Fu Wei-Da, Wang Jin-Qiu, Luo Jin, Wei Ming-Ze, Dai Yong-Ping, Wang He-He
Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Front Genet. 2025 Jul 23;16:1599724. doi: 10.3389/fgene.2025.1599724. eCollection 2025.
Estrogen receptor-positive (ER+) breast cancer, a prevalent subtype of breast malignancy, demonstrates complex etiological associations with multiple risk factors. Micronutrients, as essential nutritional components for human physiology, may potentially influence the pathogenesis and progression of breast carcinoma. This investigation employs Mendelian randomization (MR) methodology to assess causal relationships between 15 micronutrients and ER+ breast cancer.
In this study, instrumental variables (IVs) for 15 micronutrients were extracted from the genome-wide association studies (GWAS) database, including copper, calcium, carotene, folate, iron, magnesium, potassium, selenium, vitamin A, vitamin B12, vitamin B6, vitamin C, vitamin D, vitamin E, and zinc. Concurrently, summary data related to ER+ breast cancer were obtained from the FinnGen database. Following the selection of appropriate IVs, we conducted a two-sample MR analysis. This analytical framework incorporated comprehensive sensitivity analyses to evaluate potential heterogeneity and horizontal pleiotropy, with the inverse variance weighted (IVW) method established as the principal analytical approach.
The findings of our study revealed a significant causal relationship between vitamin B6 and ER+ breast cancer. Notably, genetically predicted elevated vitamin B6 levels were significantly associated with an increased risk of ER+ breast cancer [Odds Ratio (OR): 1.275; 95%Confidence Interval (CI): (1.017-1.600); = 0.035]. In contrast, no statistically significant associations were observed between the other 14 micronutrients and ER+ breast cancer risk ( > 0.05 for all).
Our results indicated that higher concentrations of vitamin B6 may be positively associated with ER+ breast cancer risk, and further research is needed to elucidate the underlying biological mechanisms of this association. This study provides new insights into understanding the role of micronutrients in breast cancer.
雌激素受体阳性（ER+）乳腺癌是一种常见的乳腺恶性肿瘤亚型，与多种风险因素存在复杂的病因学关联。微量营养素作为人体生理必需的营养成分，可能会影响乳腺癌的发病机制和进展。本研究采用孟德尔随机化（MR）方法评估15种微量营养素与ER+乳腺癌之间的因果关系。
在本研究中，从全基因组关联研究（GWAS）数据库中提取了15种微量营养素的工具变量（IVs），包括铜、钙、胡萝卜素、叶酸、铁、镁、钾、硒、维生素A、维生素B12、维生素B6、维生素C、维生素D、维生素E和锌。同时，从芬兰基因数据库中获取了与ER+乳腺癌相关的汇总数据。在选择合适的IVs后，我们进行了两样本MR分析。该分析框架纳入了全面的敏感性分析，以评估潜在的异质性和水平多效性，并将逆方差加权（IVW）方法作为主要分析方法。
我们的研究结果显示维生素B6与ER+乳腺癌之间存在显著的因果关系。值得注意的是，基因预测的维生素B6水平升高与ER+乳腺癌风险增加显著相关[比值比（OR）：1.275；95%置信区间（CI）：（1.017 - 1.600）；P = 0.035]。相比之下，未观察到其他14种微量营养素与ER+乳腺癌风险之间存在统计学显著关联（所有P>0.05）。
我们的结果表明，较高浓度的维生素B可能与ER+乳腺癌风险呈正相关，需要进一步研究以阐明这种关联的潜在生物学机制。本研究为理解微量营养素在乳腺癌中的作用提供了新的见解。
