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NQO1*2 [NAD(P)H: quinone oxidoreductase 1] polymorphism and its influence on acute leukemia risk

Dunna NR, Anuradha C, Vure S, Sailaja K, Surekha D, Raghunadharao D, Rajappa S, Vishnupriya S

NAD (P) H: quinone oxidoreductase 1 (NQO1) is an enzyme that protects cells against mutagenicity from free radicals and toxic oxygen metabolites. The gene coding for NQO1 has polymorphism at nucleotide position 609(C-T) of the human cDNA. Heterozygous individuals (C/T) have intermediate activity and homozygotes for the variant allele (T/T) are deficient in NQO1 activity. In previous studies, genotypes conferring lower NQO1 activity have been associated with an increased risk of acute leukemia. The present study includes 297 acute leukemia cases comprising of 151 acute lymphocytic leukemia (ALL), 146 acute myeloid leukemia (AML) and 220 control samples for analysis of NQO1*2 polymorphism using PCR-RFLP method. The NQO1*2 polymorphism was significantly associated with acute leukemia development (�?2- 31.614; df-2, p - < 0.000) with respect to clinical variables. Mean WBC, Blast %, LDH levels were increased in both ALL and AML cases with TT genotype. 50% of AML cases failed to achieve complete remission towards therapy. There was significant reduction in mean DFS (Disease Free Survival) in both ALL and AML cases with TT genotype (21.18m, 8.31m). Our results suggest that TT genotype might be considered as a risk genotype for development of acute leukemia and is associated with poor prognostic markers.