Platelet count and breast cancer: Insights from Mendelian randomization

Breast cancer is a leading global malignancy in women, with limited genetic evidence for the association between platelet count and breast cancer risk. Aiming to provide genetic evidence for their relationship, this 2-sample Mendelian randomization (MR) study was conducted using datasets published in 2021 comprising platelet count (n = 148,623) and breast cancer (n = 79,550). The inverse-variance weighted (IVW), weighted median estimator (WME), MR-Egger, and Weighted mode methods were employed to evaluate the causal effect of platelet count on the risk of breast cancer. 97 single-nucleotide polymorphisms (SNPs) were identified as effective instrumental variables for studying the causal link between platelet count and breast cancer risk. The IVW method indicated that each standard deviation increase in platelet count raised breast cancer risk by 13.1% (odds ratio [OR] = 1.131, 95% confidence interval [CI] = 1.005-1.274, P = .042). The WME method found that a 1 standard deviation increase in platelet count raised breast cancer risk by 21.6% (OR = 1.216, 95% CI = 1.017-1.455, P = .032). While MR-Egger regression and Weighted mode results did not show a statistically significant causal link, the direction of the causal effect identified by both methods was consistent with the results obtained from the IVW and WME methods. The study provides evidence for a potential causal relationship between platelet count and the risk of breast cancer. Further investigations across diverse populations are warranted to validate these findings.