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Pharmacogenet Genomics. 2009 Jul;19(7):505-12. doi: 10.1097/FPC.0b013e32832cf9cf.

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

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1
Laboratory of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic.

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.

PMID:
19494791
DOI:
10.1097/FPC.0b013e32832cf9cf
[Indexed for MEDLINE]
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