Metabolic Disorders Research Center, Endocrinology and Metabolism Research Institute, North Kargar Ave, Tehran, Iran.
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Breast Cancer Res Treat. 2024 Feb;204(1):159-169. doi: 10.1007/s10549-023-07188-4. Epub 2023 Dec 9.
Breast cancer (BC), obesity, and type 2 diabetes mellitus (T2DM) are three complex diseases and health problems that are prevalent worldwide. The aim of this study was to investigate the common genetic associations between these diseases by referring back to the previous genome-wide association studies (GWAS).
To this end, significant GWAS variants and common variants associated with BC, obesity, or diabetes were identified from the GWAS catalog. To perform candidate variants, the 1000-Genomes Project was used to find variants with linkage disequilibrium. Common variants between each category were identified (common candidate haplotypic variants). Finally, these variants and their associated genes were examined for SNP function analysis, gene expression, gene-gene correlation, and pathway analysis.
The results identified 7 variants associated with both T2DM and BC, 8 variants associated with both obesity and BC, and 167 variants associating obesity with T2DM. 91 variants and 4 haplotypic blocks such as CTC were identified on the FTO gene associated with obesity, BC, and T2DM. The results of TCGA data showed that FTO in gene expression was correlated with 6 other genes in the DNA repair pathway in BC subjects.
This study suggests that the FTO gene is one of the major genes shared by BC, T2DM, and obesity based on two DNA repair and inflammatory mechanisms. These results may provide a new perspective on the important role of the FTO gene and repair mechanism in the relationship between BC, obesity, and T2DM for future studies.
乳腺癌（BC）、肥胖和 2 型糖尿病（T2DM）是三种复杂的疾病和健康问题，在全球范围内普遍存在。本研究旨在通过参考之前的全基因组关联研究（GWAS）来研究这些疾病之间常见的遗传关联。
为此，从 GWAS 目录中确定了与 BC、肥胖或糖尿病相关的显著 GWAS 变体和常见变体。为了进行候选变体分析，使用 1000 基因组计划来寻找具有连锁不平衡的变体。确定了每个类别之间的常见变体（常见候选单倍型变体）。最后，对这些变体及其相关基因进行 SNP 功能分析、基因表达、基因-基因相关性和途径分析。
结果确定了 7 个与 T2DM 和 BC 都相关的变体，8 个与肥胖和 BC 都相关的变体，以及 167 个与肥胖和 T2DM 相关的变体。在与肥胖、BC 和 T2DM 相关的 FTO 基因上鉴定出 91 个变体和 4 个单倍型块，如 CTC。TCGA 数据的结果表明，BC 受试者中 FTO 基因的表达与 DNA 修复途径中的其他 6 个基因相关。
本研究表明，基于两种 DNA 修复和炎症机制，FTO 基因是 BC、T2DM 和肥胖共有的主要基因之一。这些结果可能为未来研究中 FTO 基因和修复机制在 BC、肥胖和 T2DM 之间的重要作用提供新的视角。
