Munnik Floor, Gonçalves de Oliveira Kelin, Godina Christopher, Isaksson Karolin, Jernström Helena
Department of Clinical Sciences Lund, Oncology, Lund University Cancer Center/Kamprad, Skåne University Hospital, Lund University, Barngatan 4, 222 42 Lund, Sweden.
Division of Surgery, Department of Clinical Sciences in Lund, Lund University, 221 85 Lund, Sweden.
Cancers (Basel). 2025 Jul 17;17(14):2378. doi: 10.3390/cancers17142378.
Prolactin receptor (PRLR) signaling affects breastfeeding and potentially breast cancer treatment response. The prognostic impact of 20 single nucleotide polymorphisms (SNPs) in relation to adjuvant treatment groups in patients with primary breast cancer ( = 1701, 2002-2016, Sweden) was evaluated. Genomic DNA was genotyped on Illumina OncoArray, and survival analyses with up to 15-year follow-up were performed. Interaction models, adjusted for potential confounders, were created with different adjuvant treatment modalities: chemotherapy, radiotherapy, tamoxifen, and aromatase inhibitors. Five SNPs (rs7734558, rs6860397, rs2962101, rs7732013, and rs4703503) showed interactions with radiotherapy and were utilized to create seven combined genotypes: six unique and one 'rare'. Patients carrying combined genotype AG/GG/TT/CC/TC or 'rare' combinations derived greater benefits from radiotherapy than other patient groups (both HR ≤ 0.29, Bonferroni-adjusted ≤ 0.039). Expression Quantitative Trait Loci (eQTL) analysis revealed that three SNPs were associated with decreased expression. To explore potential SNP-associated effects, gene expression and transcriptional networks were analyzed in the METABRIC cohort and indicated that -low tumors were associated with reduced DNA repair signaling and enhanced anti-tumoral immunity. PRLR merits further evaluation as a putative pharmacogenomic biomarker in relation to radiotherapy for breast cancer patients.
催乳素受体（PRLR）信号传导影响母乳喂养以及潜在的乳腺癌治疗反应。评估了20个单核苷酸多态性（SNP）对原发性乳腺癌患者（n = 1701，2002 - 2016年，瑞典）辅助治疗组的预后影响。在Illumina OncoArray上对基因组DNA进行基因分型，并进行长达15年随访的生存分析。针对不同的辅助治疗方式（化疗、放疗、他莫昔芬和芳香化酶抑制剂）创建了调整潜在混杂因素的相互作用模型。五个SNP（rs7734558、rs6860397、rs2962101、rs7732013和rs4703503）显示与放疗存在相互作用，并用于创建七种组合基因型：六种独特的和一种“罕见的”。携带组合基因型AG/GG/TT/CC/TC或“罕见”组合的患者从放疗中获得的益处比其他患者组更大（HR均≤0.29，Bonferroni校正P≤0.039）。表达数量性状位点（eQTL）分析表明，三个SNP与表达降低相关。为了探索潜在的SNP相关效应，在METABRIC队列中分析了基因表达和转录网络，结果表明PRLR低表达的肿瘤与DNA修复信号降低和抗肿瘤免疫力增强有关。PRLR作为乳腺癌患者放疗的潜在药物基因组生物标志物值得进一步评估。
