Abstract
Background
Hypercholesterolemia has been associated with advanced stage prostate cancer (PCa), but the role of lipid parameters such as HDL and triglycerides is unclear. We examined PCa risk by lipid parameters in a population nested within the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC).
Methods
Cholesterol measurements were available on 17,696 men. During the 17-year median follow-up, 2404 PCa cases were diagnosed. Cox regression model was used to estimate hazard ratios (HR) and their 95% confidence intervals (95% CI) for overall PCa risk and stratified by Gleason grade and tumor stage. We compared normolipidemic and hyperlipidemic men on four cholesterol parameters total cholesterol (TC), HDL, LDL, and triglycerides (TG), analyzed as time-dependent variables.
Results
TC in the highest tertile (above 5.1 mmol/l) and LDL above 3 mmol/l were associated with increased risk of Gleason 8–10 cancer (HR 1.42, 95% CI 1.04–1.95 and HR 1.38, 95% CI 1.02–1.86, respectively). Further, overall PCa risk was elevated in the 3-year lag time analysis by TC in the highest two tertiles (HR 1.27, 95% CI 1.05–1.54 for TC above 4.4 mmol/l, and HR 1.26, 95% CI 1.05–1.51 for TC above 5.1 mmol/l) and HDL in the highest tertile (HR 1.33, 95% CI 1.08–1.64) and above 1 mmol/l (HR 1.29, 95% CI 1.01–1.65). In contrast, TC in the highest tertile was associated with a decreased risk of PCa with 20-year lag time. The risk associations for overall PCa grew stronger with added lag time but were observed only in the FinRSPC control arm. Statin use did not modify the risk association.
Conclusions
Hypercholesterolemia may increase overall PCa risk in short-term, inverse risk association was observed with 20-years’ time lag. Similar risk increase of overall PCa was also observed for elevated HDL, conflicting with previous findings on the subject.
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The manuscript was supported by a competitive research grant from the Expert Responsibility Area of The Pirkanmaa Hospital District to TJM. Dr. TJM has worked as a paid consultant for Astellas and Janssen-Cilag and received lecture fees from Astellas, Janssen-Cilag, Abbvie and MSD. Dr. KT has received consulting fees from Abbvie, research funding from Medivation, and travel support from Astellas, and Orion. Professor TLJT has worked as a paid consultant for Astellas and Janssen-Cilag, and received lecture fees from Astellas, Janssen-Cilag, Abbvie and MSD. Professor AA has received a lecture fee from MSD, and worked as a paid consultant for Epid Research Inc. The remaining authors declare that they have no conflict of interest.
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Murtola, T.J., Kasurinen, T.V.J., Talala, K. et al. Serum cholesterol and prostate cancer risk in the Finnish randomized study of screening for prostate cancer. Prostate Cancer Prostatic Dis 22, 66–76 (2019). https://doi.org/10.1038/s41391-018-0087-0
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DOI: https://doi.org/10.1038/s41391-018-0087-0
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