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Genetic determinants and clinical significance of circulating and tumor-specific levels of insulin-like growth factor binding protein 7 (IGFBP7) in a Swedish breast cancer cohort

Godina, Christopher LU orcid ; Rosendahl, Ann H LU ; Gonçalves de Oliveira, Kelin LU ; Khazaei, Somayeh LU ; Björner, Sofie LU ; Jirström, Karin LU orcid ; Isaksson, Karolin LU ; Pollak, Michael N and Jernström, Helena LU (2025) In Carcinogenesis 46(2).
Abstract

Previous research indicates that insulin-like growth factor binding protein 7 (IGFBP7) protein levels in breast cancer tissue and blood are prognostic. However, genetic determinants of IGFBP7 in breast cancer remain largely unexplored. We examined IGFBP7 in a cohort of 1701 patients with a first breast cancer from Sweden, enrolled prior to surgery 2002-2016 and followed for up to 15 years. Genotyping was performed on blood samples using OncoArray. Tumor-specific protein levels of IGFBP7, insulin receptor (InsR), and IGF-I receptor (IGFIR) were assessed on tumor tissue microarrays in 964 patients. Further, 275 patients had plasma IGFBP7 levels measured. A genetic proxy marker for circulating IGFBP7 levels was constructed from five... (More)

Previous research indicates that insulin-like growth factor binding protein 7 (IGFBP7) protein levels in breast cancer tissue and blood are prognostic. However, genetic determinants of IGFBP7 in breast cancer remain largely unexplored. We examined IGFBP7 in a cohort of 1701 patients with a first breast cancer from Sweden, enrolled prior to surgery 2002-2016 and followed for up to 15 years. Genotyping was performed on blood samples using OncoArray. Tumor-specific protein levels of IGFBP7, insulin receptor (InsR), and IGF-I receptor (IGFIR) were assessed on tumor tissue microarrays in 964 patients. Further, 275 patients had plasma IGFBP7 levels measured. A genetic proxy marker for circulating IGFBP7 levels was constructed from five candidate single nucleotide polymorphisms (SNPs) (rs6852762, rs1714014, rs9992658, rs10004910, and rs4865180) based on number of recessive genotypes. Age-adjusted linear regression was used to evaluate SNPs and tumor-specific IGFBP7 levels in relation to circulating IGFBP7 levels. Cox regression adjusted for age, tumor characteristics, and adjuvant treatments was used to assess associations with clinical outcomes. Circulating and tumor-specific IGFBP7 levels were significantly positively correlated. High circulating and genetically predicted IGFBP7 levels were associated with increased risk for distant metastasis and all-cause mortality. A significant interaction between high tumor-specific IGFBP7 levels and membrane-bound InsR resulted in a four-fold increased risk of breast cancer events and distant metastases. Both measured and genetically predicted IGFBP7 levels were independent prognostic biomarkers in breast cancer.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Carcinogenesis
volume
46
issue
2
article number
bgaf020
publisher
Oxford University Press
external identifiers
  • scopus:105004997227
  • pmid:40230015
ISSN
0143-3334
DOI
10.1093/carcin/bgaf020
language
English
LU publication?
yes
additional info
© The Author(s) 2025. Published by Oxford University Press.
id
4eb81d90-3605-49f3-8a54-3b937d9e5ca7
date added to LUP
2025-04-16 08:12:29
date last changed
2025-07-23 07:07:48
@article{4eb81d90-3605-49f3-8a54-3b937d9e5ca7,
  abstract     = {{<p>Previous research indicates that insulin-like growth factor binding protein 7 (IGFBP7) protein levels in breast cancer tissue and blood are prognostic. However, genetic determinants of IGFBP7 in breast cancer remain largely unexplored. We examined IGFBP7 in a cohort of 1701 patients with a first breast cancer from Sweden, enrolled prior to surgery 2002-2016 and followed for up to 15 years. Genotyping was performed on blood samples using OncoArray. Tumor-specific protein levels of IGFBP7, insulin receptor (InsR), and IGF-I receptor (IGFIR) were assessed on tumor tissue microarrays in 964 patients. Further, 275 patients had plasma IGFBP7 levels measured. A genetic proxy marker for circulating IGFBP7 levels was constructed from five candidate single nucleotide polymorphisms (SNPs) (rs6852762, rs1714014, rs9992658, rs10004910, and rs4865180) based on number of recessive genotypes. Age-adjusted linear regression was used to evaluate SNPs and tumor-specific IGFBP7 levels in relation to circulating IGFBP7 levels. Cox regression adjusted for age, tumor characteristics, and adjuvant treatments was used to assess associations with clinical outcomes. Circulating and tumor-specific IGFBP7 levels were significantly positively correlated. High circulating and genetically predicted IGFBP7 levels were associated with increased risk for distant metastasis and all-cause mortality. A significant interaction between high tumor-specific IGFBP7 levels and membrane-bound InsR resulted in a four-fold increased risk of breast cancer events and distant metastases. Both measured and genetically predicted IGFBP7 levels were independent prognostic biomarkers in breast cancer.</p>}},
  author       = {{Godina, Christopher and Rosendahl, Ann H and Gonçalves de Oliveira, Kelin and Khazaei, Somayeh and Björner, Sofie and Jirström, Karin and Isaksson, Karolin and Pollak, Michael N and Jernström, Helena}},
  issn         = {{0143-3334}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{2}},
  publisher    = {{Oxford University Press}},
  series       = {{Carcinogenesis}},
  title        = {{Genetic determinants and clinical significance of circulating and tumor-specific levels of insulin-like growth factor binding protein 7 (IGFBP7) in a Swedish breast cancer cohort}},
  url          = {{http://dx.doi.org/10.1093/carcin/bgaf020}},
  doi          = {{10.1093/carcin/bgaf020}},
  volume       = {{46}},
  year         = {{2025}},
}