Genetically predicted circulating concentrations of micronutrients and risk of breast cancer: A Mendelian randomization study.

Abstract

The epidemiological literature reports inconsistent associations between consumption or circulating concentrations of micronutrients and breast cancer risk. We investigated associations between genetically predicted concentrations of 11 micronutrients (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. A value of 1 SD (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]: 1.10-1.25, P value = 9.1 × 10-7 ) and 20% (OR: 1.20, 95% CI: 1.08-1.34, 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: 0.72-0.98, P value = .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.

• Authors: Nikos Papadimitriou, Niki Dimou, Dipender Gill, Ioanna Tzoulaki, Neil Murphy, Elio Riboli, Sarah J Lewis, Richard M Martin, Marc J Gunter, Konstantinos K Tsilidis
• Journal: International journal of cancer (Int J Cancer) Vol. 148 Issue 3 Pg. 646-653 (02 01 2021) ISSN: 1097-0215 [Electronic] United States
• PMID: 32761610 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Union for International Cancer Control.

Chemical References

• Micronutrients
• Receptors, Estrogen
• Phosphorus
• Magnesium

Topics

• Breast Neoplasms (blood, epidemiology, genetics)
• Case-Control Studies
• Female
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Magnesium (blood)
• Mendelian Randomization Analysis (methods)
• Micronutrients (blood)
• Molecular Epidemiology
• Phosphorus (blood)
• Polymorphism, Single Nucleotide
• Receptors, Estrogen (genetics)