病的一个独立危险因素。诱变敏感性也可能与预后相关。诱变敏感的患者患多发性原发性癌症的风险增加了四倍。也有数据表明，诱变敏感患者的一级亲属中癌症存在家族聚集现象（有一个患癌一级亲属的风险为两倍，有两个或更多患癌亲属的风险为六倍）。识别致癌物敏感性标志物的预防意义是多方面的。
