Article

Association between plasma cholesterol and prostate cancer in the PSA era

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. <>
International Journal of Cancer (Impact Factor: 5.01). 10/2008; 123(7):1693-8. DOI: 10.1002/ijc.23715
Source: PubMed

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.

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    • "It was reported that men with low plasma cholesterol had a lower-risk of high-grade prostate cancer and possibly advanced stage disease, but not organ-confined or low-grade disease [76]. Exclusion of the statin-users did not alter these results e indicating a direct role of cholesterol in mediating this inverse association between statin intake and advanced stage prostate cancer [76]. Another recent work e where statin users were excluded from the study population e suggests that men with low cholesterol have a reduced risk of high-grade prostate cancer [77]. "
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    • "Malignant prostate cells have higher choline concentrations than do healthy cells, and choline kinase is overexpressed in prostate cancer (Glunde et al., 2006; Ramirez de Molina et al., 2008). Blood concentrations of cholesterol and choline have been positively associated with risk of advanced prostate cancer (Platz et al., 2008; Johansson et al., 2009). However, in our study, eggs consumption was associated with a lower incidence of advanced prostate cancer, and no association was observed with fatal prostate cancer, while these results need to be interpreted with caution because of the few studies available. "
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    • "A further epidemiological study also showed that low cholesterol was inversely associated with advanced disease (OR ¼ 0.42, 95% CI ¼ 0.13–1.36). The numbers in this study were small but the senior author (Platz et al, 2008) and others (Solomon and Freeman, 2008) have gone on to propose that statins affect CaP's intracellular cholesterol metabolism, which is known to be dysregulated. The uptake of statins by the liver and the requirement for liver-specific esterases, for example, in the case of the pro-drug simvastatin, limits statin availability in the peripheral circulation (Merck, 2005 "
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