肿瘤免疫微环境（TIME）在肿瘤进展和免疫治疗反应中发挥着关键作用。先前的研究已经确定了与时间差异相关的个体种系变异。在这里，我们假设与乳腺癌风险或癌症相关特征相关的常见变异（以多基因风险评分（PRS）为代表）可能共同影响 TIME 中的免疫特征。我们从护士健康研究 (NHS) 和 NHSII 中 825 名乳腺癌患者的 764 个乳腺肿瘤和 598 个邻近正常组织样本的大量基因表达谱中得出了 154 个免疫特征。对 205 名个体的子集进行了四种免疫细胞标记物的免疫组织化学染色。计算了 16 种不同特征的种系 PRS，包括乳腺癌、自身免疫性疾病、2 型糖尿病、初潮和绝经年龄、体重指数 (BMI)、BMI 调整的腰臀比、饮酒量和吸烟情况。总体而言，我们以错误发现率 q < 0.25 确定了种系 PRS 与免疫特征之间的 44 个关联，其中包括 3 个 q < 0.05 的关联。我们观察到炎症性肠病 (IBD) 和克罗恩病 (CD) PRS 与乳腺肿瘤和邻近正常组织中的干扰素信号传导和 STAT1 评分存在一致的负相关关系；这些关联在挪威队列中得到了复制。正常组织中 IBD PRS 和 B 细胞丰度也一致观察到负相关。我们还观察到 CD PRS 与肿瘤中内皮细胞丰度之间存在正相关。我们的研究结果表明，影响免疫相关疾病的遗传机制也与乳腺癌中的 TIME 有关。由 Elsevier Inc. 出版。

The tumor immune microenvironment (TIME) plays key roles in tumor progression and response to immunotherapy. Previous studies have identified individual germline variants associated with differences in TIME. Here, we hypothesize that common variants associated with breast cancer risk or cancer-related traits, represented by polygenic risk scores (PRSs), may jointly influence immune features in TIME. We derived 154 immune traits from bulk gene expression profiles of 764 breast tumors and 598 adjacent normal tissue samples from 825 individuals with breast cancer in the Nurses' Health Study (NHS) and NHSII. Immunohistochemical staining of four immune cell markers were available for a subset of 205 individuals. Germline PRSs were calculated for 16 different traits including breast cancer, autoimmune diseases, type 2 diabetes, ages at menarche and menopause, body mass index (BMI), BMI-adjusted waist-to-hip ratio, alcohol intake, and tobacco smoking. Overall, we identified 44 associations between germline PRSs and immune traits at false discovery rate q < 0.25, including 3 associations with q < 0.05. We observed consistent inverse associations of inflammatory bowel disease (IBD) and Crohn disease (CD) PRSs with interferon signaling and STAT1 scores in breast tumor and adjacent normal tissue; these associations were replicated in a Norwegian cohort. Inverse associations were also consistently observed for IBD PRS and B cell abundance in normal tissue. We also observed positive associations between CD PRS and endothelial cell abundance in tumor. Our findings suggest that the genetic mechanisms that influence immune-related diseases are also associated with TIME in breast cancer.Published by Elsevier Inc.