The rapid arylamine N-acetyltransferase (NAT2) genotype: A hereditary susceptibility factor for laryngeal cancer

Background. Recent interest has focused on heritable differences in foreign compound metabolizing enzymes as host factors of cancer risk. The metabolic step of N-acetylation plays a significant role in biotransformation of various drugs, precarcinogens, and other xenobiotics with a primary amine or a hydrazine structure. Arylamines contained in cigarette smoke may be metabolized by the polymorphic arylamine N-acetyltransferase (NAT2). Further biotransformation involving the phase-I enzyme cytochrome P4501A2, results in highly reactive arylnitrenium ions which may affect the DNA. Methods. A total of 179 laryngeal cancer patients were genotyped for the acetylation type and compared with 358 reference subjects, matched by age and gender. In all, seven mutations of the intronless NAT2-gene from lymphocyte DNA were characterized by PCR-RFLP with restriction enzymes FokI, KpnI, TaqI, DdeI, and BamHI for mutations at position 191, 282, 341, 590, 803, and 857 nt, respectively. Results. Altogether, 86 (48.1%) individuals with rapid genotypes occurred among laryngeal cancer patients, whereas 149 (41.6%) were found in the reference group (odds ratio = 1.30, 95%-confidence limits 0.89-1.89, p = 0.093). Particularly, an overrepresentation of 13 (7.3%) homozygous rapid genotypes (NAT2*4/*4 and NAT2*4/*12A) amid laryngeal cancer patients vs. 15 (4.2%) among controls was detected (odds ratio = 1.95, 95%-confidence limits 0.82-4.58, p = 0.072). Conclusions. The data suggest that high acetylation rates seem to be a susceptibility factor, promoting risk of initiation of squamous cell carcinoma of the larynx. This is in line with findings among lung cancer patients.