Blood Lipid Metabolic Profiles and Causal Links to Site-Specific Cancer Risks: A Mendelian Randomization Study

Chen, Kai; Li, Jin; Ouyang, Yanfeng; Liu, Guichao; Xie, Yulong; Xu, Guiqiong; Peng, Weibin; Liu, Yonglin; He, Han; Huang, Rong

doi:10.1080/01635581.2023.2294521

Cited by 6 publications

(3 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This seemingly novel perspective is supported by existing evidence as well. Similarly, other Mendelian randomization studies focusing on lipid metabolism and tumor risk also indicate triglycerides as a protective factor for BC, particularly ER + BC [ 49 – 54 ], aligning with our research results. However, as with most complex diseases, common variants identified in GWAS can only explain a small portion of the total heritability of the disease, especially in the case of cancer.…”

Section: Discussionsupporting

confidence: 92%

The impact of lipidome on breast cancer: a Mendelian randomization study

Cao,

Ai,

Liu

2024

Lipids Health Dis

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

The impact of lipidome on breast cancer: a Mendelian randomization study

Cao,

Ai,

Liu

2024

Lipids Health Dis

View full text Add to dashboard Cite

show abstract

“…To ensure the validity of MR analysis, three key assumptions regarding instrumental variables (IVs) must be satisfied: (a) genetic variations must strongly associate with the exposure; (b) genetic variations should remain independent of both measured and unmeasured confounding factors in the exposure–outcome relationship; and (c) genetic variants must remain independent of the outcome given the exposure and confounders. 13 The study flowchart is illustrated in Fig. 1 , and GWAS summary datasets for both exposures and outcomes are provided in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

“…Directional and horizontal pleiotropy tests were conducted using the MR-Egger regression-derived intercept method and MR pleiotropy residual sum and outlier (MR-PRESSO) method, respectively. 13 Additionally, leave-one-out analyses were performed to evaluate the robustness of the MR analysis results by iteratively removing the SNPs one by one.…”

Section: Methodsmentioning

confidence: 99%

Does androgenic alopecia aggravate the risk of prostate cancer? Evidence from Mendelian randomization

Shi,

Pan,

Liu

et al. 2024

Prostate International

Self Cite

View full text Add to dashboard Cite

Associations Between Lipid Traits and Breast Cancer Risk: A Mendelian Randomization Study in African Women

Ansah,

Kyei,

Opoku

et al. 2024

Preprint

View full text Add to dashboard Cite

Blood lipids are associated with breast cancer. An increasing number of reports have attempted to explore the genetic connection between blood lipids and the risk of developing breast cancer. However, observational studies can be affected by confounding factors and reverse causation, which can compromise the reliability of the findings. We used univariate and multivariable two-sample mendelian randomization to explore the causal association between blood lipids and breast cancer. Summary-level data for lipid traits were obtained from the Africa Wits-INDEPTH partnership for Genomic Research (AWI-Gen) (N= 10,603, 58.5% of women). For breast cancer, we leveraged summary statistics from the most comprehensive Genome-wide Association Studies (GWAS) on breast cancer consisting of 18,034 cases and 22,104 controls of women of African ancestry. Our analysis suggests that genetically predicted triglycerides had a potential protective effect on breast carcinoma (OR = 0.73, 95% CI = 0.56, 0.95, FDR = 0.001). We found no evidence that genetically elevated levels of TC, HDL, and LDL may be associated with the risk of breast cancer TC (OR = 1.04; 95% CI, 0.93, 1.18; FDR = 0.029); HDL (OR = 1.29, 95% CI = 0.93, 1.79, FDR = 0.008); LDL (OR = 1.04, 95% CI = 0.90, 1.20, FDR = 0.036). Multivariate mendelian randomization analysis, which adjusted for the effects of TG, TC, LDL, and HDL, attenuated the observation of TG and breast cancer and also found no relationship between TC, HDL, LDL, and breast cancers. Furthermore, there was no evidence for a causal association between lipid traits and breast cancer subtypes. Our findings were robust in several sensitivity analyses. This study provides strong evidence that circulating TG may be associated with a decreased risk of breast cancer, while TC, LDL and HDL may not be related to the risk of breast cancer among African women.

show abstract

Blood Lipid Metabolic Profiles and Causal Links to Site-Specific Cancer Risks: A Mendelian Randomization Study

Cited by 6 publications

References 43 publications

The impact of lipidome on breast cancer: a Mendelian randomization study

The impact of lipidome on breast cancer: a Mendelian randomization study

Does androgenic alopecia aggravate the risk of prostate cancer? Evidence from Mendelian randomization

Associations Between Lipid Traits and Breast Cancer Risk: A Mendelian Randomization Study in African Women

Contact Info

Product

Resources

About