Sequence variation in alpha-methylacyl-CoA racemase and risk of early-onset and familial prostate cancer.
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.
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109-0618, USA.
Albert M
AM
Levin
Kimberly A
KA
Zuhlke
Anna M
AM
Ray
Kathleen A
KA
Cooney
Julie A
JA
Douglas
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000556:secondary; D015415:Biomarkers / Q000097:blood; D005192:Family Health; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D019998:Racemases and Epimerases / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D035781:Siblings
D015415:Biomarkers; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase