摘要:SummaryProper immune system function hinders cancer development, but little is known about whether genetic variants linked to cancer risk alter immune cells. Here, we report 57 cancer risk loci associated with differences in immune and/or stromal cell contents in the corresponding tissue. Predicted target genes show expression and regulatory associations with immune features. Polygenic risk scores also reveal associations with immune and/or stromal cell contents, and breast cancer scores show consistent results in normal and tumor tissue.SH2B3links peripheral alterations of several immune cell types to the risk of this malignancy. PleiotropicSH2B3variants are associated with breast cancer risk inBRCA1/2mutation carriers. A retrospective case-cohort study indicates a positive association between blood counts of basophils, leukocytes, and monocytes and age at breast cancer diagnosis. These findings broaden our knowledge of the role of the immune system in cancer and highlight promising prevention strategies for individuals at high risk.Graphical AbstractDisplay OmittedHighlights•Cancer risk genetic variants linked to immune/stromal cell tissue content•SH2B3associated with BRCA1/2 cancer risk and immune cell counts•Peripheral immune cell types linked to breast cancer age at diagnosisImmunology; Cancer Systems Biology; Cancer