In:
PLOS Medicine, Public Library of Science (PLoS), Vol. 19, No. 1 ( 2022-1-27), p. e1003859-
Abstract:
Numerous epidemiological studies have investigated the role of blood lipids in prostate cancer (PCa) risk, though findings remain inconclusive to date. The ongoing research has mainly involved observational studies, which are often prone to confounding. This study aimed to identify the relationship between genetically predicted blood lipid concentrations and PCa. Methods and findings Data for low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), apolipoprotein A (apoA) and B (apoB), lipoprotein A (Lp(a)), and PCa were acquired from genome-wide association studies in UK Biobank and the PRACTICAL consortium, respectively. We used a two-sample summary-level Mendelian randomisation (MR) approach with both univariable and multivariable (MVMR) models and utilised a variety of robust methods and sensitivity analyses to assess the possibility of MR assumptions violation. No association was observed between genetically predicted concentrations of HDL, TG, apoA and apoB, and PCa risk. Genetically predicted LDL concentration was positively associated with total PCa in the univariable analysis, but adjustment for HDL, TG, and Lp(a) led to a null association. Genetically predicted concentration of Lp(a) was associated with higher total PCa risk in the univariable (OR weighted median per standard deviation (SD) = 1.091; 95% CI 1.028 to 1.157; P = 0.004) and MVMR analyses after adjustment for the other lipid traits (OR IVW per SD = 1.068; 95% CI 1.005 to 1.134; P = 0.034). Genetically predicted Lp(a) was also associated with advanced (MVMR OR IVW per SD = 1.078; 95% CI 0.999 to 1.163; P = 0.055) and early age onset PCa (MVMR OR IVW per SD = 1.150; 95% CI 1.015,1.303; P = 0.028). Although multiple estimation methods were utilised to minimise the effect of pleiotropy, the presence of any unmeasured pleiotropy cannot be excluded and may limit our findings. Conclusions We observed that genetically predicted Lp(a) concentrations were associated with an increased PCa risk. Future studies are required to understand the underlying biological pathways of this finding, as it may inform PCa prevention through Lp(a)-lowering strategies.
Type of Medium:
Online Resource
ISSN:
1549-1676
DOI:
10.1371/journal.pmed.1003859
DOI:
10.1371/journal.pmed.1003859.g001
DOI:
10.1371/journal.pmed.1003859.t001
DOI:
10.1371/journal.pmed.1003859.t002
DOI:
10.1371/journal.pmed.1003859.s001
DOI:
10.1371/journal.pmed.1003859.s002
DOI:
10.1371/journal.pmed.1003859.s003
DOI:
10.1371/journal.pmed.1003859.s004
DOI:
10.1371/journal.pmed.1003859.s005
DOI:
10.1371/journal.pmed.1003859.s006
DOI:
10.1371/journal.pmed.1003859.s007
DOI:
10.1371/journal.pmed.1003859.s008
DOI:
10.1371/journal.pmed.1003859.s009
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10.1371/journal.pmed.1003859.s010
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10.1371/journal.pmed.1003859.s011
DOI:
10.1371/journal.pmed.1003859.s012
DOI:
10.1371/journal.pmed.1003859.s013
DOI:
10.1371/journal.pmed.1003859.s014
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10.1371/journal.pmed.1003859.s015
DOI:
10.1371/journal.pmed.1003859.s016
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10.1371/journal.pmed.1003859.s017
DOI:
10.1371/journal.pmed.1003859.s018
DOI:
10.1371/journal.pmed.1003859.s019
DOI:
10.1371/journal.pmed.1003859.s020
DOI:
10.1371/journal.pmed.1003859.s021
DOI:
10.1371/journal.pmed.1003859.s022
DOI:
10.1371/journal.pmed.1003859.s023
DOI:
10.1371/journal.pmed.1003859.s024
DOI:
10.1371/journal.pmed.1003859.s025
DOI:
10.1371/journal.pmed.1003859.s026
DOI:
10.1371/journal.pmed.1003859.s027
DOI:
10.1371/journal.pmed.1003859.r001
DOI:
10.1371/journal.pmed.1003859.r002
DOI:
10.1371/journal.pmed.1003859.r003
DOI:
10.1371/journal.pmed.1003859.r004
DOI:
10.1371/journal.pmed.1003859.r005
DOI:
10.1371/journal.pmed.1003859.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2164823-2
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