Effect of genetic liability to migraine and its subtypes on breast cancer: a mendelian randomization study

Abstract

Background The relationship between migraine and breast cancer risk has generated conflicting findings. We attempted to assess the association between migraine and breast cancer risk using Mendelian randomization (MR) analysis. Methods We selected genetic instruments associated with migraine from a recently published genome-wide association studies (GWAS). Inverse variant weighted (IVW) analysis was adopted as the main method, and we also performed the weighted-median method and the MR‒Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR Robust Adjusted Profile Score (MR-RAPS) methods as supplements. Results Our MR suggested that any migraine (AM) was a risk factor for overall breast cancer (IVW: odds ratio (OR) = 1.072, 95% confidence intervals (CI) = 1.035–1.110, P = 8.78 × 10− 5, false discovery rate (FDR) = 7.36 × 10− 4) and estrogen receptor-positive (ER+) breast cancer (IVW: OR = 1.066, 95% CI = 1.023–1.111, P = 0.0024; FDR = 0.0108) but not estrogen receptor-negative (ER-) breast cancer. In its subtype analysis, women with a history of migraine without aura (MO) had an increased risk of ER- breast cancer (IVW: OR = 1.089, 95% CI = 1.019–1.163, P = 0.0118, FDR = 0.0354), and MO was suggestively associated with the risk of overall breast cancer (FDR > 0.05 and IVW P < 0.05). No significant heterogeneity or horizontal pleiotropy was found in the sensitivity analysis. Conclusion This study suggested that women with AM have an increased risk of overall breast cancer and ER + breast cancer. MO was suggestively associated with the risk of overall breast cancer and ER- breast cancer.