Authors
Rumeysa Adiyil, Murat Ihlamur
Published in
Clinical nutrition ESPEN. Pages 105227. Nov 03, 2026. Epub Nov 03, 2026.
Abstract
Breast cancer risk and progression are shaped by interactions between inherited genetic susceptibility and modifiable exposures, including diet. Nutrigenetic and nutrigenomic evidence suggests that germline variants can modify biological responses to nutrients and bioactive food compounds, potentially affecting pathways central to carcinogenesis. This narrative review synthesizes evidence across three distinct but complementary domains: (i) germline genotype-diet associations, (ii) nutrient-responsive molecular pathway modulation, and (iii) nutrition-related effects in defined tumor molecular phenotypes. These domains are evaluated separately to avoid equating inherited nutrigenetic interactions with preclinical pathway effects or somatic tumor characteristics.
A structured narrative literature search was conducted in PubMed, Web of Science, and Scopus for peer-reviewed English-language studies published up to 30 July 2026. Search terms combined breast cancer with nutrigenetics, nutrigenomics, gene-diet interactions, genetic variants, nutrient-responsive pathways, and the specific genes and dietary exposures covered in this review. Experimental, observational, and clinical/intervention studies were included when they directly addressed gene-diet interactions or nutrition-responsive molecular mechanisms relevant to breast cancer. The evidence was synthesized qualitatively according to study design and biological pathway.
Within the germline nutrigenetic domain, the most direct human evidence involved BRCA1/2, COMT, CYP17A1, GST-family genes, MTHFR, and selected FTO variants, although formal interaction testing and replication were inconsistent. Evidence concerning TP53 and FOXO3 was predominantly mechanistic or preclinical and was therefore interpreted as nutrient-responsive pathway modulation rather than as an established germline gene-diet interaction. HER2-positive breast cancer, characterized clinically by ERBB2 amplification and/or HER2 overexpression, was considered separately as a somatic tumor phenotype and treatment-relevant signaling context rather than as an inherited nutritional genotype. Across these domains, nutrients and bioactive compounds-including folate and B vitamins, vitamin D, polyphenols, phytoestrogens, crucifer-derived isothiocyanates, fatty acids, and Mediterranean-style dietary patterns-have been associated with genomic stability, hormone signaling, oxidative stress, epigenetic regulation, and metabolic pathways, but the type and strength of evidence differ substantially across genetic, molecular, and tumor-phenotype contexts. However, clinical translation remains constrained by heterogeneous populations, variable dietary assessment and exposure definitions, limited biomarker standardization, and a paucity of adequately powered genotype-stratified dietary trials.
Current evidence supports further investigation of genotype-aware and tumor-context-aware nutrition, but remains insufficient for routine genotype-based or tumor-phenotype-based dietary prescriptions. Future studies should clearly distinguish germline interaction effects from nutrient-responsive molecular mechanisms and tumor phenotypes while integrating standardized dietary exposures, validated biomarkers, and multi-omics approaches.
PMID:
42977159
Bibliographic data and abstract were imported from PubMed on 04 Nov 2026.
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