Association between plasma cholesterol and prostate cancer in the PSA era

Abstract

We previously found that statin users had a lower risk of advanced and possibly high-grade prostate cancer compared with nonusers. We hypothesize that statins' effects on cholesterol synthesis may explain those findings because prostate cancer cells exhibit cholesterol dysregulation. Thus, we investigated whether low plasma cholesterol is associated with prostate cancer overall and by stage and grade. Participants were drawn from the 18,018 members of the Health Professionals Follow-Up Study who provided blood in 1993-1995. We ascertained 698 incident cases through January 2000. Controls were 698 men who had a PSA test and were matched to cases. Plasma cholesterol was measured enzymatically. Conditional logistic regression was used to estimate multivariable ORs and 95% CIs of total, clinically organ-confined (n = 518), advanced (T3b or worse; n = 61), low-grade (Gleason sum < 7; n = 386) and high-grade (Gleason sum > or = 7, n = 247) disease. Low cholesterol (<25th percentile vs. > or =25th percentile) was not associated with total (OR = 0.93, 95% CI: 0.72-1.20), organ-confined (OR = 0.87, 95% CI: 0.64-1.18) or low-grade (OR = 1.06, 95% CI: 0.75-1.51) disease. However, men with low cholesterol had a lower risk of high-grade disease (OR = 0.61, 95% CI: 0.39-0.98), especially if organ-confined (OR = 0.54, 95% CI: 0.29-0.99). The association for advanced disease appeared inverse, but number of cases was small (OR = 0.42, 95% CI: 0.13-1.36). Associations remained after excluding cholesterol-lowering drug users. These results coupled with prior statin findings suggest that mechanistic studies on cholesterol metabolism should be pursued to understand a possible target for preventing poorly differentiated prostate cancers.

FIGURE 1

Association of low plasma cholesterol with high and low-grade prostate cancer restricted to men with organ-confined disease. Low plasma cholesterol was defined as below the 25^th percentile of the distribution of plasma cholesterol concentration among controls. The analysis included: 167 high-grade organ-confined case-control pairs (excluding ever use of cholesterol-lowering drugs 152 cases, 153 controls) and 333 low-grade organ-confined case-control pairs (excluding ever use of cholesterol-lowering drugs 304 cases, 292 controls). The ORs of high-grade organ-confined disease and low-grade organ-confined disease were estimated from a conditional logistic regression model and adjusted for family history of prostate cancer, height, vigorous physical activity, diabetes mellitus, vasectomy, cigarette smoking in the past 10 years, intake of energy, red meat, fish, and alcohol, intake of energy-adjusted lycopene, calcium, fructose, and α-linolenic acid, and supplemental vitamin E and selenium. The ORs of these endpoints after excluding ever users of cholesterol-lowering drugs were estimated from a logistic regression model and adjusted for age, PSA test before blood draw, and the other covariates listed for the conditional logistic regression model.