Complex Role of Circulating Triglycerides in Breast Cancer Onset and Survival: Insights From Two-Sample Mendelian Randomization Study

IF 3.1 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2025-02-17 DOI:10.1002/cam4.70698

Wu Zhang, Zhiru Li, Yuquan Huang, Jing Zhao, Shaowei Guo, Qian Wang, Sihan Guo, Qingxia Li

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Abstract

Background

Reducing the incidence of breast cancer and improving its prognosis have become significant challenges for the global public health sector. We aimed to investigate the role of circulating triglycerides in the occurrence and survival of patients with breast cancer, while focusing on the possible differential effects by molecular subtypes of breast cancer.

Methods

We used a Mendelian randomization approach to analyze publicly accessible genome-wide association study data, including triglyceride levels, breast cancer risk, and survival prognosis. We performed a two-sample causality inference analysis using the inverse-variance weighted method. We used both Mendelian randomization–Egger regression and weighted median methods for model verification. Heterogeneity was evaluated using Cochran's Q test, and sensitivity analyses were performed using the leave-one-out method, Mendelian randomization–Egger intercept test, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier test.

Results

The results revealed a negative causal relationship between triglyceride levels and overall breast cancer risk (odds ratio [OR] = 0.94, confidence interval [CI] = 0.89–0.99, p = 0.011), luminal A breast cancer risk (OR = 0.93, CI = 0.87–0.99, p = 0.014), and human epidermal growth factor receptor 2 (HER2)-enriched breast cancer risk (OR = 0.84, CI = 0.73–0.96, p = 0.010). However, no statistically significant correlations were observed for the luminal B, luminal B HER2-negative, and triple-negative subtypes. Furthermore, triglyceride levels showed a positive causal relationship with the risk of survival prognosis in patients with estrogen receptor-negative breast cancer (OR = 1.33, CI = 1.00–1.76, p = 0.047). However, no statistically significant impact was observed on the survival of patients with overall breast cancer or patients with estrogen receptor-positive, HER2-positive, and HER2-negative breast cancer.

Conclusions

The potentially complex role of circulating triglycerides in the incidence and survival of patients with breast cancer provides a new perspective on the heterogeneity of the effects of triglycerides on breast cancer, thereby promoting the development of precise medical strategies. Moreover, our findings contribute to an increased understanding of overall health among patients and clinicians alike.

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循环甘油三酯在乳腺癌发病和生存中的复杂作用：来自两样本孟德尔随机化研究的见解

背景减少乳腺癌的发病率和改善其预后已成为全球公共卫生部门面临的重大挑战。我们的目的是研究循环甘油三酯在乳腺癌患者的发生和生存中的作用，同时关注乳腺癌分子亚型可能产生的差异效应。方法采用孟德尔随机化方法分析可公开获取的全基因组关联研究数据，包括甘油三酯水平、乳腺癌风险和生存预后。我们使用反方差加权方法进行了双样本因果推理分析。我们使用孟德尔随机化-艾格回归和加权中位数方法进行模型验证。采用Cochran’s Q检验评估异质性，采用留一法、孟德尔随机化- egger截距检验、孟德尔随机化多效差和和离群值检验进行敏感性分析。结果结果显示，甘油三酯水平与总体乳腺癌风险（比值比[OR] = 0.94，置信区间[CI] = 0.89-0.99, p = 0.011）、luminal a乳腺癌风险（OR = 0.93, CI = 0.87-0.99, p = 0.014）、人表皮生长因子受体2 （HER2）富集乳腺癌风险（OR = 0.84, CI = 0.73-0.96, p = 0.010）呈负相关。然而，在管腔B、管腔B her2阴性和三阴性亚型之间没有观察到统计学上显著的相关性。此外，甘油三酯水平与雌激素受体阴性乳腺癌患者生存预后风险呈正相关（OR = 1.33, CI = 1.00-1.76, p = 0.047）。然而，对整体乳腺癌患者或雌激素受体阳性、her2阳性和her2阴性乳腺癌患者的生存率没有统计学上显著的影响。结论循环甘油三酯在乳腺癌患者发病率和生存中的潜在复杂作用为甘油三酯对乳腺癌影响的异质性提供了新的视角，从而促进了精准医疗策略的发展。此外，我们的发现有助于提高患者和临床医生对整体健康的理解。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.