Homozygous rapid arylamine N-acetyltransferase (NAT2) genotype as a susceptibility factor for lung cancer.
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 over-representation 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.
Cascorbi
I
I
Institute of Clinical Pharmacology, University Clinic Charité, Humboldt University of Berlin, Germany. cascorbi@rz.charite.hu-berlin.de
Brockmöller
J
J
Mrozikiewicz
P M
PM
Bauer
S
S
Loddenkemper
R
R
Roots
I
I
D000107:Acetylation; D000368:Aged; D000369:Aged, 80 and over; D000588:Amines / Q000378:metabolism; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001483:Base Sequence; D004198:Disease Susceptibility; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012737:Sex Factors; D012907:Smoking
D000588:Amines; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human