The relationship between lipoprotein A and other lipids with prostate cancer risk: A multivariable Mendelian randomisation study
<strong>Background</strong> 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 s...
| Main Authors: | , , , , , , , , |
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| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2022
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| _version_ | 1826317652047429632 |
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| author | Ioannidou, A Watts, EL Perez-Cornago, A Platz, EA Mills, IG Key, TJ Travis, RC Tsilidis, KK Zuber, V |
| author2 | PRACTICAL consortium |
| author_facet | PRACTICAL consortium Ioannidou, A Watts, EL Perez-Cornago, A Platz, EA Mills, IG Key, TJ Travis, RC Tsilidis, KK Zuber, V |
| author_sort | Ioannidou, A |
| collection | OXFORD |
| description | <strong>Background</strong>
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.
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<strong>Methods and findings</strong>
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 (ORweighted 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 (ORIVW per SD = 1.068; 95% CI 1.005 to 1.134; P = 0.034). Genetically predicted Lp(a) was also associated with advanced (MVMR ORIVW per SD = 1.078; 95% CI 0.999 to 1.163; P = 0.055) and early age onset PCa (MVMR ORIVW 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.
<br>
<strong>Conclusions</strong>
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. |
| first_indexed | 2024-03-07T03:49:40Z |
| format | Journal article |
| id | oxford-uuid:c0c8175f-f072-4eb0-b983-e9adca6e6cf0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-03-11T16:57:18Z |
| publishDate | 2022 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:c0c8175f-f072-4eb0-b983-e9adca6e6cf02025-02-26T09:26:30ZThe relationship between lipoprotein A and other lipids with prostate cancer risk: A multivariable Mendelian randomisation studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c0c8175f-f072-4eb0-b983-e9adca6e6cf0EnglishSymplectic ElementsPublic Library of Science2022Ioannidou, AWatts, ELPerez-Cornago, APlatz, EAMills, IGKey, TJTravis, RCTsilidis, KKZuber, VPRACTICAL consortiumCRUKBPC3CAPSPEGASUS<strong>Background</strong> 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. <br> <strong>Methods and findings</strong> 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 (ORweighted 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 (ORIVW per SD = 1.068; 95% CI 1.005 to 1.134; P = 0.034). Genetically predicted Lp(a) was also associated with advanced (MVMR ORIVW per SD = 1.078; 95% CI 0.999 to 1.163; P = 0.055) and early age onset PCa (MVMR ORIVW 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. <br> <strong>Conclusions</strong> 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. |
| spellingShingle | Ioannidou, A Watts, EL Perez-Cornago, A Platz, EA Mills, IG Key, TJ Travis, RC Tsilidis, KK Zuber, V The relationship between lipoprotein A and other lipids with prostate cancer risk: A multivariable Mendelian randomisation study |
| title | The relationship between lipoprotein A and other lipids with prostate cancer risk: A multivariable Mendelian randomisation study |
| title_full | The relationship between lipoprotein A and other lipids with prostate cancer risk: A multivariable Mendelian randomisation study |
| title_fullStr | The relationship between lipoprotein A and other lipids with prostate cancer risk: A multivariable Mendelian randomisation study |
| title_full_unstemmed | The relationship between lipoprotein A and other lipids with prostate cancer risk: A multivariable Mendelian randomisation study |
| title_short | The relationship between lipoprotein A and other lipids with prostate cancer risk: A multivariable Mendelian randomisation study |
| title_sort | relationship between lipoprotein a and other lipids with prostate cancer risk a multivariable mendelian randomisation study |
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