# Genetic prediction of the casual relationship between micronutrients and ER+ breast cancer: a Mendelian randomized study

**Authors:** Wei-Da Fu, Jin-Qiu Wang, Jin Luo, Ming-Ze Wei, Yong-Ping Dai, He-He Wang

PMC · DOI: 10.3389/fgene.2025.1599724 · Frontiers in Genetics · 2025-07-23

## TL;DR

This study uses genetic data to find a link between vitamin B6 and increased risk of a common type of breast cancer.

## Contribution

The study identifies a novel causal link between genetically predicted vitamin B6 levels and ER+ breast cancer risk.

## Key findings

- Genetically predicted higher vitamin B6 levels are associated with increased ER+ breast cancer risk (OR: 1.275).
- No significant associations were found for the other 14 micronutrients and ER+ breast cancer risk.
- The study suggests a need for further research into the biological mechanisms linking vitamin B6 and ER+ breast cancer.

## Abstract

Estrogen receptor-positive (ER+) breast cancer, a prevalent subtype of breast malignancy, demonstrates complex etiological associations with multiple risk factors. Micronutrients, as essential nutritional components for human physiology, may potentially influence the pathogenesis and progression of breast carcinoma. This investigation employs Mendelian randomization (MR) methodology to assess causal relationships between 15 micronutrients and ER+ breast cancer.

In this study, instrumental variables (IVs) for 15 micronutrients were extracted from the genome-wide association studies (GWAS) database, including copper, calcium, carotene, folate, iron, magnesium, potassium, selenium, vitamin A, vitamin B12, vitamin B6, vitamin C, vitamin D, vitamin E, and zinc. Concurrently, summary data related to ER+ breast cancer were obtained from the FinnGen database. Following the selection of appropriate IVs, we conducted a two-sample MR analysis. This analytical framework incorporated comprehensive sensitivity analyses to evaluate potential heterogeneity and horizontal pleiotropy, with the inverse variance weighted (IVW) method established as the principal analytical approach.

The findings of our study revealed a significant causal relationship between vitamin B6 and ER+ breast cancer. Notably, genetically predicted elevated vitamin B6 levels were significantly associated with an increased risk of ER+ breast cancer [Odds Ratio (OR): 1.275; 95%Confidence Interval (CI): (1.017–1.600); P = 0.035]. In contrast, no statistically significant associations were observed between the other 14 micronutrients and ER+ breast cancer risk (P > 0.05 for all).

Our results indicated that higher concentrations of vitamin B6 may be positively associated with ER+ breast cancer risk, and further research is needed to elucidate the underlying biological mechanisms of this association. This study provides new insights into understanding the role of micronutrients in breast cancer.

## Linked entities

- **Chemicals:** vitamin B6 (PubChem CID 1054), copper (PubChem CID 23978), calcium (PubChem CID 5460341), carotene (PubChem CID 446925), folate (PubChem CID 135405876), iron (PubChem CID 23925), magnesium (PubChem CID 5462224), potassium (PubChem CID 813), selenium (PubChem CID 6326970), vitamin A (PubChem CID 445354), vitamin B12 (PubChem CID 73415824), vitamin B6 (PubChem CID 1054), vitamin C (PubChem CID 54670067), vitamin E (PubChem CID 14985), zinc (PubChem CID 23994)
- **Diseases:** ER+ breast cancer (MONDO:0006512), breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}
- **Diseases:** breast cancer (MESH:D001943)
- **Chemicals:** potassium (MESH:D011188), calcium (MESH:D002118), iron (MESH:D007501), vitamin B12 (MESH:D014805), vitamin B6 (MESH:D025101), vitamin C (MESH:D001205), vitamin D (MESH:D014807), copper (MESH:D003300), vitamin A (MESH:D014801), carotene (MESH:D002338), zinc (MESH:D015032), folate (MESH:D005492), vitamin E (MESH:D014810), selenium (MESH:D012643), magnesium (MESH:D008274)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12325068/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12325068/full.md

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Source: https://tomesphere.com/paper/PMC12325068