Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: Pooled individual data analysis of 17 prospective studies

the Nurses' Health Study Research Group

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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.

Original languageEnglish (US)
Pages (from-to)530-542
Number of pages13
JournalThe Lancet Oncology
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2010

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Insulin-Like Growth Factor Binding Protein 3
Somatomedins
Prospective Studies
Breast Neoplasms
Estrogen Receptors
Odds Ratio
Neoplasms
Hormones
Menarche
Menopause
Mitosis
Logistic Models
Alcohols
Apoptosis
Pregnancy

ASJC Scopus subject areas

  • Oncology

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Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk : Pooled individual data analysis of 17 prospective studies. / the Nurses' Health Study Research Group.

In: The Lancet Oncology, Vol. 11, No. 6, 01.06.2010, p. 530-542.

Research output: Contribution to journalArticle

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title = "Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: Pooled individual data analysis of 17 prospective studies",
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.",
author = "{the Nurses' Health Study Research Group} and Key, {Timothy J.} and Appleby, {Paul N.} and Reeves, {Gillian K.} and Roddam, {Andrew W.} and Helzlsouer, {K. J.} and Alberg, {A. J.} and Rollison, {D. E.} and K. Overvad and R. Kaaks and D. Trichopoulos and F. Clavel-Chapelon and P. Vineis and Chirlaque, {M. D.} and Peeters, {P. H.M.} and S. Rinaldi and E. Riboli and Allen, {N. E.} and Allen, {D. S.} and Fentiman, {I. S.} and Holly, {J. M.} and Vatten, {L. J.} and Holly, {J. M.} and D. Gunnell and S. Tretli and H. Gr{\o}nb{\ae}k and A. Tj{\o}nneland and K. Overvad and R. Krajcik and J. Manjer and P. Lenner and R. Kaaks and G. Hallmans and L. Baglietto and English, {D. R.} and Giles, {G. G.} and G. Severi and Morris, {H. A.} and Hankinson, {S. E.} and Schernhammer, {E. S.} and K. Koenig and A. Zeleniuch-Jacquotte and Arslan, {A. A.} and P. Toniolo and Shore, {R. E.} and V. Krogh and A. Micheli and F. Berrino and P. Muti and Rohan, {Thomas E.} and Howard Strickler",
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T1 - Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk

T2 - Pooled individual data analysis of 17 prospective studies

AU - the Nurses' Health Study Research Group

AU - Key, Timothy J.

AU - Appleby, Paul N.

AU - Reeves, Gillian K.

AU - Roddam, Andrew W.

AU - Helzlsouer, K. J.

AU - Alberg, A. J.

AU - Rollison, D. E.

AU - Overvad, K.

AU - Kaaks, R.

AU - Trichopoulos, D.

AU - Clavel-Chapelon, F.

AU - Vineis, P.

AU - Chirlaque, M. D.

AU - Peeters, P. H.M.

AU - Rinaldi, S.

AU - Riboli, E.

AU - Allen, N. E.

AU - Allen, D. S.

AU - Fentiman, I. S.

AU - Holly, J. M.

AU - Vatten, L. J.

AU - Holly, J. M.

AU - Gunnell, D.

AU - Tretli, S.

AU - Grønbæk, H.

AU - Tjønneland, A.

AU - Overvad, K.

AU - Krajcik, R.

AU - Manjer, J.

AU - Lenner, P.

AU - Kaaks, R.

AU - Hallmans, G.

AU - Baglietto, L.

AU - English, D. R.

AU - Giles, G. G.

AU - Severi, G.

AU - Morris, H. A.

AU - Hankinson, S. E.

AU - Schernhammer, E. S.

AU - Koenig, K.

AU - Zeleniuch-Jacquotte, A.

AU - Arslan, A. A.

AU - Toniolo, P.

AU - Shore, R. E.

AU - Krogh, V.

AU - Micheli, A.

AU - Berrino, F.

AU - Muti, P.

AU - Rohan, Thomas E.

AU - Strickler, Howard

PY - 2010/6/1

Y1 - 2010/6/1

N2 - 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.

AB - 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.

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