Molecular epidemiology of bladder cancer.

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.