Journal Article Epublish
PubMed: 40723262 DOI: 10.3390/cancers17142378
Prognostic Differences of Adjuvant Radiotherapy in Breast Cancer Cohorts Based on PRLR Genotypes, Expression, and Transcriptional Network Regulation.
Cancers (Basel) 17(14)
Authors: Floor Munnik, Kelin Gonçalves de Oliveira, Christopher Godina, Karolin Isaksson, Helena Jernström
Affiliations
- 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.
- Department of Surgery, Skåne University Hospital, 291 85 Kristianstad, Sweden.
Abstract
Background: Prolactin receptor (PRLR) signaling affects breastfeeding and potentially breast cancer treatment response. Methods: The prognostic impact of 20 PRLR single nucleotide polymorphisms (SNPs) in relation to adjuvant treatment groups in patients with primary breast cancer (n = 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. Results: 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 adj ≤ 0.29, Bonferroni-adjusted P int ≤ 0.039). Expression Quantitative Trait Loci (eQTL) analysis revealed that three PRLR SNPs were associated with decreased PRLR expression. To explore potential SNP-associated effects, gene expression and transcriptional networks were analyzed in the METABRIC cohort and indicated that PRLR-low tumors were associated with reduced DNA repair signaling and enhanced anti-tumoral immunity. Conclusions: PRLR merits further evaluation as a putative pharmacogenomic biomarker in relation to radiotherapy for breast cancer patients.
MeSH
Radiotherapy, Gene Regulatory Networks, Breast Neoplasms, Neoplasms, Radiotherapy, Adjuvant, Biomarkers, Breast, Genotype, Therapeutics, Polymorphism, Single Nucleotide, Prognosis