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Polymorphic variants in alpha-methylacyl-CoA racemase and prostate cancer

  1. Author:
    Daugherty, S. E.
    Shugart, Y. Y.
    Platz, E. A.
    Fallin, M. D.
    Isaacs, W. B.
    Pfeiffer, R. M.
    Welch, R.
    Huang, W. Y.
    Reding, D.
    Hayes, R. B.

  2. Author Address

    Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Johns Hopkins Sch Med, James Buchanan Brady Urol Inst, Dept Urol, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr, Johns Hopkins Med Institut, Baltimore, MD USA. SAIC Frederick Inc, Adv Technol Program, Frederick, MD USA. Marshfield Clin Res Fdn, Marshfield, WI USA.;Daugherty, SE, Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.;daughers@mail.nih.gov
    1. Year: 2007
    2. Date: Oct
  2. Journal: Prostate
    1. 67
    2. 14
    3. Pages: 1487-1497
  4. Type of Article: Article
  5. ISSN: 0270-4137
  1. Abstract:

    BACKGROUND. Alpha-methylacyl-CoA racemase (AMACR), which prepares branched chain fatty acids to be metabolized for energy and is implicated in the activation of the COX-inhibiting form of ibuprofen, is overexpressed in prostate cancer and its precursor lesions. Significant differences in AMACR allele frequencies have been reported for hereditary prostate cancer (HPC), but the relevance of AMACR in the context of its substrates have not been studied. METHODS. We conducted a nested case-control study of 1,318 prostate cancer cases and 1,842 controls from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Five non-synonymous (nsSNP) and two intronic AMACR polymorphisms were genotyped. Conditional logistic regression models were used to evaluate the associations between the genetic variants and prostate cancer. RESULTS. Overall, prostate cancer was not related to AMACR gene variants; however, risks for prostate cancer were significantly reduced among regular ibuprofen users who carried allele variants at four nsSNP loci (M9V, D175G, S201 L, and K277E; all P-trend, < 0.05) or carried the TGTGCG haplotype (OR = 0.65; 95% Cl 0.44-0.97). No AMACR-related associations were noted among nonregular ibuprofen users (all P-interaction > 0.33). CONCLUSION. AMACR gene variants were unrelated to prostate cancer overall in this study. The protective associations observed among ibuprofen users suggest that AMACR gene variants may enhance the chemopreventive effects of ibuprofen on prostate cancer risk.

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  2. DOI: 10.1002/pros.20635
  3. View record in Web of Science®
  4. WOS: 000250035500001

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