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.

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 Circulating concentrations of micro-nutrients and risk of breast cancer: A Mendelian randomization study

2019 ◽  
Author(s):  
N. Papadimitriou ◽  
N. Dimou ◽  
D. Gill ◽  
I. Tzoulaki ◽  
N. Murphy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mendelian Randomization ◽  
World Health ◽  
Sensitivity Analyses ◽  
International Agency ◽  
Inverse Association ◽  
Health Organization ◽  
Genetically Determined

AbstractBackgroundThe epidemiological literature reports inconsistent associations between consumption or circulating concentrations of micro-nutrients and breast cancer risk. We investigated associations between genetically determined concentrations of 11 micro-nutrients (beta-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6, vitamin B12 and zinc) and breast cancer risk using Mendelian randomization (MR).Materials and methodsA two-sample MR study was conducted using 122,977 women with breast cancer, of whom 69,501 were estrogen receptor positive (ER+ve) and 21,468 were ER−ve, and 105,974 controls from the Breast Cancer Association Consortium. MR analyses were conducted using the inverse variance weighted approach, and sensitivity analyses were conducted to assess the impact of potential violations of MR assumptions.ResultsOne standard deviation (SD: 0.08 mmol/L) higher genetically determined concentration of magnesium was associated with a 17% (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.10 to 1.25, P=9.1 × 10−7) and 20% (OR: 1.20, 95% CI: 1.11 to 1.30, P=3.17 × 10−6) higher risk of overall and ER+ve breast cancer, respectively. An inverse association was observed for a SD (0.5 mg/dL) higher genetically determined phosphorus concentration and ER−ve breast cancer (OR: 0.84, 95% CI: 0.72 to 0.98, P=0.03). A suggestive inverse association was observed for a SD (0.48 mg/dL) higher genetically determined calcium concentration with overall breast cancer (OR: 0.91, 95% CI: 0.83 to 1.00, P=0.06). There was little evidence that any of the other nutrients were associated with breast cancer. The results for magnesium were robust under all sensitivity analyses.ConclusionsHigher circulating concentrations of magnesium, phosphorus and calcium may affect breast cancer risk. Further work is required to replicate these findings and investigate underlying mechanisms.key messageWe conducted a Mendelian randomization study to investigate whether concentrations of 11 micro-nutrients are associated with risk of breast cancer. An increased risk of overall and oestrogen-receptor positive disease was observed for genetically higher concentrations of magnesium and inverse associations were observed for phosphorus and calcium concentrationsWhere 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.

scholarly journals Insulin-like Growth Factor 1 gene polymorphism and breast cancer risk

2016 ◽  
Vol 88 (4) ◽  
pp. 2349-2356 ◽  
Author(s):  
DANYLO R. COSTA-SILVA ◽  
MARIA DA CONCEIÇÃO BARROS-OLIVEIRA ◽  
RAFAEL S. BORGES ◽  
CLÉCITON B. TAVARES ◽  
UMBELINA S. BORGES ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Gene Polymorphism ◽  
Insulin Like Growth Factor

Reports: Insulin-Like Growth Factor-I, Soy Protein Intake, and Breast Cancer Risk

2004 ◽  
Vol 50 (1) ◽  
pp. 8-15 ◽  
Author(s):  
Maureen Sanderson ◽  
Xiao Ou Shu ◽  
Herbert Yu ◽  
Qi Dai ◽  
Alecia S. Malin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Soy Protein ◽  
Protein Intake ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I
Sign in / Sign up

Export Citation Format

Share Document