Causal effects of blood cells on breast cancer: Evidence from bidirectional Mendelian randomization combined with...

Recent studies suggest blood cells influence breast cancer, but no Mendelian randomization (MR) studies have confirmed a causal relationship between specific blood cell phenotypes and breast cancer. MR analysis of blood cell phenotypes used breast cancer data from Finngen R11, UKB, and open genome-wide association study databases. Meta-analyzed inverse variance weighted results were adjusted for multiple comparisons. The reverse relationship was also explored. MR and meta-analysis identified significant associations between specific blood cell phenotypes and breast cancer: neutrophil perturbation response (side fluorescence standard deviation of neutrophil 4 in response to alhydrogel perturbation): odds ratio (OR) = 0.967, P = .0009; neutrophil perturbation response (forward scatter median of neutrophil 4 in response to Pam3CSK4 perturbation): OR = 0.972, P = .031; white blood cell perturbation response (side scatter coefficient of variation of WBC 2 in response to nigericin perturbation): OR = 0.972, P = .031; white blood cell perturbation response (forward scatter coefficient of variation of WBC in response to Pam3CSK4 perturbation): OR = 1.042, P = 8.15 × 10-5. And there was no reverse result. Neutrophil perturbation response (side fluorescence standard deviation of neutrophil 4 in response to alhydrogel perturbation) and white blood cell perturbation response (side scatter coefficient of variation of WBC 2 in response to nigericin perturbation) are protective factors for breast cancer. Conversely, neutrophil perturbation response (forward scatter median of neutrophil 4 in response to Pam3CSK4 perturbation) and white blood cell perturbation response (forward scatter coefficient of variation of WBC in response to Pam3CSK4 perturbation) are risk factors for breast cancer.