Association of caveolin-1 and -2 genetic variants and post-treatment serum caveolin-1 with prostate cancer risk and outcomes.
BACKGROUND
Caveolin-1 (cav-1) is overexpressed by metastatic prostate cancer (PC) cells. Pre-operative serum cav-1 levels have been shown to be a prognostic marker for PC recurrence. This study evaluated the relationship between post-treatment serum cav-1 levels and single nucleotide polymorphisms (SNPs) in the cav-1 and -2 genes with risk of PC, aggressive PC, PC recurrence or death.


METHODS
Two case-control studies of PC among men in Washington State were combined for this analysis. Cases (n = 1,458) were diagnosed in 1993-1996 or 2002-2005 and identified via a SEER cancer registry. Age-matched controls (n = 1,351) were identified via random digit dialing. Logistic regression was used to assess the relationship between exposures (19 haplotype-tagging SNPs from all subjects and post-treatment serum cav-1 levels from a sample of 202 cases and 226 controls) and PC risk and aggressive PC. Cox proportional hazards regression was used to assess the relationship between exposures and PC recurrence and death.


RESULTS
Rs9920 in cav-1 was associated with an increased relative risk of overall PC (OR(CT + CC) = 1.37, 95% CI = 1.12, 1.68) and aggressive PC (OR(CT + CC) = 1.57, 95% CI = 1.20, 2.06), but not with PC recurrence or death. High post-treatment serum cav-1 levels were not associated with PC risk, aggressive PC, or PC-specific death, but approached a significant inverse association with PC recurrence (hazard ratio = 0.69, 95% CI = 0.47, 1.00).


CONCLUSIONS
We found modest evidence for an association with a variant in the cav-1 gene and risk of overall PC and aggressive PC, which merits further study. We found no evidence that higher post-treatment serum cav-1 is associated with risk of aggressive PC or adverse PC outcomes.
Langeberg
Wendy J
WJ
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Tahir
Salahaldin A
SA
Feng
Ziding
Z
Kwon
Erika M
EM
Ostrander
Elaine A
EA
Thompson
Timothy C
TC
Stanford
Janet L
JL
D000328:Adult; D000368:Aged; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000097:blood* / Q000235:genetics*; D051243:Caveolin 2 / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000628:therapy; D012044:Regression Analysis; D018570:Risk Assessment; D018426:SEER Program; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D051242:Caveolin 1; D051243:Caveolin 2