Insulin‐like growth factor (IGF)‐I and IGF‐binding protein 3 and the risk of premenopausal breast cancer: A meta‐analysis of literature

Sugumar, Aravind; Liu, Yen-Chun; Xia, Qiang; Koh, Yea-Suk; Matsuo, Keitaro

doi:10.1002/ijc.20253

Cited by 79 publications

(68 citation statements)

References 26 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2009

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Insulin-like growth factor 1 (IGF1) and its main binding protein, IGF-binding protein 3 (IGFBP3), play an important role in cancer development. Circulating levels and functional polymorphisms of IGF1 and IGFBP3 may be biomarkers of cancer development. However, the results of published studies remain conflicting rather than conclusive. We searched MEDLINE and EMBASE databases for all published studies related to circulating levels and polymorphisms of IGF1 and IGFBP3 and cancer risk. In all, 96 studies and over 110 000 subjects were available for this meta-analysis. Higher IGF1 circulating levels significantly increased 15% of cancer risk (odds ratio (OR), 1.15, 95% confidence interval (CI), 1.03-1.29), especially among prostate, pre-menopausal breast and colorectal cancer patients, whereas higher concentrations of IGFBP3 significantly decreased the risk of advanced prostate cancer by 56% (OR, 0.44, 95% CI, 0.25 -0.77). Meanwhile, IGFBP3 À202CC genotype was associated with an increased risk of prostate cancer with borderline significance (OR, 1.18, 95% CI, 0.99 -1.41). Genotype-phenotype correlation analyses showed that circulating levels of IGFBP3 could be modified by its promoter polymorphism AÀ202C (P o 0.001). In conclusion, circulating levels of IGF1, IGFBP3 and IGFBP3 AÀ202C play a crucial role in carcinogenesis and could serve as susceptibility biomarkers for cancer development.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2009

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“…The authors performed their meta-analysis based on 6 studies and concluded that there were marginally significant associations with IGF-I concentrations but no associations with IGFBP-3 concentrations. We repeated these analyses and discovered that there were major discrepancies between the 95% CIs listed by Sugumar et al 3 and those stated within the individual studies (Table I). Specifically, the 95% CIs used in Table II and the forest plots of their report were considerably wider than those reported by the original studies, probably reflecting a miscalculation during log transformation.…”

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confidence: 92%

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

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confidence: 96%

“…The meta-analysis reported by Sugumar et al 3 was limited to premenopausal breast cancer and used similar selection criteria to those in our review. One major difference was the inclusion of a study of associations between the IGF peptides and breast ductal carcinoma in situ, 7 whereas only studies in which the end point was invasive cancer were included in our analysis.…”

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confidence: 99%

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

Renehan

Egger

Minder

et al. 2005

Intl Journal of Cancer

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Dear Sir,Earlier this year, we reported the results of a systematic review and meta-regression analysis determining the relationships between circulating total IGF-I and IGF binding protein-3 (IGFBP-3) concentrations and common cancer risk, including premenopausal and postmenopausal breast cancers. 1Two subsequent meta-analyses have been published specifically examining relationships with breast cancer risk.2,3 At first glance, there are some differences in the results and the derived conclusions. This correspondence addresses the reasons.Our study determined associations between circulating IGF peptides and cancer risk at 4 sites: prostate, colorectum, breast (considered pre-and postmenopausal) and lung. Strict inclusion criteria were used, namely, that findings were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Statistical analyses were performed at 2 levels: (i) a baseline metaanalysis of ORs comparing the highest and lowest (referent) category for each cancer site using conventional randomeffects methods 4 and (ii) a meta-regression analysis of the study-specific dose-response slopes generated using the method described by Greenland and Longnecker. 5 For breast cancer, the results from the 2 analyses were similar and demonstrated that higher concentrations of both IGF-I and IGFBP-3 were significantly positively associated with increased risk of premenopausal, but not postmenopausal, breast cancer. Furthermore, through sensitivity analyses, we demonstrated that the associations with IGF-I and IGFBP-3 were likely to be independent of each other (webappendix8 www.christie.man. ac.uk/profinfo/departments/surgery/default.htm). The positive association between higher circulating IGF-I and premenopausal breast cancer is not unexpected as IGF-I is mitogenic, antiapoptotic and proangiogenic, attributes that favour tumour development. However, the observation that circulating IGFBP-3 levels are positively associated with premenopausal breast cancer risk is contrary to perceived convention, which suggests that inverse associations should prevail as IGFBP-3 is predominantly antitumour in laboratory experiments and consequently the subject of debate (www.christie.man.ac.uk/ profinfo/departments/surgery/default.htm).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. From this and knowing the number of cases and controls, a correlation coefficient was calculated, with ORs and their 95% CIs estimated. While this approach allowed the meta-analysis to capture more studies for associations with IGF-I, the estimated ORs and 95% CIs differed for most studies from those reported originally. Moreover, this approach failed to calculate estimates for associations with IGFBP-3 in several studies despite ORs and 95% CIs being repor...

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“…These analyses also took into account potential effects of hyperinsulinemia, by including insulin and leptin, which we show to have no independent associations with breast cancer of their own accord. Serum IGF-I appears to be associated with risk of breast cancer among premenopausal women (7,10,12,13,15,17,24,25), but no similar association has been found among postmenopausal women (10,26). Several explanations for this dichotomy have been proposed.…”

Section: Discussionmentioning

confidence: 99%

Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer

Pazaitou‐Panayiotou¹,

Kelesidis²,

Kelesidis³

et al. 2007

eur j endocrinol

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Objective: Several components of the GH and IGF systems have been implicated in the development of malignancies. All components of these hormonal systems have never been jointly evaluated in female breast cancer, and previous studies have not examined the role of IGF-binding proteins (IGFBP-4, IGFBP-6) or GH-binding protein (GHBP). Design: Hospital-based case-control study. Methods: In this sample of primarily postmenopausal women, we obtained serum measures of IGF-I, IGF-II, and binding proteins IGFBP-1, IGFBP-3, IGFBP-4, IGFBP-6, as well as GHBP, insulin, and leptin from 74 breast cancer cases and 76 control subjects. Results: In crude analyses, we found lower age-standardized mean IGF-I, IGFBP-3, IGFBP-4, IGFBP-6, and higher IGFBP-1 and GHBP in breast cancer cases when compared with controls. Multivariate models mutually adjusted for other GH-IGF system components and classical breast cancer risk factors demonstrated an inverse association between IGFBP-3 and risk of breast cancer (odds ratio (OR)Z0.2, P!0.01) and a direct association between GHBP and disease risk (ORZ3.3, P!0.01). No significant associations were detected in multivariate analyses among IGF-I, IGF-II or IGFBP-1, IGFBP-4, IGFBP-6 with risk of breast cancer, indicating that these factors may not have effects independent of and/or comparable with IGFBP-3 and GHBP. Conclusions: These results support a protective role of IGFBP-3 and demonstrate for the first time an increased risk of breast cancer with higher GHBP, after accounting for variation in IGFs, IGFBPs, and classical breast cancer risk factors.

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Insulin‐like growth factor (IGF)‐I and IGF‐binding protein 3 and the risk of premenopausal breast cancer: A meta‐analysis of literature

Cited by 79 publications

References 26 publications

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

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

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

Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer

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