Genetically predicted circulating concentrations of micro-nutrients and risk of breast cancer: A Mendelian randomization study

Nikos Papadimitriou, Niki L Dimou, Dipender Gill, Ioanna Tzoulaki, Neil Murphy, Elio Riboli, Sarah J Lewis, Richard M Martin, Marc J Gunter, K. Tsilidis*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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.
Original languageEnglish
Pages (from-to)646-653
Number of pages8
JournalInternational Journal of Cancer
Volume148
Issue number3
Early online date25 Aug 2020
DOIs
Publication statusPublished - 15 Dec 2020

Structured keywords

  • ICEP

Keywords

  • breast cancer
  • causal inference
  • diet
  • Mendelian randomization
  • nutrition

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