文章：

墨西哥东北部乳腺癌的遗传学洞察：揭示基因-环境相互作用及其与肥胖和代谢疾病的关联

Genetic Insights into Breast Cancer in Northeastern Mexico: Unveiling Gene–Environment Interactions and Their Links to Obesity and Metabolic Diseases

原文发布日期：14 March 2025

DOI: 10.3390/cancers17060982

类型: Article

开放获取: 是

英文摘要：

Background:Breast cancer (BC), one of the most common cancers, has increased in Mexico during the past decade, along with other chronic and metabolic diseases.Methods:Herein, we analyzed 121 SNPs (85 SNPs related to BC and/or glucose-associated metabolic pathways and 36 SNP classified as ancestry markers) in 92 confirmed BC cases and 126 unaffected BC women from Northeastern Mexico. The relationship of these 121 SNPs with BC, considering BMI, menopause status, and age as cofactors, was explored using a gene–environment (G × E) interaction multi-locus model.Results:Twelve gene variants were significantly associated with BC: three located in exome (rs3856806PPARG, rs12792229MMP8, and rs5218KCNJ11-ABCC8), and nine in non-coding regions, which are involved in accelerated decay of the mRNA transcripts, regulatory regions, and flanking regions (rs3917542PON1; rs3750804 and rs3750805TCF7L2; rs1121980 and rs3751812FTO; rs12946618RPTOR; rs2833483SCAF4; rs11652805AMZ2P1-GNA13; and rs1800955SCT-DEAF1-DRD4).Conclusions:This study identified an association between BC and menopause, age (above 45), obesity, and overweight status with gene variants implicated in diabetes mellitus, obesity, insulin resistance, inflammation, and remodeling of the extracellular matrix.

摘要翻译： 

背景：乳腺癌作为最常见的癌症之一，在过去十年间与其它慢性代谢性疾病在墨西哥的发病率同步上升。方法：本研究对来自墨西哥东北部的92例确诊乳腺癌患者及126名健康对照女性进行了121个单核苷酸多态性位点分析（其中85个位点与乳腺癌和/或糖代谢通路相关，36个位点作为祖先遗传标记）。通过基因-环境交互作用多基因座模型，在控制体重指数、绝经状态和年龄等协变量的条件下，探究了这些位点与乳腺癌的关联性。结果：共发现12个基因变异与乳腺癌显著相关：其中3个位于外显子区域（rs3856806PPARG、rs12792229MMP8和rs5218KCNJ11-ABCC8），其余9个位于非编码区域，涉及mRNA转录本加速降解、调控区及侧翼区域（rs3917542PON1；rs3750804和rs3750805TCF7L2；rs1121980和rs3751812FTO；rs12946618RPTOR；rs2833483SCAF4；rs11652805AMZ2P1-GNA13；以及rs1800955SCT-DEAF1-DRD4）。结论：本研究揭示了乳腺癌与绝经状态、年龄（45岁以上）、肥胖及超重之间的关联，并发现这些表型与涉及糖尿病、肥胖、胰岛素抵抗、炎症反应及细胞外基质重塑的基因变异存在显著相关性。

原文链接：

Genetic Insights into Breast Cancer in Northeastern Mexico: Unveiling Gene–Environment Interactions and Their Links to Obesity and Metabolic Diseases