The impact of lipidome on breast cancer: a Mendelian randomization study
Abstract Objective This study aims to investigate the association between specific lipidomes and the risk of breast cancer (BC) using the Two-Sample Mendelian Randomization (TSMR) approach and Bayesian Model Averaging Mendelian Randomization (BMA-MR) method. Method The study analyzed data from large...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12944-024-02103-2 |
| _version_ | 1797199166401675264 |
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| author | Yuchen Cao Meichen Ai Chunjun Liu |
| author_facet | Yuchen Cao Meichen Ai Chunjun Liu |
| author_sort | Yuchen Cao |
| collection | DOAJ |
| description | Abstract Objective This study aims to investigate the association between specific lipidomes and the risk of breast cancer (BC) using the Two-Sample Mendelian Randomization (TSMR) approach and Bayesian Model Averaging Mendelian Randomization (BMA-MR) method. Method The study analyzed data from large-scale GWAS datasets of 179 lipidomes to assess the relationship between lipidomes and BC risk across different molecular subtypes. TSMR was employed to explore causal relationships, while the BMA-MR method was carried out to validate the results. The study assessed heterogeneity and horizontal pleiotropy through Cochran's Q, MR-Egger intercept tests, and MR-PRESSO. Moreover, a leave-one-out sensitivity analysis was performed to evaluate the impact of individual single nucleotide polymorphisms on the MR study. Results By examining 179 lipidome traits as exposures and BC as the outcome, the study revealed significant causal effects of glycerophospholipids, sphingolipids, and glycerolipids on BC risk. Specifically, for estrogen receptor-positive BC (ER+ BC), phosphatidylcholine (P < 0.05) and phosphatidylinositol (OR: 0.916–0.966, P < 0.05) within glycerophospholipids play significant roles, along with the importance of glycerolipids (diacylglycerol (OR = 0.923, P < 0.001) and triacylglycerol, OR: 0.894–0.960, P < 0.05)). However, the study did not observe a noteworthy impact of sphingolipids on ER+BC. In the case of estrogen receptor-negative BC (ER− BC), not only glycerophospholipids, sphingolipids (OR = 1.085, P = 0.008), and glycerolipids (OR = 0.909, P = 0.002) exerted an influence, but the protective effect of sterols (OR: 1.034–1.056, P < 0.05) was also discovered. The prominence of glycerolipids was minimal in ER-BC. Phosphatidylethanolamine (OR: 1.091–1.119, P < 0.05) was an important causal effect in ER−BC. Conclusions The findings reveal that phosphatidylinositol and triglycerides levels decreased the risk of BC, indicating a potential protective role of these lipid molecules. Moreover, the study elucidates BC's intricate lipid metabolic pathways, highlighting diverse lipidome structural variations that may have varying effects in different molecular subtypes. |
| first_indexed | 2024-04-24T07:11:26Z |
| format | Article |
| id | doaj.art-04cdc7418d7f4907ac9a09baf39283d6 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-04-24T07:11:26Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-04cdc7418d7f4907ac9a09baf39283d62024-04-21T11:28:48ZengBMCLipids in Health and Disease1476-511X2024-04-0123111110.1186/s12944-024-02103-2The impact of lipidome on breast cancer: a Mendelian randomization studyYuchen Cao0Meichen Ai1Chunjun Liu2Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeSouthern Medical UniversityPlastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Objective This study aims to investigate the association between specific lipidomes and the risk of breast cancer (BC) using the Two-Sample Mendelian Randomization (TSMR) approach and Bayesian Model Averaging Mendelian Randomization (BMA-MR) method. Method The study analyzed data from large-scale GWAS datasets of 179 lipidomes to assess the relationship between lipidomes and BC risk across different molecular subtypes. TSMR was employed to explore causal relationships, while the BMA-MR method was carried out to validate the results. The study assessed heterogeneity and horizontal pleiotropy through Cochran's Q, MR-Egger intercept tests, and MR-PRESSO. Moreover, a leave-one-out sensitivity analysis was performed to evaluate the impact of individual single nucleotide polymorphisms on the MR study. Results By examining 179 lipidome traits as exposures and BC as the outcome, the study revealed significant causal effects of glycerophospholipids, sphingolipids, and glycerolipids on BC risk. Specifically, for estrogen receptor-positive BC (ER+ BC), phosphatidylcholine (P < 0.05) and phosphatidylinositol (OR: 0.916–0.966, P < 0.05) within glycerophospholipids play significant roles, along with the importance of glycerolipids (diacylglycerol (OR = 0.923, P < 0.001) and triacylglycerol, OR: 0.894–0.960, P < 0.05)). However, the study did not observe a noteworthy impact of sphingolipids on ER+BC. In the case of estrogen receptor-negative BC (ER− BC), not only glycerophospholipids, sphingolipids (OR = 1.085, P = 0.008), and glycerolipids (OR = 0.909, P = 0.002) exerted an influence, but the protective effect of sterols (OR: 1.034–1.056, P < 0.05) was also discovered. The prominence of glycerolipids was minimal in ER-BC. Phosphatidylethanolamine (OR: 1.091–1.119, P < 0.05) was an important causal effect in ER−BC. Conclusions The findings reveal that phosphatidylinositol and triglycerides levels decreased the risk of BC, indicating a potential protective role of these lipid molecules. Moreover, the study elucidates BC's intricate lipid metabolic pathways, highlighting diverse lipidome structural variations that may have varying effects in different molecular subtypes.https://doi.org/10.1186/s12944-024-02103-2LipidomeBreast cancerMendelian randomizationBayesian model averaging mendelian randomizationEstrogen receptor |
| spellingShingle | Yuchen Cao Meichen Ai Chunjun Liu The impact of lipidome on breast cancer: a Mendelian randomization study Lipids in Health and Disease Lipidome Breast cancer Mendelian randomization Bayesian model averaging mendelian randomization Estrogen receptor |
| title | The impact of lipidome on breast cancer: a Mendelian randomization study |
| title_full | The impact of lipidome on breast cancer: a Mendelian randomization study |
| title_fullStr | The impact of lipidome on breast cancer: a Mendelian randomization study |
| title_full_unstemmed | The impact of lipidome on breast cancer: a Mendelian randomization study |
| title_short | The impact of lipidome on breast cancer: a Mendelian randomization study |
| title_sort | impact of lipidome on breast cancer a mendelian randomization study |
| topic | Lipidome Breast cancer Mendelian randomization Bayesian model averaging mendelian randomization Estrogen receptor |
| url | https://doi.org/10.1186/s12944-024-02103-2 |
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