Teemu J Murtola1,2, Tatu V J Kasurinen3, Kirsi Talala4, Kimmo Taari5, Teuvo L J Tammela3,6, Anssi Auvinen7. 1. Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland. teemu.murtola@uta.fi. 2. Department of Urology, Tampere University Hospital, Tampere, Finland. teemu.murtola@uta.fi. 3. Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland. 4. Finnish Cancer Registry, Helsinki, Finland. 5. Department of Urology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 6. Department of Urology, Tampere University Hospital, Tampere, Finland. 7. Faculty of Social Sciences, University of Tampere, Tampere, Finland.
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.
RCT Entities:
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.
Authors: Emanuela Taioli; William K Oh; Yixuan Gong; Li Wang; Haocheng Yu; Naomi Alpert; Mitchell D Cohen; Colette Prophete; Lori Horton; Maureen Sisco; Sung-Hyun Park; Hyun-Wook Lee; Judith Zelikoff; Lung-Chi Chen; Dana Hashim; Mayte Suarez-Farinas; Michael J Donovan; Stuart A Aaronson; Matthew Galsky; Jun Zhu Journal: Mol Cancer Res Date: 2019-06-20 Impact factor: 5.852