Proper 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. SH2B3 links peripheral alterations of several immune cell types to the risk of this malignancy. Pleiotropic SH2B3 variants are associated with breast cancer risk in BRCA1/2 mutation 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.

适当的免疫系统功能会阻碍癌症的发展，但与癌症风险相关的遗传变异是否会改变免疫细胞知之甚少。在此，我们报告了57个与相应组织中免疫和/或基质细胞含量差异相关的癌症风险基因座。预测的靶基因显示出表达和调节关联与免疫功能。多基因风险评分还揭示了与免疫和/或基质细胞含量的相关性，乳腺癌评分表明在正常和肿瘤组织中的结果一致。SH2B3将几种免疫细胞类型的外周改变与这种恶性肿瘤的风险联系起来。多发性SH2B3变异与BRCA1 / 2中的乳腺癌风险相关突变携带者。一项回顾性病例队列研究表明，在乳腺癌诊断中，嗜碱性粒细胞，白细胞和单核细胞的血细胞计数与年龄之间存在正相关。这些发现拓宽了我们对免疫系统在癌症中的作用的认识，并突出了针对高危人群的有希望的预防策略。