Sequence variants of alpha-methylacyl-CoA racemase are associated with prostate cancer risk: A replication study in an ethnically homogeneous population

FitzGerald, LM; Thomson, R; Polanowski, A; Patterson, B; Mckay, JD; Stankovich, J; Dickinson, JL

Author(s): FitzGerald, LM; Thomson, R; Polanowski, A; Patterson, B; Mckay, JD; Stankovich, J; Dickinson, JL;
Details: Publication Year 2008-09-15,Volume 68,Issue #13,Page 1373-1379
Journal Title: PROSTATE
Publication Type: Journal Article
Abstract: BACKGROUND. Examination of variants of the alpha-methylacyl-CoA racemase (AMACR) gene, as genetic contributors to prostate cancer risk, has been of considerable interest given the gene's recently established role as a diagnostic biomarker for prostate cancer. METHODS. The AMACR gene variants, M9V and D175G, were genotyped in a familial dataset comprising 127 cases and in a second sporadic prostate cancer dataset comprising 414 cases and 319 controls. Genotype-disease associations were examined employing the M-QLS test and unconditional logistic regression. Differences in allele frequencies were examined using the Fisher's exact test. Association between the AMACR haplotypes and prostate cancer risk was also investigated using haplo.score. RESULTS. Significant evidence for association with prostate cancer risk for both the M9V and D175G variants was observed in the Tasmanian prostate cancer dataset. Whilst this association remained significant, it was diminished when relatedness amongst the familial prostate cancer cases was considered. CONCLUSION. This study, performed in a relatively genetically homogenous Tasmanian population, provides further evidence for a significant association between variants within the AMACR gene and prostate cancer risk. Risk was found to be more significantly associated with AMACR gene variants in sporadic compared to familial prostate cancer cases. These findings again highlight that genetic heterogeneity in the study population should be considered when examining genetic risk factors in prostate cancer.
Publisher: WILEY-LISS
Keywords: COENZYME-A RACEMASE; SUSCEPTIBILITY GENES; LINKAGE ANALYSIS; EXPRESSION; FAMILIES; SCAN; LOCALIZATION; CHROMOSOME-1; HAPLOTYPES; BIOMARKER
Publisher's Version: https://doi.org/10.1002/pros.20798
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Creation Date: 2008-09-15 12:00:00