Correct.
Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis.
BACKGROUND: Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate cell growth and survival, and are thought to be important in tumour development. Circulating concentrations of IGF-I might be associated with an increased risk of cancer, whereas IGFBP-3 concentrations could be associated with a decreased cancer risk. METHODS: We did a systematic review and meta-regression analysis of case-control studies, including studies nested in cohorts, of the association between concentrations of IGF-I and IGFBP-3 and prostate, colorectal, premenopausal and postmenopausal breast, and lung cancer. Study-specific dose-response slopes were obtained by relating the natural log of odds ratios for different exposure levels to blood concentrations normalised to a percentile scale. FINDINGS: We identified 21 eligible studies (26 datasets), which included 3609 cases and 7137 controls. High concentrations of IGF-I were associated with an increased risk of prostate cancer (odds ratio comparing 75th with 25th percentile 1.49, 95% CI 1.14-1.95) and premenopausal breast cancer (1.65, 1.26-2.08) and high concentrations of IGFBP-3 were associated with increased risk of premenopausal breast cancer (1.51, 1.01-2.27). Associations were larger in assessments of plasma samples than in serum samples, and in standard case-control studies compared with nested studies. INTERPRETATION: Circulating concentrations of IGF-I and IGFBP-3 are associated with an increased risk of common cancers, but associations are modest and vary between sites. Although laboratory methods need to be standardised, these epidemiological observations could have major implications for assessment of risk and prevention of cancer.
Herlees het ff dr. P
Insulin-like growth factor (IGF)-I, IGF binding protein-3, and breast cancer risk: eight years on
ABSTRACT
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.
LAST PART OF ARTICLE
To summarise, the literature to-date indicates that there are no discernible associations between IGF-I, IGFBP-3 and post-menopausal breast cancer risk, that there are modest associations between IGF-I and breast cancer risk in pre-menopausal and young women, and that the main area of controversy is the relationship between IGFBP-3 and pre-menopausal breast cancer risk. To tackle this ‘muddy water’, there is a compelling need to standardise studies for comparative purposes. First is the problem of study design. The majority of cohort studies to-date determined associations between IGF analytes and breast cancer risk sub-classified into pre- and post-menopausal status at the time of diagnosis, rather than status at blood donation. At least for circulating IGFs and breast cancer risk, this distinction appears to be important and should be based on conventional medical record-based definitions of menopause rather than cut-offs by age group. It is a completely different scenario to design an analysis based on age at recruitment as was reported by Kaaks et al.(2002). Having stated this, it is still an interesting question to ask whether or not there is a relationship between pre-menopausal status at the time of collection of blood and subsequent post-menopausal breast cancer risk. This was specifically addressed by Rollison et al.(2006) who reported that higher levels of IGF-I in younger women (25 to 35 years) at recruitment might predict for subsequent post-menopausal breast cancer, whilst associations with IGFBP-3 were marginally inverse. As sub-group sizes were small, this study needs to be repeated with larger numbers.
The second problem is standardisation of the assays used, and here the debate focuses on IGFBP-3. Under normal conditions, there is an appreciable but variable level of IGFBP-3 serum proteolysis, which, in turn, may impact on the determination of ‘total’ IGFBP-3 concentrations in the circulation. Schernhammer et al.(2006) state that the radioimmunoassay is the ‘gold standard’, but this has not been robustly tested in the models of association of cancer risk.
The third problem is that of mutual adjustment of IGF-I and IGFBP-3 within multilevel analyses. Unquestionably, both analytes are well correlated and partly inter-dependent, but the statistical process of mutual adjustment is confusing. In some instances, there are potentiating associations (Hankinson et al. 1998, Allen et al. 2005); in others, attenuating associations (Krajcik et al. 2002, Rinaldi et al. 2006). In addition, reporting models of association based on the IGF-I/IGFBP-3 ratio is misleading as it may be confused with, and is a poor surrogate of, IGF-I bioavailability (Renehan et al. 2006). It seems prudent to report multilevel analyses with and without mutual adjustments in future studies.
Eight years on, the initial excitement about the determination of IGF analytes and the prediction of cancer risk may seem dampened. However, IGF analytes may still be useful markers of response to interventions (Harvie & Howell 2006), as they are inexpensive, well tested, and robust to variations in blood handling. In an era when peptide biochemists are focused on serum proteomics and metabolomics as predictors of disease, these new technologies are expensive to develop and troubled by reproducibility. Several dietary, lifestyle and pharmacological approaches may favourably modulate IGF physiology, offering untapped opportunities to prevent or modify disease progression in breast cancer and other common adult cancers.
ik neem aan dat hij mij bedoelde 
Toen hadden ze nog natuurlijke selectie enzo, en zou ik er ook niet geweest zijn....
Zelfs als ik niet zo snugger overkom zal dat nog niet automatisch betekenen dat de natuurlijke selectie mij verwijderd zou hebben...maar er is bijvoorbeeld iemand in mijn voorgeslacht die alleen dankzij de injecteerbare insuline oud genoeg heeft mogen worden om kinderen te verwekken. Maar ja de kans op zo iets is wel groot tegenwoordig...mag ik ervan uitgaan dat jij er ook niet geweest zou zijn ? 
