Clinical significance of a NAD(P)H: quinone oxidoreductase 1 polymorphism in patients with disseminated peritoneal cancer receiving intraperitoneal hyperthermic chemotherapy with mitomycin C

摘要: Recent data indicate that NAD(P)H: quinone oxidoreductase 1 (NQO1) is important in the activation of mitomycin C. A polymorphism human NQO1 (609C>T) associated with diminished activity. The purpose our study was to determine effect 609C>T on tumor activity and overall survival patients disseminated peritoneal cancer receiving intraperitoneal C therapy. Patients gastrointestinal or other origin were eligible. Following aggressive surgical debulking, administered a 2-h heated (40.5 degrees C) perfusion determined tissue obtained during surgery genotyped for C609T using polymerase chain reaction-based method. major response variable monitored trial survival. Of 117 polymorphism, 67% wild-type (WT), 31% heterozygous (HE), 2% homozygous mutant (HM). In tissue, mean activities from WT (n = 14) HE 5) 794 +/- 603 70 133.1 nmol/min/mg protein respectively (P 0.006). Significant differences between versus HE/HM genotypes noted optimally debulked (R0/R1) (43.6+ months, median not yet reached 23 months respectively, P 0.037) carcinomatosis colonic (18.2 11.5 0.050). These results significantly reduced subsets hyperthermic