Genetically Predicted Circulating Levels of Antioxidants and Risk of Breast and Ovarian Cancer

Abstract

Abstract Evidence from observational studies for the effects of circulating antioxidants on the risk of breast and ovarian cancer was inconsistent. To elucidate the potential causal association of circulating antioxidants on the risk of breast and ovarian cancer, we carried out a two-sample Mendelian randomization (MR) study. The instrumental variables as proxies of genetic liability to circulating antioxidants were obtained from several published data. Summary-level data of breast and ovarian cancer were obtained from genome-wide association study (GWAS) conducted by the Breast (122,977 cases and 105,974 controls) and the Ovarian (25,509 cases and 40,941 controls) Cancer Association Consortiums. MR analyses were mainly performed using the inverse variance–weighted tests. Sensitivity analyses were further conducted to assess heterogeneity and horizontal pleiotropy. No evidence of causal association between genetically predicted circulating antioxidants and breast cancer and its histotypes was discovered as assessed by absolute levels [β-carotenoid: OR, 0.98; 95% confidence interval (CI), 0.92–1.05; P = 0.627; lycopene: OR, 0.99; 95% CI, 0.95–1.03; P = 0.532; retinol: OR, 0.87; 95% CI, 0.49–1.55; P = 0.645; ascorbate: OR, 1.00; 95% CI, 0.99–1.00; P = 0.123] and metabolites (α-tocopherol: OR, 0.88; 95% CI, 0.65–1.19; P = 0.394; γ-tocopherol: OR, 1.00; 95% CI, 0.87–1.16; P = 0.978; retinol: OR, 1.02; 95% CI, 1.00–1.04; P = 0.070; ascorbate: OR, 0.99; 95% CI, 0.91–1.06; P = 0.703). Similarly, no beneficial effect of genetic determinants of circulating antioxidants on ovarian cancer and its histotypes was found. Our study might not indicate a protective role of circulating antioxidants on the breast or ovarian cancer risk. Prevention Relevance: Although this study does not find that circulating antioxidants are protective against breast and ovarian cancer, it is still possible that a high intake of antioxidant-rich foods containing other potentially beneficial components could be cancer preventative.