N-Acetyltransferase-2 and Medical History in Bladder Cancer Cases with a Suspected Occupational Disease (BK 1301) in Germany

Abstract

In 187 bladder cancer cases reported to the employers' liability insurance association in Germany as suspected cases of an occupational disease produced by aromatic amines, N- acetyltransferase-2 (NAT2) activity status, occupational exposure data, period of latency, and clinical parameters were determined. In 83 out of 187 cases surveyed within the period 1991-1999, the NAT2 acetylator status was investigated by determining the molar ratio of an acetylated and a nonacetylated caffeine metabolite in urine (phenotyping) and/or by NAT2 genotyping according to standard polymerase chain reaction (PCR) protocol. The proportion of slow NAT2 acetylators in the surveyed 83 bladder cancer cases was 67%. In the entire group of surveyed 187 cases, mean duration of exposure was 17.6 yr and mean period of latency was 34.7 yr. Occupational exposures to potential bladder carcinogens were observed in 73 occupations, including chemical industry (25%), and occupations as a painter and/or varnisher (23%) were most often encountered. In 12% of the surveyed bladder cancer cases, a second primary malignancy was observed. The NAT2 distribution observed in the 83 cases is comparable to the proportion in 40 occupationally exposed bladder cancer cases in a Department of Urology located close to a former German production site of benzidine-based azo dyes, but higher than in most studies involving NAT2 genetic status in bladder cancer cases.

Study of risk factors for development of urinary bladder cancer in patients in Urmia; a single-center study by logit regression approach

“…of being exposed to this material drastically increases. In the developed countries due to strict regulations, the incidence of urinary bladder cancer is minimized (7).…”

Risk Factors for Urothelial Cancers

“…Karsinojenik aromatik aminlere 10 yıl ve daha fazla maruziyet sonrası risk anlamlı derecede artmaktadır. Genellikle geçen ortalama süre 30 yılı aşkındır (10,11). Bu konuda farkındalığın oluşması gerekli önlemlerin alınmasının yolunu açmıştır.…”

Clarifying haplotype ambiguity of NAT2 in multi-national cohorts

“…Since then, numerous studies have analysed the impact of inter-individual variation in the acetylation capacity on drug efficacy and side effects as well as on cancer susceptibility especially focussing on exposure to carcinogenic NAT2 substrates such as aromatic and heterocyclic amines (2,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). The role of NAT2 in cancer development is debated for a number of tumours (for review see 22); with respect to bladder cancer large studies and meta-analyses show an increased risk for slow acetylators, in particular, if they were exposed to aromatic amines or smoking (6,15,23,24).…”