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Titolo:
Association of NAT1 and NAT2 polymorphisms to urinary bladder cancer: Significantly reduced risk in subjects with NAT1*10
Autore:
Cascorbi, I; Roots, I; Brockmoller, J;
Indirizzi:
Univ Greifswald, Inst Pharmakol, D-17487 Greifswald, Germany Univ Greifswald Greifswald Germany D-17487 , D-17487 Greifswald, Germany Humboldt Univ, Charite, Med Ctr, Inst Clin Pharmacol, D-10098 Berlin, Germany Humboldt Univ Berlin Germany D-10098 Pharmacol, D-10098 Berlin, Germany Univ Gottingen, Ctr Pharmacol, D-37075 Gottingen, Germany Univ Gottingen Gottingen Germany D-37075 col, D-37075 Gottingen, Germany
Titolo Testata:
CANCER RESEARCH
fascicolo: 13, volume: 61, anno: 2001,
pagine: 5051 - 5056
SICI:
0008-5472(20010701)61:13<5051:AONANP>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
ARYLAMINE N-ACETYLTRANSFERASES; N-ACETYLTRANSFERASE-1 NAT1; SUSCEPTIBILITY FACTOR; METABOLIC-ACTIVATION; COLORECTAL ADENOMAS; GENE; ACETYLATION; GENOTYPE; SMOKING; PHENOTYPE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Cascorbi, I Univ Greifswald, Inst Pharmakol, Friedrich Loeffler Str 23D, D-17487 Greifswald, Germany Univ Greifswald Friedrich Loeffler Str 23D Greifswald Germany D-17487
Citazione:
I. Cascorbi et al., "Association of NAT1 and NAT2 polymorphisms to urinary bladder cancer: Significantly reduced risk in subjects with NAT1*10", CANCER RES, 61(13), 2001, pp. 5051-5056

Abstract

The role of hereditary polymorphisms of the arylamine N-acetyltransferase 1 (NAT1) gene in the etiology of urinary bladder cancer is controversial. NAT1 is expressed in the urothelium and may O-acetylate hydroxyl amines, particularly in subjects with low NAT2 activity. Thus, NAT1 polymorphisms may affect the individual bladder cancer risk by interacting with environmentalfactors (smoking and occupational risks) and by interacting with the NAT2 gene. We studied the frequencies of the NAT1 haplotypes *3, *4, *10, *11, *14, *15, *17, and *22 in 425 German bladder cancer patients and 343 controls by PCR-RFLP. NAT1*10 allelic frequency was lower in bladder cancer patients (15.1%) compared with controls (20.4%; P = 0.012). Genotypes that included NAT1*10 were significantly less frequent among the cases (odds ratio adjusted for age, gender, and smoking, 0.65; 95% confidence interval, 0.46-0.91; P = 0.013). Two subtypes of NAT1*11 were detected: *11A (-344T, -40T, 445A, 459A, 640G, and 1095A) and *11C (-344T, -40T, 459A, 640G, and 1095A). The allele frequency of NAT1*11 was 4.3% in the cases versus 3.9% in the controls. The rare low-active NAT1*14A was overrepresented in the cases (P = 0.026). With regard to the NAT2 genotype, our data showed: (a) a partial linkage of NAT1*10 to NAT2*4; (b) a clear underrepresentation of NAT1*10 genotypes among rapid NAT2 genotypes in the cases studied (odds ratio, 0.39; 95%confidence interval, 0.22-0.68; P = 0.001), and (c) a gene-gene-environment interaction. NAT2*'slow/NAT1*4 genotype combinations with a history of occupational exposure were 5.96 (2.96-12.0) times more frequent in cancer cases than in controls without risk occupation (P < 0.0001). Hence, our data suggest that individuals provided with NAT2*4 and NAT1*10 are at a significantly lower risk for bladder cancer, particularly when exposed to environmental risk factors.

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Documento generato il 02/04/20 alle ore 20:53:01