Sequence variation in alpha-methylacyl-CoA racemase and risk of early-onset and familial prostate cancer.

Published

Journal Article

BACKGROUND: Expression of the alpha-methylacyl-CoA racemase (AMACR) gene has been established as a sensitive and specific biomarker for the diagnosis of prostate cancer. An initial study has also suggested that the risk of familial (but not sporadic) prostate cancer may be associated with germline variation in the AMACR gene. METHODS: In a study of brothers discordant for the diagnosis of prostate cancer (including 449 affected and 394 unaffected men) from 332 familial and early-onset prostate cancer families, we used conditional logistic regression and family-based association tests to investigate the association between prostate cancer and five single nucleotide polymorphisms (SNPs) tagging common haplotype variation within the coding and regulatory regions of AMACR. RESULTS: The strongest evidence for prostate cancer association was for SNP rs3195676, with an estimated odds ratio of 0.58 (95% confidence interval = 0.38-0.90; P = 0.01 for a recessive model). This non-synonymous SNP (nsSNP) results in a methionine-to-valine substitution at codon 9 (M9V) in exon 2 of the AMACR gene. Three additional nsSNPs showed suggestive evidence for prostate cancer association (P < or = 0.10). CONCLUSIONS: Our results confirm an initial report of association between the AMACR gene and the risk of familial prostate cancer. These findings emphasize the value of studying early-onset and familial prostate cancer when attempting to identify genetic variation associated with prostate cancer.

Full Text

Duke Authors

Cited Authors

  • Levin, AM; Zuhlke, KA; Ray, AM; Cooney, KA; Douglas, JA

Published Date

  • October 2007

Published In

Volume / Issue

  • 67 / 14

Start / End Page

  • 1507 - 1513

PubMed ID

  • 17683075

Pubmed Central ID

  • 17683075

Electronic International Standard Serial Number (EISSN)

  • 1097-0045

International Standard Serial Number (ISSN)

  • 0270-4137

Digital Object Identifier (DOI)

  • 10.1002/pros.20642

Language

  • eng