IGF‐I and breast cancer: A meta‐analysis

Abstract

IGFs are peptide hormones involved in the regulation of cell proliferation, differentiation and apoptosis. IGFs are regulated by endocrine and paracrine mechanisms; however, their action in tissue is determined by circulating levels and local production of IGFs and IGF-binding proteins (IGFBPs). Some, but not all, epidemiologic studies have associated high circulating levels of IGF-I with increased risk of breast cancer among premenopausal women. To evaluate the overall association of IGF-I and IGFBP-3 levels with breast cancer risk, we performed a meta-analysis on 16 publications of epidemiologic and clinical studies. Analyses were performed for all women as well as for pre-and postmenopausal women separately. Hedges' standardized mean differences (HSMDs) and odds ratios (ORs) were used to estimate the effect of IGF-I and IGFBP-3. Data analysis showed that circulating levels of IGF-I were not significantly higher in breast cancer patients than in controls for all women and for the postmeno- Key words: IGF-I; breast cancer; meta-analysis; case-control studyIGFs are peptide hormones involved in the regulation of cell proliferation, differentiation and apoptosis. They are regulated by both endocrine and paracrine mechanisms. Most IGFs in the circulation originate from the liver. However, their action in tissue is determined not only by circulating levels of IGFs and IGF-binding proteins (IGFBPs) but also by local production of the molecules. 1 There is large interpersonal variability in circulating concentrations of IGF-I and IGFBP-3. 2,3 Higher serum levels of IGF-I have been associated with increased risk of prostate cancer 4,5 as well as other malignancies. 6 Several epidemiologic studies 7-11 and reviews 6,12 have also suggested that elevated IGF-I may play a role in breast cancer risk. A positive association between circulating levels of IGF-I and risk of breast cancer was found among premenopausal, but not postmenopausal, women in prospective cohort studies. 10 Although the mechanism underlying the association between IGF level and breast cancer remains to be elucidated, it is speculated that IGFs, including IGF-I and the main binding protein IGFBP-3, may play an important role in the pathogenesis of breast cancer. 7,8,10,13 The level of IGF is negatively associated with age. 7,10 IGF-I levels are lower in postmenopausal women than premenopausal women. 8,14 Some studies have reported that IGF-I levels were higher in breast cancer patients than in control subjects, 7,8,11,[15][16][17] whereas others have shown the opposite association. 10,14,18 -20 IGF-I levels vary among both premenopausal and postmenopausal women. One of 8 studies in premenopausal 19 and 3 of 7 studies in postmenopausal 11,19,21 women have shown higher serum IGF-I levels in cases than in controls. Several studies have shown that breast cancer patients have higher serum IGFBP-3 levels than controls, 11,14,16,22,23 but one study has found the opposite association. 15 To further examine the association of IGF-I with breast cancer, we performe...

Phenotypes and genotypes of insulin-like growth factor 1, IGF-binding protein-3 and cancer risk: evidence from 96 studies

“…3,4 From the present pooled analyses, we found that higher concentrations of IGF1 were significantly associated with an increased risk of pre-menopausal breast cancer but not of post-menopausal breast cancer, which was consistent with previously published studies. 4,39,40 It was reported that estrogen could interact with IGF1 to increase cell proliferation, particularly in breast cancer cells. 41 In addition, both estrogen 42 and IGF1 levels were higher in pre-menopausal breast cancer than those in post-menopausal breast cancer, suggesting that IGF1 might have a different role in pre-and postmenopausal breast cancers.…”

IGF‐I, IGF binding protein‐3 and breast cancer risk: Comparison of 3 meta‐analyses

“…2,3 At first glance, there are some differences in the results and the derived conclusions. This correspondence addresses the reasons.…”

“…Moreover, this approach failed to calculate estimates for associations with IGFBP-3 in several studies despite ORs and 95% CIs being reported for these individual studies, e.g., the study by Muti et al 6 Additionally, this approach did not allow the opportunity to compare pooled estimates calculated from maximally adjusted ORs with those calculated from minimally adjusted ORs, as we had performed within our sensitivity analyses (webappendix7 www.christie.man.ac.uk/profinfo/ departments/surgery/default.htm). Despite these differences (and potential limitations), the findings of these 2 reviews are broadly similar-concentrations of both total IGF-I and IGFBP-3 are positively associated with premenopausal breast cancer risk-though the method used by Shi et al 2 tended to give more conservative estimates of these effects.…”

“…The review of Shi et al 2 used less restrictive inclusion criteria and included 16 publications. The meta-analysis was performed using a method known as Hedges' standardised mean differences, involving calculation of weighted mean effect sizes and their 95% CIs from the reported concentrations of each peptide for each individual study.…”

IGFBP1 and IGFBP3 polymorphisms predict circulating IGFBP-3 levels among women from high-risk breast cancer families

“…In some studies, genetic variants and IGFBP-3 levels were inversely associated with breast cancer risk [21,22], while in other studies, IGFBP-3 levels were positively associated with breast cancer risk [7,23]. In addition, meta-analyses report that high circulating IGFBP-3 levels were associated with increased risk of premenopausal breast cancer [24,25].…”