Circulating concentrations of micro-nutrients and risk of breast cancer: A Mendelian randomization study

Abstract Background The epidemiological literature reports inconsistent associations between consumption or circulating concentrations of micro-nutrients and breast cancer risk. We investigated associations between genetically determined 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). Materials and methods A two-sample MR study was conducted using 122,977 women with breast cancer, of whom 69,501 were estrogen receptor positive (ER +ve ) and 21,468 were ER −ve , 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. Results One standard deviation (SD: 0.08 mmol/L) higher genetically determined concentration of magnesium was associated with a 17% (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.10 to 1.25, P =9.1 × 10 −7 ) and 20% (OR: 1.20, 95% CI: 1.11 to 1.30, P =3.17 × 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 determined phosphorus concentration and ER −ve breast cancer (OR: 0.84, 95% CI: 0.72 to 0.98, P =0.03). A suggestive inverse association was observed for a SD (0.48 mg/dL) higher genetically determined calcium concentration with overall breast cancer (OR: 0.91, 95% CI: 0.83 to 1.00, P =0.06). There was little evidence that any of the other nutrients were associated with breast cancer. The results for magnesium were robust under all sensitivity analyses. Conclusions Higher circulating concentrations of magnesium, phosphorus and calcium may affect breast cancer risk. Further work is required to replicate these findings and investigate underlying mechanisms. key message We conducted a Mendelian randomization study to investigate whether 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 higher concentrations of magnesium and inverse associations were observed for phosphorus and calcium concentrations Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.