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

Sarah E. Daugherty, Yin Yao Shugart, Elizabeth A. Platz, M. Daniele Fallin, William B. Isaacs, Ruth M. Pfeiffer, Robert Welch, Wen Yi Huang, Douglas Reding, Richard B. Hayes

Research output: Contribution to journalArticle

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, S201L, and K277E; all Ptrend < 0.05) or carried the TGTGCG haplotype (OR = 0.65; 95% CI 0.44-0.97). No AMACR-related associations were noted among nonregular Ibuprofen users (all Pinteraction > 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.

Original languageEnglish (US)
Pages (from-to)1487-1497
Number of pages11
JournalProstate
Volume67
Issue number14
DOIs
StatePublished - Oct 1 2007

Keywords

  • AMACR
  • Branched chain fatty acids
  • Haplotypes
  • Ibuprofen
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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    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. (2007). Polymorphic variants in α-methylacyl-CoA racemase and prostate cancer. Prostate, 67(14), 1487-1497. https://doi.org/10.1002/pros.20635