Abstract
To determine the causality of micro-nutrients concentrations and risk of ovarian cancer using the Mendelian randomization approach. Analyses were conducted using summary statistics data for SNPs robustly associated with concentrations of thirteen micro-nutrients (iron, copper, zinc, calcium, magnesium, phosphorus, selenium, vitamin A, β-carotene, vitamin B6, vitamin B12, vitamin E, folate). The corresponding data for ovarian cancer were obtained from the Ovarian Cancer Association Consortium (25,509 cases and 40,941 controls). In standard Mendelian randomization analysis, the odds ratios (OR) of invasive epithelial ovarian cancer were 0.14 (95% CI, 0.03-0.70; P = 0.02) per 0.1 mmol/L (about one standard deviation, SD) increase in genetically predicted magnesium concentration, 1.04 (95% CI, 1.00-1.09; P = 0.03) per 0.3 μmol/liter (about one SD) increase in genetically predicted β-carotene concentration. The OR of low malignant potential tumours were 0.82 (95% CI, 0.76-0.90; P = 1.01 × 10(-5)) per 0.3 μmol/liter (about one SD) increase in β-carotene concentration, 1.42 (95% CI, 1.21-1.68; P = 3 × 10(-5)) per 153 pmol/L (about one SD) increase in vitamin B12 concentration, 0.21 (95% CI, 0.06-0.76; P = 0.02) per 6 mg/L (about one SD) increase in vitamin E concentration. No significant associations of other micro-nutrients and ovarian cancer were observed. This study found that an increased risk of invasive epithelial ovarian cancer was observed with a genetically higher concentration of β-carotene, whereas a decreased risk of invasive epithelial ovarian cancer was found with a higher concentration of magnesium. As for low malignant potential tumours, increased concentration of vitamin B12 could increase the risk of low malignant potential tumours, while increased concentrations of β-carotene and vitamin E could lower the risk of low malignant potential tumours.