Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study

Background: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomised controlled trials (RCT) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.

Objective: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (beta-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6, vitamin B12 and zinc) with colorectal cancer risk using Mendelian randomization (MR).

Design: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the GECCO, CORECT and CCFR consortia. Inverse variance weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.

Results: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon (odds ratios per standard deviation [ORSD]: 1.08, 95% confidence interval [CI]: 1.00, 1.17, P-value: 0.05) and similarly for proximal colon cancer, and for vitamin B12 concentration and higher risk of colorectal (ORSD: 1.12, 95% CI: 1.03, 1.21, P-value: 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon (ORSD: 0.98, 95% CI: 0.96, 1.00, P-value: 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. A nominally significant inverse association was observed for zinc and risk of colorectal and distal colon cancer, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of beta-carotene, calcium, copper, folate, magnesium, phosphorus and vitamin B6 were not associated with disease risk.

Conclusions: These results suggest possible causal associations of circulating iron and vitamin B12 (positively) and selenium (inversely) with risk of colon cancer.