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Meta-Analysis

Insulin-like Growth Factor 1 (IGF1), IGF Binding Protein 3 (IGFBP3), and Breast Cancer Risk: Pooled Individual Data Analysis of 17 Prospective Studies

Endogenous Hormones and Breast Cancer Collaborative Group et al. Lancet Oncol.

Abstract

Background: Insulin-like growth factor 1 (IGF1) stimulates mitosis and inhibits apoptosis. Some published results have shown an association between circulating IGF1 and breast-cancer risk, but it has been unclear whether this relationship is consistent or whether it is modified by IGF binding protein 3 (IGFBP3), menopausal status, oestrogen receptor status or other factors. The relationship of IGF1 (and IGFBP3) with breast-cancer risk factors is also unclear. The Endogenous Hormones and Breast Cancer Collaborative Group was established to analyse pooled individual data from prospective studies to increase the precision of the estimated associations of endogenous hormones with breast-cancer risk.

Methods: Individual data on prediagnostic IGF1 and IGFBP3 concentrations were obtained from 17 prospective studies in 12 countries. The associations of IGF1 with risk factors for breast cancer in controls were examined by calculating geometric mean concentrations in categories of these factors. The odds ratios (ORs) with 95% CIs of breast cancer associated with increasing IGF1 concentrations were estimated by conditional logistic regression in 4790 cases and 9428 matched controls, with stratification by study, age at baseline, and date of baseline. All statistical tests were two-sided, and a p value of less than 0.05 was considered significant.

Findings: IGF1 concentrations, adjusted for age, were positively associated with height and age at first pregnancy, inversely associated with age at menarche and years since menopause, and were higher in moderately overweight women and moderate alcohol consumers than in other women. The OR for breast cancer for women in the highest versus the lowest fifth of IGF1 concentration was 1.28 (95% CI 1.14-1.44; p<0.0001). This association was not altered by adjusting for IGFBP3, and did not vary significantly by menopausal status at blood collection. The ORs for a difference in IGF1 concentration between the highest and lowest fifth were 1.38 (95% CI 1.14-1.68) for oestrogen-receptor-positive tumours and 0.80 (0.57-1.13) for oestrogen-receptor-negative tumours (p for heterogeneity=0.007).

Interpretation: Circulating IGF1 is positively associated with breast-cancer risk. The association is not substantially modified by IGFBP3, and does not differ markedly by menopausal status, but seems to be confined to oestrogen-receptor-positive tumours.

Funding: Cancer Research UK.

Figures

Figure 1
Figure 1
Geometric mean IGF1 concentrations (nmol/L with 95% CI) among controls by selected factors Adjusted for study and age at blood collection, as appropriate. *Means are scaled to the overall geometric mean concentration. †p values for tests of heterogeneity and, where applicable and in parenthesis, linear trend. ‡Values are depicted as a proportion of the overall geometric mean concentration (dotted line). §p<0·05 for test of interaction with study.
Figure 2
Figure 2
Odds ratios (OR) for breast cancer associated with IGF1 and IGFBP3 among premenopausal women (at blood collection), postmenopausal women (at blood collection), and all women The black squares indicate the ORs and the horizontal lines show the 95% CIs. The area of each square is proportional to the amount of statistical information (inverse of the variance of the logarithm of the OR). Estimates are from conditional logistic regression on case-control sets matched within each study.
Figure 3
Figure 3
Odds ratios (OR) for breast cancer associated with IGF1 concentrations in women who were premenopausal at blood collection (A), and postmenopausal at blood collection (B) The OR is the estimate of the linear trend for IGF1 obtained by replacing the categorical variables representing the fifths of concentration in controls by a continuous variable scored as 0, 0·25, 0·5, 0·75, and 1. The black squares indicate the ORs and the horizontal lines show the 95% CIs. The area of each square is proportional to the amount of statistical information (inverse of the variance of the logarithm of the OR). The diamonds indicate the OR and 95% CI for all studies combined. Estimates are from conditional logistic regression on case-control sets matched within each study. EPIC=European Prospective Investigation into Cancer and Nutrition. KKH=Danish Diet, Cancer, and Health study. KP-OFAS=Kaiser Permanente-Orentreich Foundation Study. MCCS=Melbourne Collaborative Cohort Study. NYU WHS=New York University Women's Health Study. ORDET=Study of Hormones and Diet in the Etiology of Breast Tumours. PLCO=Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. PPHV=Monitoring Project on Cardiovascular Disease Risk Factors. SOF=Study of Osteoporotic Fractures. WHI-OS=Women's Health Initiative, Observational Study.
Figure 4
Figure 4
Odds ratios (OR) for breast cancer associated with IGF1 concentration, according to menopausal status at blood collection and other factors The OR is the estimate of the linear trend obtained by replacing the categorical variables representing the fifths of IGF1 concentration in controls by a continuous variable scored as 0, 0·25, 0·5, 0·75 and 1. Black squares indicate the OR and the horizontal lines show the 95% CIs. The area of each square is proportional to the amount of statistical information (inverse of the variance of the logarithm of the OR). The vertical dotted line indicates the OR for all studies. Tests for heterogeneity are for the difference in the association of IGF1 with breast-cancer risk between subgroups. Estimates are from conditional logistic regression on case-control sets matched within each study. HRT=Hormone replacement therapy.

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References

    1. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008;8:915–928. - PubMed
    1. Samani AA, Yakar S, LeRoith D, Brodt P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev. 2007;28:20–47. - PubMed
    1. Furlanetto RW, DiCarlo JN. Somatomedin-C receptors and growth effects in human breast cells maintained in long-term tissue culture. Cancer Res. 1984;44:2122–2128. - PubMed
    1. Pollak MN, Perdue JF, Margolese RG, Baer K, Richard M. Presence of somatomedin receptors on primary human breast and colon carcinomas. Cancer Lett. 1987;38:223–230. - PubMed
    1. Peyrat JP, Bonneterre J, Hecquet B. Plasma insulin-like growth factor-1 (IGF-1) concentrations in human breast cancer. Eur J Cancer. 1993;29A:492–497. - PubMed

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