title: 'Comparison of extremes' approach provides evidence against the modifying role of NAT2 polymorphism in lung cancer susceptibility.
abstract: 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.
authors.affiliation: Group of Molecular Diagnostics, N.N. Petrov Institute of Oncology, Pesochny-2, St-Petersburg 197758, Russian Federation.
authors.forename: Evgeniya V
authors.initials: EV
authors.lastname: Belogubova
authors.forename: Ekatherina Sh
authors.initials: ESh
authors.lastname: Kuligina
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Togo
authors.forename: Maria B
authors.initials: MB
authors.lastname: Karpova
authors.forename: Julia M
authors.initials: JM
authors.lastname: Ulibina
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Shutkin
authors.forename: Kaido P
authors.initials: KP
authors.lastname: Hanson
authors.forename: Katrin
authors.initials: K
authors.lastname: Popowski
authors.forename: Igor
authors.initials: I
authors.lastname: Mosyagin
authors.forename: Ingolf
authors.initials: I
authors.lastname: Cascorbi
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Imyanitov
mesh_terms: D000107:Acetylation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking
chemical_list: D014408:Biomarkers, Tumor; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human