Abstract A102: Men with low serum cholesterol have a lower risk of high-grade prostate cancer in the Prostate Cancer Prevention Trial

Several prospective studies suggest that use of cholesterol-lowering statin drugs is inversely associated with advanced and possibly high-grade prostate cancer. A nested case-control study investigating low circulating cholesterol as a possible mechanism underlying these findings reported that men with a lower cholesterol concentration had a lower risk of high-grade and possibly advanced prostate cancer (Int J Cancer 2008;123:1693-8). Given these findings, we investigated the association of low serum cholesterol with prostate cancer overall and by histologic grade in the Prostate Cancer Prevention Trial (PCPT). Unlike standard cohort studies, men in the PCPT underwent PSA screening annually, cases were biopsy detected, diagnoses and Gleason sum determinations were confirmed centrally, and controls were men who were biopsied at the end of the trial per trial protocol irrespective of indication.

We conducted a prospective cohort study of 5,616 men aged 55+ years old randomized to the placebo arm of the PCPT between 1993 and 1996 and who had serum cholesterol measured at entry. By the end of follow-up, 1,251 cases were confirmed. Serum cholesterol concentration was measured enzymatically. We used logistic regression to calculate the multivariable odds ratio (OR) of total, organ-confined, and Gleason sum ≥ 8 (n=59), 7 (n=199), and < 7 (n=993) prostate cancer comparing low (normal: < 200 mg/dL) to high (borderline and elevated cholesterol: ≥ 200 mg/dL) serum cholesterol.

Men with low cholesterol had a lower risk of Gleason sum ≥ 8 prostate cancer (OR=0.41, 95% confidence interval (CI) 0.22-0.77; p-trend across quintiles of cholesterol = 0.01) compared with men with high cholesterol; this association was stronger after restricting to organ-confined disease (OR=0.32, 95% CI 0.15-0.66, p-trend < 0.001). No association was present for prostate cancer overall (OR=0.97, 95% CI 0.85-1.11, p-trend=0.43), or Gleason < 7 (OR=1.03, 95% CI 0.89-1.18, p-trend=0.94) or 7 (OR=0.93, 95% CI 0.69-1.24, p-trend=0.49) disease.

These prospective findings from the PCPT, in which the opportunity for detection of high-grade prostate cancer was similar because all men underwent biopsy, suggest that low cholesterol may protect against the development of high-grade prostate cancer. The contemporary body of literature on statins, cholesterol, and prostate cancer suggests that cholesterol metabolism should be investigated further in the etiology of prostate cancer that has a worse prognosis.

Funding: NCI/NIH P01 CA108964 (Biology of the PCPT). The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):A102.