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: 5.09). 10/2008; 123(7):1693-8. DOI: 10.1002/ijc.23715
Source: PubMed


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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Available from: Steven Clinton, Jun 01, 2014
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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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    ABSTRACT: The aberrant blood lipoprotein levels in cancer patients are reported to be associated with cancer risk and mortality incidents however, there are several discrepancies in the previous reports. Hence the clinical usefulness of plasma/serum levels in risk stratification of a variety of cancers remains elusive. The present review highlights and compiles findings from different research groups regarding association of plasma lipoproteins levels with the risk of developing various types of cancer. We will discuss some prospective underlying mechanisms for this reported association. In addition to that the potential roles of plasma lipids in promoting carcinogenesis will be conferred.
    Full-text · Article · Apr 2014 · Biochimie
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    • "Recently several authors reported positive associations between TSC levels and aggressive prostate cancer [11]–[13], even when TSC was not associated with overall prostate cancer [11]. Unfortunately, we did not have information regarding prostate cancer grading in our data, so we cannot contribute to this discussion. "
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    ABSTRACT: Objective To investigate the association between total serum cholesterol (TSC) and cancer incidence in the Metabolic syndrome and Cancer project (Me-Can). Methods Me-Can consists of seven cohorts from Norway, Austria, and Sweden including 289,273 male and 288,057 female participants prospectively followed up for cancer incidence (n = 38,978) with a mean follow-up of 11.7 years. Cox regression models with age as the underlying time metric were used to estimate hazard ratios (HR) and their 95% confidence intervals (CI) for quintiles of cholesterol levels and per 1 mmol/l, adjusting for age at first measurement, body mass index (BMI), and smoking status. Estimates were corrected for regression dilution bias. Furthermore, we performed lag time analyses, excluding different times of follow-up, in order to check for reverse causation. Results In men, compared with the 1st quintile, TSC concentrations in the 5th quintile were borderline significantly associated with decreasing risk of total cancer (HR = 0.94; 95%CI: 0.88, 1.00). Significant inverse associations were observed for cancers of the liver/intrahepatic bile duct (HR = 0.14; 95%CI: 0.07, 0.29), pancreas cancer (HR = 0.52, 95% CI: 0.33, 0.81), non-melanoma of skin (HR = 0.67; 95%CI: 0.46, 0.95), and cancers of the lymph−/hematopoietic tissue (HR = 0.68, 95%CI: 0.54, 0.87). In women, hazard ratios for the 5th quintile were associated with decreasing risk of total cancer (HR = 0.86, 95%CI: 0.79, 0.93) and for cancers of the gallbladder (HR = 0.23, 95%CI: 0.08, 0.62), breast (HR = 0.70, 95%CI: 0.61, 0.81), melanoma of skin (HR = 0.61, 95%CI: 0.42, 0.88), and cancers of the lymph−/hematopoietic tissue (HR = 0.61, 95%CI: 0.44, 0.83). Conclusion TSC was negatively associated with risk of cancer overall in females and risk of cancer at several sites in both males and females. In lag time analyses some associations persisted, suggesting that for these cancer sites reverse causation did not apply.
    Full-text · Article · Jan 2013 · PLoS ONE
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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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    ABSTRACT: Objective: Egg consumption has been suggested to increase the risk of colorectal and some other cancers. The present study summarized and quantified the current evidence relating dietary intake of eggs and prostate cancer. Materials and methods: Literature searches were conducted to identify peer-reviewed manuscripts published up to July 2012. Twenty manuscripts from nine cohort studies and 11 case-control studies were identified. Summary risk estimates with 95% confidence intervals (CIs) were calculated for case-control and cohort studies separately. Results: Neither the case-control not the cohort studies showed any association of prostate cancer incidence with egg consumption (case-control studies: odds ratio 1.09, 95% CI 0.86-1.31; cohort studies: relative risk 0.97, 95% CI 0.97-1.07). The results were consistent in subgroup analysis. Furthermore, no association was observed between egg consumption and prostate cancer-specific mortality. Conclusions: Our analyses provided no evidence of a significant influence of egg consumption on prostate cancer incidence and mortality. However, more studies, particularly large prospective studies, are needed.
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