Background: Previous studies found that low total cholesterol level was associated with a lower risk of high-grade prostate cancer. Apolipoprotein E (ApoE) isoform is associated with total cholesterol level. The aim of this study was to explore associations of ApoE isoforms with prostate cancer risk. Methods: We assessed ApoE genotypes and risk of prostate cancer in a prospective case-control study nested among men who provided a blood sample in 1993-95 within the Health Professionals Follow-up Study. We identified 1,169 incident cases of prostate cancer and 1,233 controls in follow-up through 2004. Associations of ApoE isoform and prostate cancer incidence were evaluated by logistic regression models. Results: We found no statistically significant associations of ApoE variants with overall prostate cancer or Gleason sum ≤ 7 (3+4), Gleason sum ≥ 7 (4+3), clinically localized stage, or progression to metastasis or death. There was no evidence of effect modification by circulating total cholesterol or use of cholesterol lowering drugs prior to diagnosis. Conclusions: ApoE variants were not associated with the risk of prostate cancer or aggressive disease. Impact: Our findings suggest that the mechanism of circulating cholesterol level affecting prostate cancer incidence may not rely on ApoE isoforms.
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