Liu Ting, Tuo Xiaoqian, Zhao Huifang, Wang Yan, Jiang Yu, Lu Jiaojiao
Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China.
Department of Gynecology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710061, People's Republic of China.
J Ovarian Res. 2025 Aug 1;18(1):173. doi: 10.1186/s13048-025-01733-z.
BACKGROUND: Ovarian cancer could induce alterations in both structure and function of the brain. This study employs Mendelian randomization (MR) to investigate the causal relationship between brain imaging-derived phenotypes (IDPs) and ovarian cancer, offering new insights into the potential clinical applications of IDPs for ovarian cancer risk assessment. METHODS: This study identified 587 brain IDPs using structural and diffusion magnetic resonance imaging (MRI) data from the UK Biobank and data were sourced from two independent Genome-Wide Association Studies (GWAS). We selected single nucleotide polymorphisms (SNPs) as instrumental variables based on rigorous criteria. To evaluate the causal effects of IDPs on the risk of ovarian cancer, we employed five MR models: Inverse Variance Weighted (IVW), MR-Egger regression, Weighted median, Weighted mode, and Simple mode. Furthermore, we conducted a meta-analysis to provide additional validation for our results. RESULTS: Forward MR analysis identified 72 IDPs that were significantly associated with the risk of ovarian cancer, with 65 remaining robust after conducting sensitivity tests. Conversely, reverse MR analysis indicated that 63 IDPs were influenced by ovarian cancer, highlighting a bidirectional causal relationship between these factors. The meta-analysis revealed that an increased cortical surface area of the right precentral gyrus was associated with a heightened risk of ovarian cancer, with an odds ratio (OR) of 1.139 (95% confidence interval [CI]: 1.037-1.250, P = 0.006, common effect model). In contrast, a larger volume of the right medial orbital frontal cortex was linked to a reduced risk of ovarian cancer, with an OR of 0.839 (95% CI: 0.744-0.946, P = 0.004, common effect model). Additionally, in the reverse MR analysis, a higher risk of ovarian cancer was associated with an increased fractional anisotropy (FA) in the right fornix and stria terminalis, while decreased orientation dispersion index (OD) in the left anterior corona radiata. CONCLUSIONS: This study provides compelling evidence of a causal relationship between IDPs and ovarian cancer risk. It suggests that IDPs might serve as valuable biomarkers for ovarian cancer risk assessment at brain-imaging levels and emphasize the need for further research to explore the biological mechanisms underlying these associations.
背景：卵巢癌可导致大脑结构和功能的改变。本研究采用孟德尔随机化方法（MR）来探究源自脑成像的表型（IDPs）与卵巢癌之间的因果关系，为IDPs在卵巢癌风险评估中的潜在临床应用提供新见解。 方法：本研究利用英国生物银行的结构和扩散磁共振成像（MRI）数据识别出587个脑IDPs，数据来源于两项独立的全基因组关联研究（GWAS）。我们基于严格标准选择单核苷酸多态性（SNPs）作为工具变量。为评估IDPs对卵巢癌风险的因果效应，我们采用了五种MR模型：逆方差加权法（IVW）、MR-Egger回归、加权中位数法、加权众数法和简单模式法。此外，我们进行了荟萃分析以对结果提供额外验证。 结果：正向MR分析确定了72个与卵巢癌风险显著相关的IDPs，在进行敏感性测试后，其中65个仍然稳健。相反，反向MR分析表明63个IDPs受卵巢癌影响，突出了这些因素之间的双向因果关系。荟萃分析显示，右侧中央前回皮质表面积增加与卵巢癌风险升高相关，优势比（OR）为1.139（95%置信区间[CI]：1.037 - 1.250，P = 0.006，固定效应模型）。相反，右侧眶额内侧皮质体积较大与卵巢癌风险降低相关，OR为0.839（95% CI：0.744 - 0.946，P = 0.004，固定效应模型）。此外，在反向MR分析中，卵巢癌风险较高与右侧穹窿和终纹的分数各向异性（FA）增加相关，而左侧放射冠前部的方向离散指数（OD）降低。 结论：本研究提供了IDPs与卵巢癌风险之间因果关系的有力证据。这表明IDPs可能作为脑成像水平上卵巢癌风险评估的有价值生物标志物，并强调需要进一步研究以探索这些关联背后的生物学机制。
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