PT - JOURNAL ARTICLE AU - Cascorbi, Ingolf AU - Brockmöller, Jürgen AU - Mrozikiewiz, Przemyslaw M. AU - Bauer, Steffen AU - Loddenkemper, Robert AU - Roots, Ivar TI - Homozygous Rapid Arylamine <em>N</em>-Acetyltransferase (<em>NAT2</em>) Genotype as a Susceptibility Factor for Lung Cancer DP - 1996 Sep 01 TA - Cancer Research PG - 3961--3966 VI - 56 IP - 17 4099 - http://cancerres.aacrjournals.org/content/56/17/3961.short 4100 - http://cancerres.aacrjournals.org/content/56/17/3961.full SO - Cancer Res1996 Sep 01; 56 AB - The polymorphic arylamine N-acetyltransferase (NAT2) is supposed to be a susceptibility factor for certain malignancies. A phenotyping study in 389 lung cancer patients revealed a similar distribution of rapid and slow acetylators by the caffeine test to that in 657 reference subjects (odds ratio, 1.05; 95% confidence limits, 0.81, 1.36; not significant). A separate group of 155 lung cancer patients was studied by genotyping NAT2 and was compared with a matched reference group of 310 unrelated patients and with 278 healthy volunteers. The NAT2 genotype was characterized by PCR-RFLP at nucleotide positions 191, 282, 341, 481, 590, 803, and 857. For evaluation of nucleotide 341, a 3′-mismatch primer was used. Homozygous wild-type genotypes NAT2*4/*4 were confirmed by DNA sequencing. Genotypes for rapid acetylation amounted to 43.9% among lung cancer and 41.6% among reference patients (odds ratio, 1.10 95% confidence limits, 0.73, 1.65; not significant). Discrimination into homozygous and heterozygous carriers of allele NAT2*4 revealed a distinct overrepresentation of NAT2*4/*4 genotypes amid lung cancer patients (odds ratio, 2.36; 95% confidence limits, 1.05, 5.32; P = 0.018). Logistic regression analysis considering sex, age, and smoking provided an odds ratio of 3.04 (95% confidence limits, 1.37, 6.75; P = 0.003). Hence, carriers of the NAT2*4/*4 genotype, with its especially high acetylation capacity, are at significantly increased risk to lung cancer. ©1996 American Association for Cancer Research.