Prognostic Differences of Adjuvant Radiotherapy in Breast Cancer Cohorts Based on PRLR Genotypes, Expression, and Transcriptional Network Regulation
(2025) In Cancers 17(14).- 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... (More)
- 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 HRadj ≤ 0.29, Bonferroni-adjusted Pint ≤ 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/b563aa32-af47-4fb2-9b8a-0084dfac2a07
- author
- Munnik, Floor
LU
; Gonçalves de Oliveira, Kelin
LU
; Godina, Christopher
LU
; Isaksson, Karolin LU and Jernström, Helena LU
- organization
- publishing date
- 2025-07-17
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cancers
- volume
- 17
- issue
- 14
- article number
- 2378
- publisher
- MDPI AG
- external identifiers
-
- pmid:40723262
- scopus:105011484384
- ISSN
- 2072-6694
- DOI
- 10.3390/cancers17142378
- language
- English
- LU publication?
- yes
- id
- b563aa32-af47-4fb2-9b8a-0084dfac2a07
- date added to LUP
- 2025-09-09 11:01:48
- date last changed
- 2025-09-10 04:06:00
@article{b563aa32-af47-4fb2-9b8a-0084dfac2a07, 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 HRadj ≤ 0.29, Bonferroni-adjusted Pint ≤ 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.}}, author = {{Munnik, Floor and Gonçalves de Oliveira, Kelin and Godina, Christopher and Isaksson, Karolin and Jernström, Helena}}, issn = {{2072-6694}}, language = {{eng}}, month = {{07}}, number = {{14}}, publisher = {{MDPI AG}}, series = {{Cancers}}, title = {{Prognostic Differences of Adjuvant Radiotherapy in Breast Cancer Cohorts Based on PRLR Genotypes, Expression, and Transcriptional Network Regulation}}, url = {{http://dx.doi.org/10.3390/cancers17142378}}, doi = {{10.3390/cancers17142378}}, volume = {{17}}, year = {{2025}}, }