In:
International Journal of Cancer, Wiley, Vol. 102, No. 4 ( 2002-12), p. 418-421
Abstract:
Carcinogenic aromatic amines such as 4‐aminobiphenyl, which is contained in tobacco smoke, are one of the causal factors of urothelial epithelial cancers. 4‐Aminobiphenyl has been shown to be bioactivated through N ‐hydroxylation by hepatic cytochrome (CYP) 1A2 and subsequently through O ‐sulfation and O ‐acetylation by phenol sulfating sulfotransferase, ST1A3 (SULT1A1), and arylamine N ‐acetyltransferase, NAT2, respectively. In a case‐control study for urothelial epithelial cancers, low activity alleles of NAT2 are overall high‐risk alleles (OR 2.11; 95% CI 1.08–4.26). Wild‐type ST1A3*1 ( 213 Arg) alleles were slightly overrepresented in nonsmoking urothelial cancer patients (82.6% vs. 69.7%) and in smoking cancer patients (76.7% and 74.3%) compared to a variant ST1A3*2 ( 213 His) allele. In combination of ST1A3 and NAT2 genotypes for analyses of urothelial cancer risk, the highest OR of 2.45 (95% CI 1.04–5.98) was obtained with ST1A3*1 and NAT2 slow genotype among the 4 combinations. Recombinant ST1A3*1 enzyme showed a tendency of catalyzing higher in vitro 3′‐phosphoadenosine 5′‐phosphosulfate‐dependent DNA adduct formation than ST1A3*2 (2.84 ± 0.49 and 2.22 ± 0.11 adducts/10 8 nucleotides). Combined analyses of different alleles of carcinogenic aromatic amine‐activating phase II enzymes were applied to urothelial cancer risk for the first time and showed the highest risk combination of ST1A3 and NAT2 alleles. © 2002 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
0020-7136
,
1097-0215
Language:
English
Publisher:
Wiley
Publication Date:
2002
detail.hit.zdb_id:
218257-9
detail.hit.zdb_id:
1474822-8
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