Lipids, cholesterols, statins and liver cancer: a Mendelian randomization study
AimTo investigate the causal relationship of serum lipid indicators and lipid-lowering drugs with the risk of liver cancer using Mendelian randomization study.MethodsA two-sample Mendelian randomization (TSMR) study was performed to investigate the causal relationship between serum levels of lipid i...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-09-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1251873/full |
| _version_ | 1797691110926057472 |
|---|---|
| author | Zicheng Liang Zhen Zhang Xiaoning Tan Puhua Zeng |
| author_facet | Zicheng Liang Zhen Zhang Xiaoning Tan Puhua Zeng |
| author_sort | Zicheng Liang |
| collection | DOAJ |
| description | AimTo investigate the causal relationship of serum lipid indicators and lipid-lowering drugs with the risk of liver cancer using Mendelian randomization study.MethodsA two-sample Mendelian randomization (TSMR) study was performed to investigate the causal relationship between serum levels of lipid indicators and liver cancer, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), total cholesterol (TC), Apolipoprotein B (ApoB), and Apolipoprotein A1 (ApoA1).Furthermore, instrumental variable weighted regression (IVW) and summary data-based MR (SMR) analyses were performed to investigate the causal effects of lipid-lowering drugs, including statins and PCSK9 inhibitors, on the risk of liver cancer.ResultsSerum LDL-c and serum TC levels showed negatively associated with liver cancer (n = 22 SNPs, OR = 0.363, 95% CI = 0.231 - 0.570; p = 1.070E-5) (n = 83 SNPs; OR = 0.627, 95% CI = 0.413-0.952; p = 0.028). However, serum levels of TG, HDL-c, and ApoA1 did not show any significant correlation with liver cancer. In the drug target MR (DMR) analyses, HMGCR–mediated level of LDL-c showed an inverse relationship with the risk of liver cancer in the IVW-MR analysis (n = 5 SNPs, OR = 0.201, 95% CI = 0.064 - 0.631; p = 5.95E-03) and SMR analysis (n = 20 SNPs, OR = 0.245, 95% CI = 0.065 - 0.926; p = 0.038) However, PCSK9 did not show any significant association with liver cancer based on both the IVW-MR and SMR analyses.ConclusionOur results demonstrated that reduced levels of LDL-c and TC were associated with an increased risk of liver cancer. Furthermore, lipid-lowering drugs targeting HMGCR such as statins were associated with increased risk of liver cancer. |
| first_indexed | 2024-03-12T02:09:40Z |
| format | Article |
| id | doaj.art-eb997939b27f4f7c86f4d3b6149024b0 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-12T02:09:40Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-eb997939b27f4f7c86f4d3b6149024b02023-09-06T17:11:49ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-09-011310.3389/fonc.2023.12518731251873Lipids, cholesterols, statins and liver cancer: a Mendelian randomization studyZicheng Liang0Zhen Zhang1Xiaoning Tan2Puhua Zeng3Graduate School, Hunan University of Traditional Chinese Medicine, Changsha, ChinaDepartment of Oncology, Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, ChinaDepartment of Oncology, Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, ChinaDepartment of Oncology, Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, ChinaAimTo investigate the causal relationship of serum lipid indicators and lipid-lowering drugs with the risk of liver cancer using Mendelian randomization study.MethodsA two-sample Mendelian randomization (TSMR) study was performed to investigate the causal relationship between serum levels of lipid indicators and liver cancer, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), total cholesterol (TC), Apolipoprotein B (ApoB), and Apolipoprotein A1 (ApoA1).Furthermore, instrumental variable weighted regression (IVW) and summary data-based MR (SMR) analyses were performed to investigate the causal effects of lipid-lowering drugs, including statins and PCSK9 inhibitors, on the risk of liver cancer.ResultsSerum LDL-c and serum TC levels showed negatively associated with liver cancer (n = 22 SNPs, OR = 0.363, 95% CI = 0.231 - 0.570; p = 1.070E-5) (n = 83 SNPs; OR = 0.627, 95% CI = 0.413-0.952; p = 0.028). However, serum levels of TG, HDL-c, and ApoA1 did not show any significant correlation with liver cancer. In the drug target MR (DMR) analyses, HMGCR–mediated level of LDL-c showed an inverse relationship with the risk of liver cancer in the IVW-MR analysis (n = 5 SNPs, OR = 0.201, 95% CI = 0.064 - 0.631; p = 5.95E-03) and SMR analysis (n = 20 SNPs, OR = 0.245, 95% CI = 0.065 - 0.926; p = 0.038) However, PCSK9 did not show any significant association with liver cancer based on both the IVW-MR and SMR analyses.ConclusionOur results demonstrated that reduced levels of LDL-c and TC were associated with an increased risk of liver cancer. Furthermore, lipid-lowering drugs targeting HMGCR such as statins were associated with increased risk of liver cancer.https://www.frontiersin.org/articles/10.3389/fonc.2023.1251873/fullMendelian randomizationlipidscholesterolsstatinsliver cancer |
| spellingShingle | Zicheng Liang Zhen Zhang Xiaoning Tan Puhua Zeng Lipids, cholesterols, statins and liver cancer: a Mendelian randomization study Frontiers in Oncology Mendelian randomization lipids cholesterols statins liver cancer |
| title | Lipids, cholesterols, statins and liver cancer: a Mendelian randomization study |
| title_full | Lipids, cholesterols, statins and liver cancer: a Mendelian randomization study |
| title_fullStr | Lipids, cholesterols, statins and liver cancer: a Mendelian randomization study |
| title_full_unstemmed | Lipids, cholesterols, statins and liver cancer: a Mendelian randomization study |
| title_short | Lipids, cholesterols, statins and liver cancer: a Mendelian randomization study |
| title_sort | lipids cholesterols statins and liver cancer a mendelian randomization study |
| topic | Mendelian randomization lipids cholesterols statins liver cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1251873/full |
| work_keys_str_mv | AT zichengliang lipidscholesterolsstatinsandlivercanceramendelianrandomizationstudy AT zhenzhang lipidscholesterolsstatinsandlivercanceramendelianrandomizationstudy AT xiaoningtan lipidscholesterolsstatinsandlivercanceramendelianrandomizationstudy AT puhuazeng lipidscholesterolsstatinsandlivercanceramendelianrandomizationstudy |