This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krajcik, R. A. Articles by Orentreich, N. Search for Related Content PubMed PubMed Citation Articles by Krajcik, R. A. Articles by Orentreich, N.

Insulin-like Growth Factor I (IGF-I), IGF-binding Proteins, and Breast Cancer

Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, New York 10516

Epidemiological evidence supports a role for the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) in the induction and progression of various cancers. Estrogen, which plays a role in the etiology of breast cancer, both regulates and is influenced by the IGF family. Risk of breast cancer associated with serum levels of IGF-I and/or IGFBPs may therefore depend upon menopausal status. A nested, case-control study was conducted on 66 women who were premenopausal and 60 who were postmenopausal at the time of diagnosis of primary breast cancer; they were selected from a cohort of 95,000 women who underwent multiphasic health check-ups > 30 years ago when enrolled in the Kaiser Permanente Medical Care Program. For each case, one control who matched by age, date of examination, and length of follow-up was chosen. Concentrations of IGF-I, insulin, glucose, and IGFBP-1, IGFBP-2, and IGFBP-3 in serum drawn at least 2 years before diagnosis (mean times of 10.5 and 15.8 years for pre- and postmenopausal cases, respectively) were compared using conditional logistic regression analysis. All statistical tests were two-sided. Serum IGF-I, adjusted for insulin, glucose, and body mass index, was weakly associated with breast cancer risk across quartiles for premenopausal women only (P for trend = 0.05). Serum IGFBP-3 was higher in premenopausal cases versus controls (P = 0.04) and showed a positive trend in risk for increasing quartiles (P for trend = 0.033). After adjusting for insulin, glucose, body mass index, and IGF-I, premenopausal women in the highest quartile of IGFBP-3 had an elevated risk of breast cancer [odds ratio (OR) = 5.28, 95% confidence interval (CI) = 1.13–24.7]. Conversely, IGFBP-3 was lower in postmenopausal cases versus controls (P = 0.04) but showed no significant trend in risk. Postmenopausal women with glucose levels in the diabetic range were at increased risk for developing breast cancer (OR = 2.06, 95% CI = 0.87–4.91), whereas those in the highest quartile of IGFBP-2 had a substantial reduction (71%) in risk relative to those in the lowest quartile (OR = 0.29, 95% CI = 0.09–0.92). Serum IGFBP-1 was not associated with breast cancer risk in either pre- or postmenopausal women. In premenopausal women, elevated serum IGF-I and IGFBP-3 are associated with increased breast cancer risk, whereas elevated serum IGFBP-2 is inversely associated with risk of postmenopausal breast cancer.

This article has been cited by other articles:

				S. H. Siahpush, T. L. Vaughan, J. N. Lampe, R. Freeman, S. Lewis, R. D. Odze, P. L. Blount, K. Ayub, P. S. Rabinovitch, B. J. Reid, et al. Longitudinal Study of Insulin-like Growth Factor, Insulin-like Growth Factor Binding Protein-3, and their Polymorphisms: Risk of Neoplastic Progression in Barrett's Esophagus Cancer Epidemiol. Biomarkers Prev., November 1, 2007; 16(11): 2387 - 2395. [Abstract] [Full Text] [PDF]

				E. S Schernhammer, S. S Tworoger, A H. Eliassen, S. A Missmer, J. M Holly, M. N Pollak, and S. E Hankinson Body shape throughout life and correlations with IGFs and GH Endocr. Relat. Cancer, September 1, 2007; 14(3): 721 - 732. [Abstract] [Full Text] [PDF]

				L. Baglietto, D. R. English, J. L. Hopper, H. A. Morris, W. D. Tilley, and G. G. Giles Circulating Insulin-Like Growth Factor-I and Binding Protein-3 and the Risk of Breast Cancer Cancer Epidemiol. Biomarkers Prev., April 1, 2007; 16(4): 763 - 768. [Abstract] [Full Text] [PDF]

				M. Verheus, P. H.M. Peeters, R. Kaaks, P. A.H. van Noord, D. E. Grobbee, and C. H. van Gils Premenopausal Insulin-Like Growth Factor-I Serum Levels and Changes in Breast Density over Menopause Cancer Epidemiol. Biomarkers Prev., March 1, 2007; 16(3): 451 - 457. [Abstract] [Full Text] [PDF]

				K. Pazaitou-Panayiotou, T. Kelesidis, I. Kelesidis, A. Kaprara, J. Blakeman, I. Vainas, A. Mpousoulegas, C. J Williams, and C. Mantzoros Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer Eur. J. Endocrinol., February 1, 2007; 156(2): 187 - 194. [Abstract] [Full Text] [PDF]

				C. D. Tran, C. Diorio, S. Berube, M. Pollak, and J. Brisson Relation of insulin-like growth factor (IGF) I and IGF-binding protein 3 concentrations with intakes of fruit, vegetables, and antioxidants Am. J. Clinical Nutrition, December 1, 2006; 84(6): 1518 - 1526. [Abstract] [Full Text] [PDF]

				R. M. Martin, J. M. P. Holly, G. Davey Smith, and D. Gunnell Associations of Adiposity from Childhood into Adulthood with Insulin Resistance and the Insulin-Like Growth Factor System: 65-Year Follow-Up of the Boyd Orr Cohort J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3287 - 3295. [Abstract] [Full Text] [PDF]

				Y. Lin, Q. Yang, X. Wang, and Z.-g. Liu The Essential Role of the Death Domain Kinase Receptor-interacting Protein in Insulin Growth Factor-I-induced c-Jun N-terminal Kinase Activation J. Biol. Chem., August 18, 2006; 281(33): 23525 - 23532. [Abstract] [Full Text] [PDF]

				M. Tseng, C. Byrne, K. A. Evers, W. T. London, and M. B. Daly Acculturation and breast density in foreign-born, u.s. Chinese women. Cancer Epidemiol. Biomarkers Prev., July 1, 2006; 15(7): 1301 - 1305. [Abstract] [Full Text] [PDF]

				A. G Renehan, M. Harvie, and A. Howell Insulin-like growth factor (IGF)-I, IGF binding protein-3, and breast cancer risk: eight years on. Endocr. Relat. Cancer, June 1, 2006; 13(2): 273 - 278. [Abstract] [Full Text] [PDF]

				E. S Schernhammer, J. M Holly, D. J Hunter, M. N Pollak, and S. E Hankinson Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth hormone and breast cancer risk in The Nurses Health Study II. Endocr. Relat. Cancer, June 1, 2006; 13(2): 583 - 592. [Abstract] [Full Text] [PDF]

				S Rinaldi, P H M Peeters, F Berrino, L Dossus, C Biessy, A Olsen, A Tjonneland, K Overvad, F Clavel-Chapelon, M C Boutron-Ruault, et al. IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr. Relat. Cancer, June 1, 2006; 13(2): 593 - 605. [Abstract] [Full Text] [PDF]

				M. L. Irwin, A. McTiernan, L. Bernstein, F. D. Gilliland, R. Baumgartner, K. Baumgartner, and R. Ballard-Barbash Relationship of Obesity and Physical Activity with C-Peptide, Leptin, and Insulin-Like Growth Factors in Breast Cancer Survivors Cancer Epidemiol. Biomarkers Prev., December 1, 2005; 14(12): 2881 - 2888. [Abstract] [Full Text] [PDF]

				C. Mulhall, R. A. Hegele, H. Cao, D. Tritchler, M. Yaffe, and N. F. Boyd Pituitary Growth Hormone and Growth Hormone-Releasing Hormone Receptor Genes and Associations with Mammographic Measures and Serum Growth Hormone Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2648 - 2654. [Abstract] [Full Text] [PDF]

				L. M. Morimoto, P. A. Newcomb, E. White, J. Bigler, and J. D. Potter Variation in Plasma Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3: Genetic Factors Cancer Epidemiol. Biomarkers Prev., June 1, 2005; 14(6): 1394 - 1401. [Abstract] [Full Text] [PDF]

				C. Diorio, M. Pollak, C. Byrne, B. Masse, N. Hebert-Croteau, M. Yaffe, G. Cote, S. Berube, C. Morin, and J. Brisson Insulin-Like Growth Factor-I, IGF-Binding Protein-3, and Mammographic Breast Density Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1065 - 1073. [Abstract] [Full Text] [PDF]

				E. S. Schernhammer, J. M. Holly, M. N. Pollak, and S. E. Hankinson Circulating Levels of Insulin-like Growth Factors, their Binding Proteins, and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., March 1, 2005; 14(3): 699 - 704. [Abstract] [Full Text] [PDF]

				J. A Lavigne, D. J Baer, H. H Wimbrow, P. S Albert, E. D Brown, J. T Judd, W. S Campbell, C. A Giffen, J. F Dorgan, T. J Hartman, et al. Effects of alcohol on insulin-like growth factor I and insulin-like growth factor binding protein 3 in postmenopausal women Am. J. Clinical Nutrition, February 1, 2005; 81(2): 503 - 507. [Abstract] [Full Text] [PDF]

				O. Fletcher, L. Gibson, N. Johnson, D. R. Altmann, J. M.P. Holly, A. Ashworth, J. Peto, and I. d. S. Silva Polymorphisms and Circulating Levels in the Insulin-Like Growth Factor System and Risk of Breast Cancer: A Systematic Review Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 2 - 19. [Abstract] [Full Text] [PDF]

				S. Rinaldi, R. Kaaks, A. Zeleniuch-Jacquotte, A. A. Arslan, R. E. Shore, K. L. Koenig, L. Dossus, E. Riboli, P. Stattin, A. Lukanova, et al. Insulin-Like Growth Factor-I, IGF Binding Protein-3, and Breast Cancer in Young Women: A Comparison of Risk Estimates Using Different Peptide Assays Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 48 - 52. [Abstract] [Full Text] [PDF]

				D. W. Voskuil, A. Vrieling, L. J. van't Veer, E. Kampman, and M. A. Rookus The Insulin-like Growth Factor System in Cancer Prevention: Potential of Dietary Intervention Strategies Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 195 - 203. [Abstract] [Full Text] [PDF]

				N. Tran, B. S. Bharaj, E. P. Diamandis, M. Smith, B. D. L. Li, and H. Yu Short Tandem Repeat Polymorphism and Cancer Risk: Influence of Laboratory Analysis on Epidemiologic Findings Cancer Epidemiol. Biomarkers Prev., December 1, 2004; 13(12): 2133 - 2140. [Abstract] [Full Text] [PDF]

				S. M. Gapstur, P. Kopp, B. C-H. Chiu, P. H. Gann, L. A. Colangelo, and K. Liu Longitudinal Associations of Age, Anthropometric and Lifestyle Factors with Serum Total Insulin-Like Growth Factor-I and IGF Binding Protein-3 Levels in Black and White Men: the CARDIA Male Hormone Study Cancer Epidemiol. Biomarkers Prev., December 1, 2004; 13(12): 2208 - 2216. [Abstract] [Full Text] [PDF]

				J. A. Lavigne, H. H. Wimbrow, B. A. Clevidence, P. S. Albert, M. E. Reichman, W. S. Campbell, J. C. Barrett, S. D. Hursting, J. T. Judd, and P. R. Taylor Effects of Alcohol and Menstrual Cycle on Insulin-like Growth Factor-I and Insulin-like Growth Factor Binding Protein-3 Cancer Epidemiol. Biomarkers Prev., December 1, 2004; 13(12): 2264 - 2267. [Abstract] [Full Text] [PDF]

				H. Gronbaek, A. Flyvbjerg, L. Mellemkjaer, A. Tjonneland, J. Christensen, H. Toft Sorensen, and K. Overvad Serum Insulin-Like Growth Factors, Insulin-Like Growth Factor Binding Proteins, and Breast Cancer Risk in Postmenopausal Women Cancer Epidemiol. Biomarkers Prev., November 1, 2004; 13(11): 1759 - 1764. [Abstract] [Full Text] [PDF]

				Z. Ren, Q. Cai, X.-O. Shu, H. Cai, C. Li, H. Yu, Y.-T. Gao, and W. Zheng Genetic Polymorphisms in the IGFBP3 Gene: Association with Breast Cancer Risk and Blood IGFBP-3 Protein Levels among Chinese Women Cancer Epidemiol. Biomarkers Prev., August 1, 2004; 13(8): 1290 - 1295. [Abstract] [Full Text] [PDF]

				M. Freemark Editorial: Growth Hormone Treatment of "Idiopathic Short Stature": Not So Fast J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3138 - 3139. [Full Text] [PDF]

				B. L. Dake, M. Boes, L. A. Bach, and R. S. Bar Effect of an Insulin-Like Growth Factor Binding Protein Fusion Protein on Thymidine Incorporation in Neuroblastoma and Rhabdomyosarcoma Cell Lines Endocrinology, July 1, 2004; 145(7): 3369 - 3374. [Abstract] [Full Text] [PDF]

				S. Baron-Hay, F. Boyle, A. Ferrier, and C. Scott Elevated Serum Insulin-Like Growth Factor Binding Protein-2 as a Prognostic Marker in Patients with Ovarian Cancer Clin. Cancer Res., March 1, 2004; 10(5): 1796 - 1806. [Abstract] [Full Text] [PDF]

				J. J. Pereira, T. Meyer, S. E. Docherty, H. H. Reid, J. Marshall, E. W. Thompson, J. Rossjohn, and J. T. Price Bimolecular Interaction of Insulin-Like Growth Factor (IGF) Binding Protein-2 with {alpha}v{beta}3 Negatively Modulates IGF-I-Mediated Migration and Tumor Growth1 Cancer Res., February 1, 2004; 64(3): 977 - 984. [Abstract] [Full Text] [PDF]

				D. Gunnell, S. E. Oliver, J. L. Donovan, T. J. Peters, D. Gillatt, R. Persad, F. C. Hamdy, D. E. Neal, and J. M. P. Holly Do Height-Related Variations in Insulin-Like Growth Factors Underlie the Associations of Stature with Adult Chronic Disease? J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 213 - 218. [Abstract] [Full Text] [PDF]

				R. A. Krajcik, S. Massardo, and N. Orentreich No Association between Serum Levels of Tumor Necrosis Factor-{alpha} (TNF-{alpha}) or the Soluble Receptors sTNFR1 and sTNFR2 and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., September 1, 2003; 12(9): 945 - 946. [Full Text] [PDF]