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Association of genotypes of carcinogen‐activating enzymes, phenol sulfotransferase SULT1A1 (ST1A3) and arylamine N‐acetyltransferase NAT2, with urothelial cancer in a Japanese population
Author(s) -
Ozawa Shogo,
Katoh Takahiko,
Inatomi Hisato,
Imai Hirohisa,
Kuroda Yoshiki,
Ichiba Masayoshi,
Ohno Yasuo
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10728
Subject(s) - sulfotransferase , carcinogen , genotype , arylamine n acetyltransferase , allele , cancer , biology , enzyme , population , medicine , chemistry , genetics , sulfation , biochemistry , gene , environmental health
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.