GENETIC-POLYMORPHISM OF N-ACETYLTRANSFERASES, GLUTATHIONE-S-TRANSFERASE M1 AND NAD(P)H-QUINONE OXIDOREDUCTASE IN RELATION TO MALIGNANT AND BENIGN PANCREATIC DISEASE RISK

Carcinogens present in cigarette smoke and diet have been associated w ith pancreatic cancer. We hypothesized that heterocyclic and aromatic amines implicated in these exposures could be involved as causative ag ents and that therefore genetic variation in enzymes metabolizing thes e carcinogens could modify the risk of developing malignant and benign pancreatic disease, The effect of the genetic polymorphism of acetylt ransferases (NAT1 and NAT2), glutathione S-transferase M1 (GSTM1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) on the risk of pancreatic dis eases (cancer, pancreatitis) was examined in a case-control study, PCR -based assays were used for genotype analysis of genomic DNA from whol e blood cells, Samples collected from Caucasian patients with diagnose d pancreatic cancer (n = 81), with non-alcoholic (n = 41) and alcoholi c pancreatitis (n = 73) and from asymptomatic control subjects (n = 78 ) were analysed, The prevalence of GSTM1 null genotype and of NAT2 fas t and slow acetylator genotypes and the distribution of frequencies fo r NQO1 genotypes did not differ in subjects with pancreatic diseases v s controls. For NAT1 slow acetylators a non-significant excess (P = 0. 18) was found among pancreatic cancer cases vs controls. There was a s ignificant over-representation of the GSTM1 AB or B genotype in all pa ncreatic disease cases combined (OR = 2.6; P < 0.05). When concurrent controls were pooled with literature controls (n = 1427), OR was 1.4 ( P = 0.08), The results of this study, requiring confirmation, suggest that the polymorphism of GSTM1 and NAT1 enzymes may be associated with a modest increase in susceptibility to pancreatic disease. (C) 1998 L ippincott-Raven Publishers.