Fast walking reduces the risk of breast cancer: evidence from a Mendelian randomisation study

Breast cancer is a prevalent malignancy that poses a serious threat to women's health. Lifestyle modifications can alter the risk of breast cancer. Walking is a common lifestyle behaviour, but its impact on breast cancer remains unclear. We conducted a Mendelian randomisation (MR) study to explore this issue. Independent genetic variants closely associated with usual walking speed were selected as instrumental variables from publicly available genome-wide association studies (GWAS) databases. Genetic data on the estrogen receptor (ER) status of breast cancer and breast cancer were obtained from a large-scale GWAS meta-analysis. Inverse variance-weighted regression analysis revealed that brisk walking speed was associated with a lower risk of breast cancer [OR = 0.69; 95%CI = (0.54, 0.88); P = 0.006] and lower risk of ER- breast cancer [OR = 0.60; 95%CI = (0.38, 0.91); P = 0.018]. However, walking speed was not associated with the risk of ER + breast cancer [OR = 0.92; 95%CI = (0.70, 1.25); P = 0.641]. MR-Egger intercept and MR-PRESSO tests did not reveal significant levels of pleiotropy or heterogeneity, respectively. Sensitivity analyses also confirmed the robustness of the results. Our study provides strong evidence that faster walking speeds may reduce the risk of breast cancer and that a more widespread adoption of moderate or high-intensity exercise may be effective in reducing women's health risks.