GENOTYPING OF THE POLYMORPHIC N-ACETYLTRANSFERASE (NAT2) AND LOSS OF HETEROZYGOSITY IN BLADDER-CANCER PATIENTS

Acetylation is one of the major routes in metabolism and detoxificatio n of a large number of drugs: chemicals and carcinogens, Slow acetylat ors are said to be more susceptible to developing bladder cancer and b ecause of investigations about tumor risk based on phenotyping procedu res, it was our aim to study the distribution of allelic constellation s of the N-acetyltransferase (NAT2) bq genotyping patients with bladde r cancer. We analysed NAT2 gene of blood and tumor DNA from 60 patient s with primary bladder cancer and DNA of blood samples from 154 health y individuals. Using ASO-PCR/RFLP techniques we identified 70% of pati ents with bladder cancer (n = 42) to be slow acetylators while genotyp ing of controls resulted in 61% with slow acetylators (n = 94). In add ition, dividing bladder cancer patients in males and females the genot ype NAT25B/NAT2*6A occured with much higher frequencies in males (OR = 4, 95%: CI = 1.8-8.9), Furthermore, investigating bladder cancer tis sues we could detect loss of heterozygosity (LOH) in slow and rapid ac etylator genotypes. In eleven out of 60 tumor samples (18.3%) we obser ved allelic loss at the NAT2 locus while in control DNA of blood from the same patients both alleles were still detectable.