The use of biomarkers in epidemiology: the example of bladder cancer

Epidemiological studies have suggested that genetically based polymorphism for N-acetylation of arylamines might play an important role in the susceptibility to bladder cancer induction. However, these studies show large differences in the extent of such susceptibility. We have undertaken collaborative investigations (with IARC, MIT, NCI and NCTR) which couple internal dosimetry among smokers (measurement of hemoglobin and DNA adducts of arylamines) with the assessment of metabolic polymorphism. In one of these studies, hemoglobin adducts of 14 arylamines (including 2-naphthylamine and 4-aminobiphenyl) were analysed in a group of 86 subjects (smokers and non-smokers) in order to establish whether the inter-individual variability left unexplained by tobacco smoking could be attributed to differences in individual metabolic patterns. In another investigation on 100 smokers and non-smokers, metabolic polymorphism for N-acetylatransferase was assessed by measuring five different urinary metabolites of caffeine, after timed urine collection following coffee consumption. Arylamine-hemoglobin adducts were also measured. 4-Aminobiphenyl-hemoglobin adducts were found to be related to both the quantity and the type of tobacco smoked, as well as to the acetylator phenotype (independently of smoking habits).