Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study

Abstract

BackgroundEpidemiologic evidence for a serum cholesterol-prostate cancer link is mixed. Prostate-specific antigen (PSA) is positively correlated with cholesterol, potentially increasing PSA-driven biopsy recommendations in men with high cholesterol, though biopsy compliance may be lower in men with comorbid conditions. These potential biases may affect PSA-driven biopsy rates and subsequent prostate cancer detection in men with high serum cholesterol. Our objective was to test the association between serum cholesterol and prostate cancer risk in men receiving PSA-independent, study-mandated prostate biopsies.MethodsWe conducted a post-hoc analysis of data from 4,974 non-statin users in REDUCE, a randomized trial in men with elevated PSA and a negative baseline biopsy. Men underwent 2- and 4-year trial-mandated prostate biopsies. Associations between baseline serum levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and prostate cancer risk, overall and by Gleason grade (<7 vs. ≥7), were examined using multivariable logistic regression.ResultsHigh total serum cholesterol was associated with an increased risk of high-grade prostate cancer diagnosis (ORper10mg/dl 1.05; 95% CI 1.00-1.09; p=0.048), but cholesterol was unrelated to either overall or low-grade prostate cancer risk (p-values>0.185). There was no association between serum LDL and overall, low- or high-grade prostate cancer risk (p-values>0.137). In contrast, elevated serum HDL was associated with increased risk of both overall (ORper10mg/dl 1.08; 95% CI 1.01-1.16; p=0.033) and high-grade prostate cancer (ORper10mg/dl 1.14; 95% CI 1.01-1.28; p=0.034).ConclusionsIn REDUCE, where all men received PSA-independent, trial-mandated biopsies thus ensuring complete prostate cancer ascertainment, high total serum cholesterol and high HDL were associated with increased risk of high-grade prostate cancer, supporting a cholesterol-prostate cancer link.

Response to response to Jeontausta et al.

“…As pointed out by Dr Kawada, our previous studies have linked elevated serum high‐density lipoprotein (HDL) with worse PCa outcomes. Concordantly, previous studies have also linked elevated HDL with increased risk of advanced PCa and high‐grade PCa . Therefore, despite HDL being a protective factor against atherosclerosis and cardiovascular disease, in PCa its role appears to be quite different.…”

“…Concordantly, previous studies have also linked elevated HDL with increased risk of advanced PCa 2 and high-grade PCa. 3 Therefore, despite HDL being a protective factor against atherosclerosis and cardiovascular disease, in PCa its role appears to be quite different. In PCa the amount of cholesterol available to cancer cells from the serum may be more important than the distribution of cholesterol subtypes.…”

Serum lipids might improve prostate-specific antigen sensitivity in patients undergoing transrectal ultrasonography-guided biopsy for suspected prostate cancer: A pilot study

“…Likewise, hypertriglyceridaemia showed a weak positive but non-significant association with prostate cancer. On the other hand, HDL has been shown also to significantly correlate with high-grade prostate cancer at diagnosis, as shown in the post hoc analysis of the REduction by DUtasteride of prostate Cancer Events (REDUCE) study [15]. Besides a potential role in prostate cancer diagnosis, a serum lipogram has been shown to have prognostic value post-RP.…”

SR-B1 uptake of HDL promotes prostate cancer proliferation and tumor progression

“…However, prostate cancer often becomes resistant to such treatments (29). The effects of HDL on prostate cancer development and progression are controversial, with both positive and inverse associations found in various studies (2)(3)(4)(5). A meta-analysis of 14 large prospective studies found no significant effect of HDLcholesterol on the risk of prostate cancer (30).…”

“…Prostate cancer is the most common malignancy and second leading cause of cancer-related deaths among men in the United States (1). The association of HDL levels with prostate cancer risk has been inconsistent, with some studies showing a positive association (2,3) some showing an inverse association (4,5), and others showing no association (6,7). HDL biogenesis is mediated by ATP-binding cassette transporter A1 (ABCA1), which assembles cellular lipids with exogenous lipid-poor apolipoprotein A1 (apoA1) to generate nascent HDL (8).…”