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An Allele-Specific Polymerase Chain Reaction Method for the Determination of the D85Y Polymorphism in the Human UDPGlucuronosyltransferase 2B15 Gene in a Case-Control Study of Prostate Cancer

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Abstract

Background: UDP-glucuronosyltransferase 2B15 (UGT2B15) catalyzes the inactivation of dihydrotestosterone (DHT) by forming the DHT-glucuronide and is expressed in normal and hyperplastic prostate tissue. Alterations in the activity of this enzyme could be a major contributing factor to the bioavailability of androgens in target tissue such as the prostate.

Methods: A polymorphism (D85 to Y85) has been identified in the UGT2B15 gene1 that results in a 50% reduction in enzyme activity. Previously, detection of the polymorphic nucleotide has required direct sequencing. We have developed and validated an allele-specific polymerase chain reaction (PCR) assay to identify the polymorphic base pair in the UGT2B15 gene. This assay was used to examine the distribution of the UGT2B15 polymorphism in a small case-control group (64 cases and 64 controls) from a prostate cancer study.

Results: The results of this analysis show that prostate cancer patients were significantly more likely to be homozygous for the lower activity D85 UGT2B15 allele than control individuals (41% versus 19%, respectively, odds ratio 5 3.0 (95% confidence intervals 1.3– 6.5)).

Conclusions: These results suggest that individuals who are homozygous for the lower activity allele may be at increased risk for developing prostate cancer.

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Authors and Affiliations

  1. Department of Surgery, University of Arkansas for Medical Sciences, 4301 W. Markham St., Slot 725, Little Rock, AR, 72205

    Stewart L. MacLeod PhD, Susan Nowell MS, Jason Plaxco BS & Nicholas P. Lang MD

  2. Central Arkansas Veterans Healthcare System, Little Rock, Arkansas

    Nicholas P. Lang MD

Authors
  1. Stewart L. MacLeod PhD
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  2. Susan Nowell MS
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  3. Jason Plaxco BS
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  4. Nicholas P. Lang MD
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Correspondence to Stewart L. MacLeod PhD.

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MacLeod, S.L., Nowell, S., Plaxco, J. et al. An Allele-Specific Polymerase Chain Reaction Method for the Determination of the D85Y Polymorphism in the Human UDPGlucuronosyltransferase 2B15 Gene in a Case-Control Study of Prostate Cancer. Ann Surg Oncol 7, 777–782 (2000). https://doi.org/10.1007/s10434-000-0777-3

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  • DOI: https://doi.org/10.1007/s10434-000-0777-3

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