NAD(P)H:quinone oxidoreductase 1 Pro187Ser polymorphism and expression do not cosegregate with clinico-pathological characteristics of human mammary tumors

Abstract

Objective: The aim of this study was to further clarify the recently reported role of NAD(P)H:quinone oxidoreductase 1 (NQO1) as a strong prognostic and predictive factor in breast cancer.

Methods: NQO1 transcript levels were monitored in mammary tumors by real-time polymerase chain reaction. NQO1 protein levels were immunohistochemically determined in formalin-fixed paraffin-embedded tissues. NQO1 polymorphism (Pro187Ser, rs1800566) was also assessed. Evaluation (N=52) and validation (N=53) sets were analyzed subsequently.

Results: Carriers of variant NQO1-Ser allele had significantly more frequently NQO1-negative protein expression (P=0.001) in both sets. NQO1 transcript levels in samples with negative protein expression were significantly lower than in those with positive NQO1 protein expression (P=0.007) in both sets. Patients with stages 0/I/II had more often positive NQO1 protein expression than patients with stages III/IV (P=0.022) in the evaluation set. Significant association between NQO1 protein expression and TP53 protein status was also found (P=0.037). However, both associations were not replicated by analysis of the validation set. Analysis of both sets combined did not show significant association of NQO1 protein expression either with stage (P=0.231) or with TP53 protein status (P>0.999). Thus, the results observed in the evaluation set were effects of small sample size.

Conclusion: The role of NQO1 in human mammary gland carcinogenesis does not seem to be directly associated with classical clinico-pathological factors.