Ansah Emmanuel Owusu, Kyei Foster, Opoku Caleb Frimpong, Danquah Andrews, Fosu Kwadwo, Agyenim Emmanuel Boateng, Agyirifo Daniel Sakyi
Department of Molecular Biology and Biotechnology, University of Cape Coast, Cape Coast, Ghana.
Gene Therapy Programme, Thrivus Institute for Biomedical Science and Technology, Cape Coast, Ghana.
Cancer Med. 2025 May;14(9):e70928. doi: 10.1002/cam4.70928.
Blood lipids are implicated in the development of breast cancer (BC), though the genetic connection remains unclear, particularly in African populations. Observational studies on this topic are limited by confounding factors and reverse causation, potentially affecting the reliability of findings.
We applied univariate and multivariable two-sample Mendelian randomization to assess the causal association between blood lipids (total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides [TG]) and BC. Summary-level data for lipid traits were sourced from the Africa Wits-INDEPTH partnership for Genomic Research (AWI-Gen) (N = 10,603 women). BC data were obtained from the largest genome-wide association study of BC in African women, comprising 18,034 BC cases and 22,104 controls.
Our analysis revealed that genetically predicted TG was associated with a decreased BC risk (OR = 0.73, 95% CI = 0.56-0.95, p = 0.018. In contrast, no significant associations were found between TC, HDL, or LDL levels and BC risk: TC (OR = 1.04, 95% CI = 0.93-1.18, p = 0.467), HDL (OR = 1.29, 95% CI = 0.93-1.79, p = 0.121), and LDL (OR = 1.04, 95% CI = 0.90-1.20, p = 0.577). After adjusting for the effects of other lipid traits, the association between TG and BC was attenuated, and no associations were observed for TC, HDL, or LDL. No causal relationship was found between lipid traits and BC subtypes.
This study provides evidence that elevated triglycerides may be associated with a reduced risk of BC, whereas no significant associations were observed for TC, HDL, or LDL. Further research is needed to better understand the underlying mechanisms and potential clinical implications of these findings.
血脂与乳腺癌（BC）的发生有关，尽管基因关联尚不清楚，尤其是在非洲人群中。关于这一主题的观察性研究受到混杂因素和反向因果关系的限制，可能会影响研究结果的可靠性。
我们应用单变量和多变量两样本孟德尔随机化方法来评估血脂（总胆固醇[TC]、高密度脂蛋白[HDL]、低密度脂蛋白[LDL]和甘油三酯[TG]）与BC之间的因果关联。血脂性状的汇总数据来自非洲维特沃特斯兰德大学深度基因组研究合作项目（AWI-Gen）（N = 10603名女性）。BC数据来自非洲女性中最大规模的BC全基因组关联研究，包括18034例BC病例和22104例对照。
我们的分析显示，基因预测的TG与BC风险降低相关（OR = 0.73，95%CI = 0.56 - 0.95，p = 0.018）。相比之下，未发现TC、HDL或LDL水平与BC风险之间存在显著关联：TC（OR = 1.04，95%CI = 0.93 - 1.18，p = 0.467），HDL（OR = 1.29，95%CI = 0.93 - 1.79，p = 0.121），以及LDL（OR = 1.04，95%CI = 0.90 - 1.20，p = 0.577）。在调整其他血脂性状的影响后，TG与BC之间的关联减弱，且未观察到TC、HDL或LDL的关联。未发现血脂性状与BC亚型之间存在因果关系。
本研究提供的证据表明，甘油三酯升高可能与BC风险降低相关，而未观察到TC、HDL或LDL有显著关联。需要进一步研究以更好地理解这些发现的潜在机制和临床意义。
