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Genetic polymorphism of drug-metabolising enzymes such as  NQO1, SULT1A1, EPHX1 , and  NAT2  alters its activity which hampers the detoxification and disposal of chemotherapeutic compounds. Thus, in the present study, we have comprehensively investigated the associations between SNPs of the Phase II detoxifying genes and its relationship towards platinum-induced toxicity of lung cancer patients.NQO1  (609 C &gt; T),  SULT1A1  (Arg 213  His),  EPHX1  (Tyr 113 His, His 139 Arg), and  NAT2  (481 C &gt; T, 803 A &gt; G, 590 G &gt; A, 857 G &gt; A) were evaluated in our study for their associated adverse events caused due to the administration of platinum-based chemotherapy to the lung cancer patients.For  NQO1  609 C &gt; T polymorphism, the  TT  genotype showed reduced risk of constipation (OR = 0.10,  p  = 0.04) and anorexia (OR = 0.15,  p  =  0.03 ). For  SULT1A1 Arg 213 His,  heterozygous genotype ( Arg/His ) (AOR = 0.38,  p  =  0.006 ) and combined genotype ( Arg/His + His/His ) were not associated with increased risk of nephrotoxicity (AOR = 0.38,  p  =  0.004 ). For  NAT2,  heterozygous ( NAT2*4/*6 ) and combined genotypes ( NAT2*4/*4+*4/*6 ) for  NAT2*6  polymorphism exhibit 2.4 folds ( p  =  0.005 ), and two-folds ( p  =  0.01 ) increased risk of hematological toxicity. The heterozygous (AOR = 0.45,  p  =  0.004 ) and variant genotype (AOR = 0.39,  p  =  0.02 ) for  NAT2*5C  had decreased risk for hematological toxicity. The heterozygous genotype for  NAT2*7  polymorphism showed two-fold increased risk for developing thrombocytopenia.This study provides association of  NAT2  polymorphic variants in predicting haematological toxicity. Genetic polymorphism of drug-metabolising enzymes such as  NQO1, SULT1A1, EPHX1 , and  NAT2  alters its activity which hampers the detoxification and disposal of chemotherapeutic compounds. Thus, in the present study, we have comprehensively investigated the associations between SNPs of the Phase II detoxifying genes and its relationship towards platinum-induced toxicity of lung cancer patients. NQO1  (609 C &gt; T),  SULT1A1  (Arg 213  His),  EPHX1  (Tyr 113 His, His 139 Arg), and  NAT2  (481 C &gt; T, 803 A &gt; G, 590 G &gt; A, 857 G &gt; A) were evaluated in our study for their associated adverse events caused due to the administration of platinum-based chemotherapy to the lung cancer patients. For  NQO1  609 C &gt; T polymorphism, the  TT  genotype showed reduced risk of constipation (OR = 0.10,  p  = 0.04) and anorexia (OR = 0.15,  p  =  0.03 ). For  SULT1A1 Arg 213 His,  heterozygous genotype ( Arg/His ) (AOR = 0.38,  p  =  0.006 ) and combined genotype ( Arg/His + His/His ) were not associated with increased risk of nephrotoxicity (AOR = 0.38,  p  =  0.004 ). For  NAT2,  heterozygous ( NAT2*4/*6 ) and combined genotypes ( NAT2*4/*4+*4/*6 ) for  NAT2*6  polymorphism exhibit 2.4 folds ( p  =  0.005 ), and two-folds ( p  =  0.01 ) increased risk of hematological toxicity. The heterozygous (AOR = 0.45,  p  =  0.004 ) and variant genotype (AOR = 0.39,  p  =  0.02 ) for  NAT2*5C  had decreased risk for hematological toxicity. The heterozygous genotype for  NAT2*7  polymorphism showed two-fold increased risk for developing thrombocytopenia. This study provides association of  NAT2  polymorphic variants in predicting haematological toxicity.

xenobiotica

Predictive role of polymorphic variants of phase II drug metabolising enzyme in modulating toxicity in North Indian lung cancer patients undergoing chemotherapy