BioMed Central | Full text | Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density

Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density
Margarethe Biong1 , Inger T Gram2 , Ilene Brill3 , Fredrik Johansen1 , Hiroko K Solvang1,4 , Grethe IG Alnaes1 , Toril Fagerheim5 , Yngve Bremnes2 , Stephen J Chanock6,7 , Laurie Burdett7 , Meredith Yeager7 , Giske Ursin8,9 and Vessela N Kristensen1,10

1 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Montebello 0310, Oslo, Norway

2 Institute of Community Medicine, University of Tromsø, Breivika, Norway

3 University of Alabama at Birmingham, School of Public Health, Department of Epidemiology, Birmingham, Alabama, USA

4 Department of Biostatistics, Institute of Basic Medical Science, University of Oslo, Oslo, Norway

5 Department of Genetics, University Hospital of North Norway, Tromsø; Norway

6 NCI, NIH, Pediatric Branch, Bethesda, USA

7 Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, Bethesda, MD, 20892, USA

8 Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

9 Department of Preventive Medicine University of Southern California Keck School of Medicine, Los Angeles, CA, USA

10 Faculty of Medicine, (Faculty Division Ahus), UiO, Oslo, Norway

author email corresponding author email

BMC Medical Genomics 2010, 3:9doi:10.1186/1755-8794-3-9

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1755-8794/3/9

Received: 7 August 2009
Accepted: 19 March 2010
Published: 19 March 2010

© 2010 Biong et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Background
Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a woman's life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here.

Methods
Samples from 964 postmenopausal Norwegian women aged 55-71 years were collected as a part of the Tromsø Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI). The main statistical analyses were conducted with the PROC HAPLOTYPE procedure within SAS/GENETICS™ (SAS 9.1.3).

Results
The haplotype analysis revealed six haploblocks within the studied genes. Of those, four had significant associations with circulating levels of IGF1 or IGFBP3 and/or mammographic density. One haplotype variant in the IGF1 gene was found to be associated with mammographic density. Within the IGF2 gene one haplotype variant was associated with levels of both IGF1 and IGFBP3. Two haplotype variants in the IGF2R were associated with the level of IGF1. Both variants of the IGFBP3 haplotype were associated with the IGFBP3 level and indicate regulation in cis.

Conclusion
Polymorphisms within the IGF1 gene and related genes were associated with plasma levels of IGF1, IGFBP3 and mammographic density in this study of postmenopausal women.



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BioMed Central | Full text | Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density