Association of a CAV-1 haplotype to familial aggressive prostate cancer.
BACKGROUND
Multiple lines of evidence have implicated the CAV-1 gene in prostate cancer progression. CAV-1 is located within the prostate cancer aggressiveness locus at 7q31-33, and was identified as being overexpressed in prostate tumors. Mutation screening was performed as well as a case-control study to examine if polymorphisms in CAV-1 are associated with prostate cancer aggressiveness in a German population.


METHODS
We sequenced the CAV-1 promoter region and its open reading frame in prostate cancer families with linkage to chromosome 7q31-33. Additionally, 105 unrelated familial prostate cancer probands, 190 sporadic cases, and 191 controls were genotyped at four intronic single nucleotide polymorphisms. Resulting haplotypes were tested for association using age at diagnosis, tumor grade, TNM stage, and follow up information to stratify for aggressive disease.


RESULTS
No mutation was found in the CAV-1 coding region or in the promoter. One of the 11 observed haplotypes showed an increased frequency in cases with high tumor stage (P = 0.03).


CONCLUSIONS
This is the first report providing evidence for CAV-1 being involved in predisposition to aggressive prostate cancer. The association of a potential risk haplotype agrees well with a role of CAV-1 in tumor progression but needs further confirmation.
Haeusler
Juergen
J
Department of Human Genetics, University of Ulm, Germany.
Hoegel
Josef
J
Bachmann
Natascha
N
Herkommer
Kathleen
K
Paiss
Thomas
T
Vogel
Walther
W
Maier
Christiane
C
D000328:Adult; D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics* / Q000502:physiology*; D004252:DNA Mutational Analysis; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
D051242:Caveolin 1; D022461:Caveolins