Vineis P, Martone T
Dipartimento di Scienze Biomediche e Oncologia Umana, Università degli Studi, Turin, Italy.
Ann Ist Super Sanita. 1996;32(1):21-7.
In order to ascertain the role of arylamines in the induction of bladder cancer in smokers, and to assess the contribution of the metabolic phenotype to cancer risk, studies of molecular epidemiology have been conducted. A number of investigations have reported that "slow" acetylators are at higher risk of bladder cancer, especially subgroups occupationally exposed to arylamines. We present the results of studies that investigated markers of both internal dose (hemoglobin adducts, urinary mutagenicity), and genetically determined susceptibility (metabolic polymorphism) among smokers. Levels of ABP-hemoglobin adducts were elevated in smokers of black (air-cured) tobacco compared to smokers of blond tobacco, and "slow" acetylators showed higher levels than "fast" acetylators. Further, a combination of slow acetylator and fast oxidizer phenotype was associated with the highest level of ABP-hemoglobin adduct. Thus the determination of both phenotypes may allow to better predict the risk of bladder cancer than using the "slow" acetylator phenotype alone. Further investigations in this field will consider the occurrence of mutational spectra (hotspots) in relevant genes (e.g.p53 or p16) to ascertain whether tobacco-related carcinogens induce specific mutations.
为了确定芳基胺在吸烟者膀胱癌诱发中的作用，并评估代谢表型对癌症风险的影响，已经开展了分子流行病学研究。多项调查报道称，“慢”乙酰化者患膀胱癌的风险更高，尤其是职业性接触芳基胺的亚组人群。我们展示了相关研究结果，这些研究调查了吸烟者体内内剂量标志物（血红蛋白加合物、尿液致突变性）以及基因决定的易感性（代谢多态性）。与吸食浅色烟草的吸烟者相比，吸食黑色（晾制）烟草的吸烟者体内ABP-血红蛋白加合物水平升高，且“慢”乙酰化者的水平高于“快”乙酰化者。此外，“慢”乙酰化者和“快”氧化者表型的组合与ABP-血红蛋白加合物的最高水平相关。因此，与仅使用“慢”乙酰化者表型相比，同时测定这两种表型可能能更好地预测膀胱癌风险。该领域的进一步研究将考虑相关基因（如p53或p16）中突变谱（热点）的出现情况，以确定烟草相关致癌物是否会诱发特定突变。
