Genetically predicted circulating concentrations of micro-nutrients and risk of breast cancer: A Mendelian randomization study
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Accepted version
Author(s)
Type
Journal Article
Abstract
The epidemiological literature reports inconsistent associations between consumption or circulating concentrations of micro-nutrients and breast cancer risk. We investigated associations between genetically predicted concentrations of 11 micro-nutrients (beta-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6, vitamin B12 and zinc) and breast cancer risk using Mendelian randomization (MR). A two-sample MR study was conducted using 122,977 women with breast cancer and 105,974 controls from the Breast Cancer Association Consortium. MR analyses were conducted using the inverse variance weighted approach, and sensitivity analyses were conducted to assess the impact of potential violations of MR assumptions. One standard deviation (SD: 0.08 mmol/L) higher genetically predicted concentration of magnesium was associated with a 17% (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.10 to 1.25, P-value=9.1 ×10-7 ) and 20% (OR: 1.20, 95% CI: 1.08 to 1.34, P-value=3.2×10-6 ) higher risk of overall and ER+ve breast cancer, respectively. An inverse association was observed for a SD (0.5 mg/dL) higher genetically predicted phosphorus concentration and ER-ve breast cancer (OR: 0.84, 95% CI: 0.72 to 0.98, P-value=0.03). There was little evidence that any other nutrient was associated with breast cancer. The results for magnesium were robust under all sensitivity analyses and survived correction for multiple comparisons. Higher circulating concentrations of magnesium and potentially phosphorus may affect breast cancer risk. Further work is required to replicate these findings and investigate underlying mechanisms.
Date Issued
2021-02-01
Date Acceptance
2020-07-27
Citation
International Journal of Cancer, 2021, 148 (3), pp.646-653
ISSN
0020-7136
Publisher
Wiley
Start Page
646
End Page
653
Journal / Book Title
International Journal of Cancer
Volume
148
Issue
3
Copyright Statement
© 2020 Union for International Cancer Control. This is the peer reviewed version of the following article, which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.33246. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Sponsor
World Cancer Research Fund International
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/32761610
Grant Number
n/a
Subjects
Mendelian randomization
breast cancer
causal inference
diet
nutrition
Publication Status
Published online
Coverage Spatial
United States
Date Publish Online
2020-08-05