Association between plasma cholesterol and prostate cancer. Free

A179

Objectives: We previously found that men who used cholesterol-lowering statin drugs experience half the risk of advanced prostate cancer. It was suggested that use of these drugs was inversely associated with the risk of high-grade prostate cancer, but not with organ-confined or low-grade disease. Cholesterol is critical for sex steroid hormone production, sonic hedgehog activity, and cell membrane fluidity and associated receptor signaling, all factors that could influence carcinogenesis. Also, prostate cancer cells exhibit cholesterol dysregulation. Thus, we investigated whether lower plasma cholesterol is associated with a lower risk of prostate cancer overall and by stage and grade. Methods: Participants were drawn from among the 18,018 members of the Health Professionals Follow-up Study who provided a blood specimen between 1993 and 1995. From among these men, we ascertained 698 incident prostate cancer cases diagnosed after blood draw through January 2000. Controls were 698 men who had a PSA test after the date of providing a blood specimen and who were individually matched to cases on age and other factors. Plasma concentration of total cholesterol was measured using the Infinity Total Cholesterol enzymatic assaykit (Sigma Diagnostics, St. Louis, MO). Conditional logistic regression was used to estimate multivariable odds ratios (OR) and 95% confidence intervals (CI) of total prostate cancer, organ-confined (n=515), advanced (T3b or worse; n=62), low-grade (Gleason sum < 7; n=386), and high-grade (Gleason ≥ 7, n=244) disease. Results: Mean plasma cholesterol concentration did not differ between the prostate cancer cases and controls (p=0.80). Comparing < 25^th percentile of plasma cholesterol concentration to ≥ 25^th percentile, the multivariable-adjusted ORs (95% CI) were: total prostate cancer 0.92 (0.71-1.18), organ-confined 0.84 (0.62-1.13), advanced 0.48 (0.16-1.44), low-grade 1.02 (0.72-1.46), and high-grade 0.61 (0.38-0.97). After excluding men who had ever used cholesterol-lowering drugs, the ORs were: total prostate cancer 0.92 (0.71-1.19), organ-confined 0.86 (0.63-1.16), advanced 0.73 (0.28-1.88), low grade 1.01 (0.71-1.46), and high grade 0.67 (0.43-1.05). Conclusion: Men with low plasma cholesterol had a lower risk of high-grade and possibly advanced prostate cancer, but not prostate cancer overall. The results of the present study coupled with our finding for statins, suggest a line of mechanistic studies on cholesterol intake and metabolism that should be pursued for understanding means for preventing prostate cancers having a poorer prognosis.