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

Breast cancer (BC), one of the most common cancers, has increased in Mexico during the past decade, along with other chronic and metabolic diseases. Herein, we analyzed 121 SNPs (92 previously associated SNPs to BC, type 2 diabetes, obesity, overweight, insulin resistance, inflammation, and 36 informative ancestry markers) in 91 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 by a gene-environment (G × E) interaction multi-locus model. Twelve gene variants were significantly associated with BC: rs3856806 PPARG, rs12792229 MMP8, and rs5218 KCNJ11-ABCC8. Whereas rs3917542 PON1; rs3750804 and rs3750805 TCF7L2; rs1121980 and rs3751812 FTO; rs12946618 RPTOR; rs2833483 SCAF4; rs11652805 AMZ2P1-GNA13; and rs1800955 SCT-DEAF1-DRD4 were located in non-coding regions, involved in the accelerated decay of the mRNA transcripts, regulatory, and flanking regions. This study corroborated the association of BC along with menopause, age (above 45), obesity, and overweight with gene variants implicated in diabetes mellitus, obesity, insulin resistance, inflammation, and remodeling of the extracellular matrix.