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Initial CDAS Request Approval
Jun 4, 2008
CASP8 and Prostate Cancer
Caspase 8 D302H has been associated with a reduced risk of breast cancer (MacPherson, Healey et al. 2004; Cox, Dunning et al. 2007). MacPherson et al examined two large cohort of breast cancer patients and controls and demonstrated in both populations a significant dose dependent reduction in breast cancer risk (OR 0.83; 95% CI 0.74-0.94 for DH and 0.58; 95% CI 0.39-0.88 for HH). A second confirmatory study demonstrated a similar reduction in breast cancer risk (OR 0.89; 95% confidence CI 0.85-0.94 for DH and 0.74 95% CI; 0.62-0.87 for HH). This variant had not been studied to date in prostate carcinoma. We tested the hypothesis that the H (Histidine) variant was protective for aggressive PCa. A two stage analysis was performed. The primary study evaluated 185 European American (EA) patients/236 EA controls and 73 African Americans (AA)/206 AA controls. The H allele was associated with a reduced risk of aggressive PCa in the EA cohort (Ptrend = 0.03) and but not the AA cohort (Ptrend = 0.12). The second stage analysis of 305 EA patients/305 EA controls and 79 AA patients/158 AA controls confirmed the initial results (EA: Ptrend = 0.04 and AA: Ptrend = 0.42). CGEMS whole genome scan shows several SNPs in this gene region associated with prostate cancer in the PLCO Trial. While the D302H SNP has not been analyzed, we plan to impute the genotype for the PLCO cohort to determine if an association exists with prostate cancer in general and specifically with aggressive disease.
Specific Aim: To determine if CASP* variant D302H is associated with prostate cancer risk in general and specifically if it is associated with risk of aggressive disease.