Human Molecular Genetics

Human Molecular Genetics Advance Access published online on November 23, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi398

This Article FREE Full Text (PDF) Supplementary Material All Versions of this Article: 15/1/1    most recent ddi398v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Google Scholar Articles by Al-Zahrani, A. Articles by Dunning, A. M Search for Related Content PubMed PubMed Citation Articles by Al-Zahrani, A. Articles by Dunning, A. M Social Bookmarking          What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved
Received September 1, 2005
Revised October 14, 2005
Accepted October 14, 2005

Article

IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer

Ali Al-Zahrani ¹, Manjinder S Sandhu ², Robert N Luben ³, Deborah Thompson ⁴, Caroline Baynes ¹, Karen A. Pooley ¹, Craig Luccarini ¹, Hannah Munday ¹, Barbara Perkins ¹, Paula Smith ⁴, Paul DP Pharoah ¹, Nicholas J Wareham ⁵, Douglas F Easton ⁴, Bruce A J Ponder ¹, and Alison M Dunning ^{1 *}

¹ CR-UK Department of Oncology, Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK
² Department of Public Health and Primary Care, Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK
³ EPIC, Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK
⁴ CR-UK Genetic Epidemiology Unit, Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK
⁵ MRC Epidemiology Unit, Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK

^* To whom correspondence should be addressed.
Alison M Dunning, E-mail: alisond{at}srl.cam.ac.uk

	Abstract

Experimental and observational studies in humans and animals suggest that insulin-like growth factor 1 (IGF1) and its principle binding protein, IGFBP3, may influence breast cancer susceptibility. We have examined the association of 9 single nucleotide polymorphisms (SNPs) in the IGF1 gene and 4 in the IGFBP3 gene with circulating levels of their gene products in a population-based study of 600 middle-aged men and women, and in a breast cancer case-control study, comprised of up to 4,647 cases and 4,564 controls. All study participants are from the East Anglian region of England. SNPs were specifically chosen to tag all other known SNPs in each gene. Several SNPs in each gene are associated with both circulating levels of their respective proteins and with risk of breast cancer. In particular, the c allele of IGF1 SNP rs1520220 is associated with increased circulating IGF1 (r² = 2.1%, P-trend = 0.003) in females and an increased risk of breast cancer: Odds Ratio (OR)(cc/gg)  = 1.41; 95% Confidence Intervals (95%CIs) 1.11-1.79; P-trend = 0.03). The a allele of IGFBP3 SNP rs2854744 is associated with increased circulating IGFBP3 (r² = 9.7%, P < 10^-9) and a decreased risk of breast cancer: OR (aa/cc)  = 0.87; 95%CIs 0.77-0.99; P = 0.03). Our data indicate that common variants in the IGF1 and IGFBP3 genes are associated with differences in circulating levels of IGF1 and IGFBP3 and with breast cancer risk. More specifically and consistent with experimental models, our data suggest that higher IGF1 levels may increase the risk of breast cancer but higher IGFBP3 levels may be protective.

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				A. A. D'Aloisio, J. C. Schroeder, K. E. North, C. Poole, S. L. West, G. S. Travlos, and D. D. Baird IGF-I and IGFBP-3 Polymorphisms in Relation to Circulating Levels among African American and Caucasian Women Cancer Epidemiol. Biomarkers Prev., March 1, 2009; 18(3): 954 - 966. [Abstract] [Full Text] [PDF]

				E. F. Costalonga, S. R. Antonini, G. Guerra-Junior, B. B. Mendonca, I. J. P. Arnhold, and A. A. L. Jorge The -202 A Allele of Insulin-Like Growth Factor Binding Protein-3 (IGFBP3) Promoter Polymorphism Is Associated with Higher IGFBP-3 Serum Levels and Better Growth Response to Growth Hormone Treatment in Patients with Severe Growth Hormone Deficiency J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 588 - 595. [Abstract] [Full Text] [PDF]

				H. Suzuki, Y. Li, X. Dong, M. M. Hassan, J. L. Abbruzzese, and D. Li Effect of Insulin-Like Growth Factor Gene Polymorphisms Alone or In Interaction with Diabetes on the Risk of Pancreatic Cancer Cancer Epidemiol. Biomarkers Prev., December 1, 2008; 17(12): 3467 - 3473. [Abstract] [Full Text] [PDF]

				S. Lonn, N. Rothman, W. R. Shapiro, H. A. Fine, R. G. Selker, P. M. Black, J. S. Loeffler, A. A. Hutchinson, and P. D. Inskip Genetic variation in insulin-like growth factors and brain tumor risk Neuro-oncol, August 1, 2008; 10(4): 553 - 559. [Abstract] [Full Text] [PDF]

				H-L Wong, W-P Koh, N M Probst-Hensch, D Van den Berg, M C Yu, and S A Ingles Insulin-like growth factor-1 promoter polymorphisms and colorectal cancer: a functional genomics approach Gut, August 1, 2008; 57(8): 1090 - 1096. [Abstract] [Full Text] [PDF]

				Y. Mizuno, N. Hattori, S.-i. Kubo, S. Sato, K. Nishioka, T. Hatano, H. Tomiyama, M. Funayama, Y. Machida, and H. Mochizuki Progress in the pathogenesis and genetics of Parkinson's disease Phil Trans R Soc B, June 27, 2008; 363(1500): 2215 - 2227. [Abstract] [Full Text] [PDF]

				C. Palles, N. Johnson, B. Coupland, C. Taylor, J. Carvajal, J. Holly, I. S. Fentiman, I. dos Santos Silva, A. Ashworth, J. Peto, et al. Identification of genetic variants that influence circulating IGF1 levels: a targeted search strategy Hum. Mol. Genet., May 15, 2008; 17(10): 1457 - 1464. [Abstract] [Full Text] [PDF]

				C. Diorio, J. Brisson, S. Berube, and M. Pollak Genetic Polymorphisms Involved in Insulin-like Growth Factor (IGF) Pathway in Relation to Mammographic Breast Density and IGF Levels Cancer Epidemiol. Biomarkers Prev., April 1, 2008; 17(4): 880 - 888. [Abstract] [Full Text] [PDF]

				V. M. Chia, L. C. Sakoda, B. I. Graubard, M. V. Rubertone, S. J. Chanock, R. L. Erickson, and K. A. McGlynn Risk of Testicular Germ Cell Tumors and Polymorphisms in the Insulin-Like Growth Factor Genes Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 721 - 726. [Abstract] [Full Text] [PDF]

				S. L. Deming, Z. Ren, Q. Cai, X.-O. Shu, W. Wen, J.-R. Long, Y.-T. Gao, and W. Zheng IGF-I and IGF-II Genetic Variation and Breast Cancer Risk in Chinese Women: Results from the Shanghai Breast Cancer Study Cancer Epidemiol. Biomarkers Prev., January 1, 2008; 17(1): 255 - 257. [Full Text] [PDF]

				J. Paquette, B. Bessette, E. Ledru, and C. Deal Identification of Upstream Stimulatory Factor Binding Sites in the Human IGFBP3 Promoter and Potential Implication of Adjacent Single-Nucleotide Polymorphisms and Responsiveness to Insulin Endocrinology, December 1, 2007; 148(12): 6007 - 6018. [Abstract] [Full Text] [PDF]

				A. J. Sigurdson, P. Bhatti, M. M. Doody, M. Hauptmann, L. Bowen, S. L. Simon, R. M. Weinstock, M. S. Linet, M. Rosenstein, M. Stovall, et al. Polymorphisms in Apoptosis- and Proliferation-Related Genes, Ionizing Radiation Exposure, and Risk of Breast Cancer among U.S. Radiologic Technologists Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 2000 - 2007. [Abstract] [Full Text] [PDF]

				I. Cheng, K. DeLellis Henderson, C. A. Haiman, L. N. Kolonel, B. E. Henderson, M. L. Freedman, and L. Le Marchand Genetic Determinants of Circulating Insulin-Like Growth Factor (IGF)-I, IGF Binding Protein (BP)-1, and IGFBP-3 Levels in a Multiethnic Population J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3660 - 3666. [Abstract] [Full Text] [PDF]

				J. Stone, L. C. Gurrin, G. B. Byrnes, C. J. Schroen, S. A. Treloar, E. J.D. Padilla, G. S. Dite, M. C. Southey, V. M. Hayes, and J. L. Hopper Mammographic Density and Candidate Gene Variants: A Twins and Sisters Study Cancer Epidemiol. Biomarkers Prev., July 1, 2007; 16(7): 1479 - 1484. [Abstract] [Full Text] [PDF]

				Y.-L. Low, A. M. Dunning, M. Dowsett, E. Folkerd, D. Doody, J. Taylor, A. Bhaniani, R. Luben, K.-T. Khaw, N. J. Wareham, et al. Phytoestrogen Exposure Is Associated with Circulating Sex Hormone Levels in Postmenopausal Women and Interact with ESR1 and NR1I2 Gene Variants Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 1009 - 1016. [Abstract] [Full Text] [PDF]

				The Breast Cancer Association Consortium Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium. J Natl Cancer Inst, October 4, 2006; 98(19): 1382 - 1396. [Abstract] [Full Text] [PDF]

				I. Cheng, K. L. Penney, D. O. Stram, L. Le Marchand, E. Giorgi, C. A. Haiman, L. N. Kolonel, M. Pike, J. Hirschhorn, B. E. Henderson, et al. Haplotype-Based Association Studies of IGFBP1 and IGFBP3 with Prostate and Breast Cancer Risk: The Multiethnic Cohort. Cancer Epidemiol. Biomarkers Prev., October 1, 2006; 15(10): 1993 - 1997. [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]

Online ISSN 1460-2083 - Print ISSN 0964-6906

Copyright © 2009 Oxford University Press

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics