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

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. What's new? The epidemiological literature reports inconsistent associations between the consumption or circulating concentrations of micro‐nutrients and breast cancer risk. Evidence from clinical trials is also lacking. Here, the authors conducted a Mendelian randomization study to investigate whether genetically‐predicted concentrations of 11 micro‐nutrients are associated with risk of breast cancer. An increased risk of overall and oestrogen‐receptor positive disease was observed for genetically‐predicted higher concentrations of magnesium that was robust to sensitivity analyses and correction for multiple comparisons.