Dong Huke, Zhang Chen, Wang Hua, Dai Ying
Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Lu'an Hospital of Traditional Chinese Medicine, Lu'an, China.
Discov Oncol. 2025 May 13;16(1):745. doi: 10.1007/s12672-025-02541-z.
S. Plasma lipids in circulation are integral to the physiopathological processes of the ovary and may impact the development of various ovarian conditions, including ovarian cancer (OC). This study utilized a two-sample Mendelian randomization method to examine the causal link between changes in 179 plasma lipid groups and ovarian cancer (OC) to gain deeper insights into this association. We used the inverse variance weighted (IVW) method as the main tool for analysis. We utilized statistical data from plasma lipidomics involving 7,174 Finnish individuals and OC data from the FinnGen consortium, including 2,339 European OC patients and 222,078 European healthy controls. Our analysis revealed that elevated levels of four plasma lipids-Phosphatidylcholine (14:0_16:0, O-18:2_18:2, 16:0_20:4)-are linked to an increased risk of OC, while Sphingomyelin (d34:2) seems to act as a protective factor(all P < 0.05). We also conducted tests for heterogeneity and pleiotropy in the MR results. Additionally, reverse MR analysis indicated that OC does not affect plasma levels of these lipids. To determine whether the observed significant plasma lipids influence OC through common risk factors, we selected BMI as a confounder for multivariable Mendelian randomization (MVMR) analysis. The results showed that Sphingomyelin (d34:2) levels remained significantly associated with OC even after including BMI as an exposure factor. Furthermore, we investigated whether these four lipids mediated the effect of BMI on OC but found no evidence supporting their mediating role. In summary, our findings confirm a causal link between certain plasma lipid species and OC, providing fresh perspectives for risk evaluation and potential therapeutic strategies.
循环中的血浆脂质是卵巢生理病理过程不可或缺的一部分，可能会影响包括卵巢癌（OC）在内的各种卵巢疾病的发展。本研究采用两样本孟德尔随机化方法，研究179种血浆脂质组变化与卵巢癌（OC）之间的因果关系，以更深入地了解这种关联。我们使用逆方差加权（IVW）方法作为主要分析工具。我们利用了来自7174名芬兰人的血浆脂质组学统计数据和来自芬兰基因联盟的OC数据，包括2339名欧洲OC患者和222078名欧洲健康对照。我们的分析表明，四种血浆脂质水平升高——磷脂酰胆碱（14:0_16:0、O-18:2_18:2、16:0_20:4）——与OC风险增加有关，而鞘磷脂（d34:2）似乎起到保护作用（所有P<0.05）。我们还对MR结果进行了异质性和多效性检验。此外，反向MR分析表明OC不会影响这些脂质的血浆水平。为了确定观察到的显著血浆脂质是否通过共同危险因素影响OC，我们选择BMI作为多变量孟德尔随机化（MVMR）分析的混杂因素。结果表明，即使将BMI作为暴露因素纳入，鞘磷脂（d34:2）水平仍与OC显著相关。此外，我们研究了这四种脂质是否介导BMI对OC的影响，但没有发现支持它们介导作用的证据。总之，我们的研究结果证实了某些血浆脂质种类与OC之间的因果关系，为风险评估和潜在治疗策略提供了新的视角。
