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    NAD(P)H:Quinone oxidoreductase-1 C609T polymorphism analysis in human superficial bladder cancers: relationship of genotype status to NQO1 phenotype and clinical response to Mitomycin C.

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    Publication date
    2004
    Author
    Basu, Saurajyoti
    Brown, John E.
    Flannigan, G. Michael
    Gill, Jason H.
    Loadman, Paul M.
    Martin, Sandie W.
    Naylor, Brian
    Puri, Rajiv
    Scally, Andy J.
    Seargent, Jill M.
    Shah, Tariq K.
    Phillips, Roger M.
    Show allShow less
    Keyword
    NAD(P)H:Quinone oxidoreductase-1 C609T
    Mitomycin C (MMC)
    Polymorphism analysis
    Human superficial bladder cancers
    Peer-Reviewed
    n/a
    
    Metadata
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    Abstract
    NAD(P)H:Quinone oxidoreductase-1 (NQO1) has been implicated in the bioreductive activation of the clinically active anticancer drug Mitomycin C (MMC) and a polymorphic variant of NQO1 which lacks functional enzyme activity (NQO1*2) has been linked with poor survival in patients treated with MMC. The relationship between NQO1 activity and cellular response to MMC is however controversial and the aim of this study was to determine whether the response of bladder cancer patients to MMC can be forecast on the basis of NQO1*2 genotype status. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue from 148 patients with low to intermediate grade (G1/G2) superficial (Ta/T1) bladder cancers and NQO1*2 genotype status determined by PCR-RFLP. NQO1*2 genotype status was retrospectively compared with clinical response to intravesical administered MMC with the primary end-point being time to first recurrence. NQO1 phenotype was determined by immunohistochemistry. Of the 148 patients genotyped, 85 (57.4%) were NQO1*1 (wild-type), 59 (39.8%) were NQO1*1/*2 (heterozygotes) and 4 (2.7%) were NQO1*2/*2. No NQO1 protein expression was detected in NQO1*2/*2 tumours. A broad spectrum of NQO1 protein expression existed in tumours genotyped as NQO1*1 and NQO1*1/*2 although tumours with NQO1*1 typically expressed higher NQO1 protein. A poor correlation existed between NQO1*2 genotype status and clinical response to MMC. The results of this retrospective study suggest that tailoring MMC therapy to individual patients with superficial bladder cancer on the basis of NQO1 genotype status is unlikely to be of clinical benefit.
    URI
    http://hdl.handle.net/10454/6401
    Version
    published version paper
    Citation
    Basu, S., Brown, J. E., Flannigan, G. M., Gill, J. H., Loadman, P. M., Martin, S. W., Naylor, B., Puri, R., Scally, A. J., Seargent, J. M., Shah, T. and Phillips, R. M. (2004) NAD(P)H:Quinone oxidoreductase-1 C609T polymorphism analysis in human superficial bladder cancers: relationship of genotype status to NQO1 phenotype and clinical response to Mitomycin C. International Journal of Oncology, 25 (4): 921-7.
    Link to publisher’s version
    http://www.spandidos-publications.com/ijo/25/4/921/abstract
    Type
    Article
    Collections
    Health Studies Publications

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