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Eurasian Journal of Medicine

                                                                                    and Oncology





                                        ORIGINAL RESEARCH ARTICLE
                                        The association between Vitamin D and breast

                                        cancer: A two-sample Mendelian randomization
                                        study



                                        Yang Xiao 1  , Mei Yin 2  , and Xingyi Song *
                                                                            2
                                        1 Department of Breast and  Thyroid Surgery, Peking University Shenzhen Hospital, Shenzhen,
                                        Guangdong, China
                                        2 Department of Humanities and Social Sciences, Harbin Medical University, Harbin, Heilongjiang,
                                        China



                                        Abstract

                                        Introduction: Breast cancer, as a significant threat to women’s health globally, has
                                        a complex pathogenesis. Vitamin D, a steroid hormone with diverse physiological
                                        functions, has garnered increasing attention in breast cancer research. Numerous
                                        studies have been conducted to elucidate the relationship between Vitamin D and
                                        breast cancer, yet no definitive conclusions have been reached. Objective: Hence, in
                                        this study, we conducted a two-sample Mendelian randomization (MR) analysis to
                                        investigate the association between Vitamin D and breast cancer.
                                        Methods: Genetic variants associated with Vitamin D levels and breast cancer data
                                        were obtained from the genome-wide association study database and version R11 of
            *Corresponding author:      the FinnGen study dataset, respectively. The inverse variance-weighted (IVW) method
            Xingyi Song                 served as the primary analytical approach, supplemented by various sensitivity
            (xy19460809@163.com)        analyses. Horizontal pleiotropy was tested using MR-Egger and MR-Pleiotropy
            Citation: Xiao Y, Yin M, Song X.   RESidual Sum and Outlier methods, while sensitivity analysis was conducted using
            The association between Vitamin   the leave-one-out method to assess the reliability of the results.
            D and breast cancer: A two-sample
            Mendelian randomization study.   Results: Based on instrumental variable assumptions, 111 single nucleotide
            Eurasian J Med Oncol.       polymorphisms were suitable for subsequent analyses after matching the results.
            2025;9(3):100-109.          The MR analysis demonstrated no evidence of a causal relationship between Vitamin
            doi: 10.36922/EJMO025130064  D and breast cancer. The IVW method yielded a non-significant association (p=0.968;
            Received: March 24, 2025    odds ratio = 1.002, 95% confidence interval: 0.896 – 1.119), and the other methods
            Revised: April 5, 2025      pointed out the same direction of effect, and the subsequent pleiotropic analysis and
                                        sensitivity analysis confirmed the accuracy of the results.
            Accepted: April 16, 2025    Conclusion:  At the genetic level, no causal relationship between Vitamin D and
            Published online: May 14, 2025  breast cancer was found; thus, our findings do not support a clinically significant role
            Copyright: © 2025 Author(s).   of Vitamin D supplementation in breast cancer risk reduction
            This is an Open-Access article
            distributed under the terms of the
            Creative Commons Attribution   Keywords: Vitamin D; Breast cancer; Mendelian randomization
            License, permitting distribution,
            and reproduction in any medium,
            provided the original work is
            properly cited.             1. Introduction
            Publisher’s Note: AccScience   Breast cancer, as one of the most common cancers, is one of the leading causes of death
            Publishing remains neutral with   for women worldwide.  Over the past 20 years, breast cancer rates have continued to
                                                          1
            regard to jurisdictional claims in            2
            published maps and institutional   rise in most countries.  In 2022, there were approximately 2.309 million new cases of
            affiliations.               breast cancer globally, ranking second among all cancers, with a corresponding crude

            Volume 9 Issue 3 (2025)                        100                         doi: 10.36922/EJMO025130064
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