scholarly journals Insulin-like growth factor (IGF)-I, IGF binding protein-3, and breast cancer risk: eight years on

2006 ◽  
Vol 13 (2) ◽  
pp. 273-278 ◽  
Author(s):  
Andrew G Renehan ◽  
Michelle Harvie ◽  
Anthony Howell
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Binding Protein ◽  
Meta Analysis ◽  
Regulatory Peptides ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Igfbp 3

Insulin-like growth factor (IGF)-I, and its main binding protein, IGFBP-3, are multi-functional regulatory peptides of cell growth and survival, attributes important for tumourigenesis. Following seminal work published in 1998, it has been hypothesised that circulating concentrations of these growth factors may be associated with cancer risk. Systematic reviews have reported that high normal range circulating levels of total IGF-I predict for pre- but not post-menopausal breast cancer. By contrast, associations with circulating IGFBP-3 have been inconsistent. A cumulative meta-analysis demonstrates that earlier reported positive associations between IGFBP-3 and pre-menopausal breast cancer risk now seem less clear as large-size cohorts are published. The reasons are complex and include differences in study design, lack of standardisation between assays, and variations in IGFBP-3 proteolytic activity – these are discussed in this commentary.

scholarly journals IGF-I; IGF-binding protein-3 and breast cancer risk

2005 ◽  
Vol 8 (1) ◽  
Author(s):  
A. G. Renehan ◽  
M. Zwahlen ◽  
M. Egger ◽  
S. M. Shalet
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Binding Protein ◽  
Regulatory Peptides ◽  
Cancer Risk Assessment ◽  
Conventional View ◽  
Increased Risk ◽  
Igf I ◽  
Igfbp 3

Insulin-like growth factor I (IGF-I) and its main binding protein 3 (IGFBP-3) are multi-regulatory peptides important in tumour cell growth and survival. In the circulation, they occur in large quantities and are readily measured. Across a population, concentrations vary and this may impact on risk of cancers common in western societies. Emerging epidemiological evidence supports the notion that higher levels of IGF-I are associated with increased risk of pre-menopausal, but not post-menopausal, breast cancer. Higher levels of IGFBP-3 may also predict for increased risk of pre-menopausal breast cancer, but this is contrary to the conventional view that this peptide is tumour protective. Nutritional and lifestyle factors, important in breast cancer risk, also inter-relate with circulating levels of IGF-I, but in many circumstances, the relationships are complex. It is becoming increasingly important that the clinical breast oncologist understands the physiology of the IGF system and its potential role in cancer risk assessment and prevention.

scholarly journals Insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3) and breast cancer risk: observational and Mendelian randomization analyses

2019 ◽  
Author(s):  
Neil Murphy ◽  
Anika Knuppel ◽  
Nikos Papadimitriou ◽  
Richard M Martin ◽  
Konstantinos K Tsilidis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
World Health ◽  
International Agency ◽  
Insulin Like Growth Factor ◽  
Health Organization ◽  
The Uk ◽  
Igfbp 3

AbstractBackgroundEpidemiological evidence supports a positive association between circulating insulin-like growth factor-1 (IGF-1) concentrations and breast cancer risk, but both the magnitude and causality of this relationship are uncertain. We conducted observational analyses with adjustment for regression dilution bias, and Mendelian randomization (MR) analyses to allow causal inference.Patients and methodsWe investigated the associations between circulating IGF-1 concentrations and incident breast cancer risk in 206,263 women in the UK Biobank. Multivariable hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. HRs were corrected for regression dilution using repeat IGF-1 measures available in a subsample of 6,711 women. For the MR analyses, genetic variants associated with circulating IGF-1 and IGFBP-3 levels were identified and their association with breast cancer was examined with two-sample MR methods using genome-wide data from 122,977 cases and 105,974 controls.ResultsIn the UK Biobank, after a median follow-up of 7.1 years, 4,360 incident breast cancer cases occurred. In the multivariable-adjusted models corrected for regression dilution, higher IGF-1 concentrations were associated with a greater risk of breast cancer (HR per 5 nmol/L increment of IGF-1=1.11, 95%CI=1.07-1.16). Similar positive associations were found by follow-up time, menopausal status, body mass index, and other risk factors. In the MR analyses, a 5 nmol/L increment in genetically-predicted IGF-1 concentration was associated with greater breast cancer risk (odds ratio [OR]=1.05, 95%CI=1.01-1.10; Pvalue=0.02), with a similar effect estimate for estrogen positive (ER+) tumors, but no effect found for estrogen negative (ER-) tumors. Genetically-predicted IGFBP-3 concentrations were not associated with breast cancer risk (OR per 1-SD increment=1.00, 95%CI=0.97-1.04; Pvalue=0.98).ConclusionOur results support a probable causal relationship between circulating IGF-1 concentrations and breast cancer, suggesting that interventions targeting the IGF pathway may be beneficial in preventing breast tumorigenesis.DisclaimerWhere authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.

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