INCREASED FREQUENCY OF A NULL-ALLELE FOR NAD(P)H - QUINONE OXIDOREDUCTASE IN PATIENTS WITH UROLOGICAL MALIGNANCIES

The NQ01 locus on chromosome 16q2.2 encodes NAD(P)H:quinone oxidoreduc tase, an enzyme implicated in detoxication and protection against redo x cycling, Two alleles have been identified in the human population, t he rarer one, termed the null-allele, coding for a nonfunctional enzym e, Since lack of NQOR activity has been suggested to increase suscepti bility to certain cancers, the distribution of the two alleles was det ermined by polymerase chain reaction-restriction fragment length polym orphism analysis in patients with renal cell carcinoma (n = 131) and u rothelial carcinoma (n = 99) compared with a normal population (n = 26 0), Allele distribution in the normal population followed a Hardy-Wein berg distribution with frequencies of 0.867 for the major allele and 0 .133 for the null-allele. Increased frequencies of the null-allele wer e found in the tumour patient groups (0.191 and 0.182, respectively) d ue to an increased number of both homo- and heterozygotes. The odds ra tios for homozygous null-allele vs, wild-type genotypes were 1.7 and 3 .6 for renal cell carcinoma and urothelial carcinoma, respectively, Th ese data are compatible with the assumption that diminished activity o f NQOR in some individuals increases susceptibility to certain cancers .