'Comparison of extremes' approach provides evidence against the modifying role of NAT2 polymorphism in lung cancer susceptibility.
Cancer Lett
; 221(2): 177-83, 2005 Apr 28.
Article
en En
| MEDLINE
| ID: mdl-15808403
NAT2 (arylamine N-acetyltransferase 2) polymorphism, being a key determinant of individual variations in acetylation capacity, is suspected to modify the risk of carcinogen-related malignancies. As tobacco smoke and other inhaled hazards contain a variety of NAT2 substrates, the relationship between NAT2 phenotype and lung cancer (LC) risk has been a subject of intensive research, however different case-control studies produced controversial data. In the present report, we employed a novel 'comparison of extremes' approach, i.e. we compared the distribution of NAT2 genotypes in lung cancer patients (LC, n=178) not only to the population controls (healthy donors (HD), n=364), but also to the subjects with a putative cancer-resistant constitution (elderly tumor-free smokers and non-smokers (ED), n=351). Frequencies of homozygous rapid, heterozygous rapid and slow acetylators were 6, 39 and 56% in LC, 8, 32 and 60% in HD, and 6, 35 and 59% in ED, respectively. Comparison of the NAT2 genotype frequencies between affected and non-affected individuals did not reveal any statistical deviations, irrespectively of smoking history, gender, age, or histological type of LC. Adjusted odds ratio for rapid vs. slow acetylators was 1.12 (95% confidence intervals (CI): 0.73-1.74) comparing LC vs. HD, and 1.10 (95% CI: 0.74-1.62) comparing LC vs. ED. Similar distribution of NAT2 acetylator genotypes both in tumor-prone and in tumor-resistant groups suggests that, despite the presence of NAT2 carcinogenic substrates in tobacco smoke, NAT2 polymorphism does not play a noticeable role in lung cancer susceptibility.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
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Arilamina N-Acetiltransferasa
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Predisposición Genética a la Enfermedad
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Neoplasias Pulmonares
Tipo de estudio:
Etiology_studies
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Observational_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Lett
Año:
2005
Tipo del documento:
Article
Pais de publicación:
Irlanda