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

被引：24

作者：

Biong, Margarethe ^{[1
]}

Gram, Inger T. ^{[2
]}

Brill, Ilene ^{[3
]}

Johansen, Fredrik ^{[1
]}

Solvang, Hiroko K. ^{[1
,4
]}

Alnaes, Grethe I. G. ^{[1
]}

Fagerheim, Toril ^{[5
]}

Bremnes, Yngve ^{[2
]}

Chanock, Stephen J. ^{[6
,7
]}

Burdett, Laurie ^{[7
]}

Yeager, Meredith ^{[7
]}

Ursin, Giske ^{[8
,9
]}

Kristensen, Vessela N. ^{[1
,10
]}

机构：

[1] Radiumhosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway

[2] Univ Tromso, Inst Community Med, Breivika, Norway

[3] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA

[4] Univ Oslo, Inst Basic Med Sci, Dept Biostat, Oslo, Norway

[5] Univ Hosp N Norway, Dept Genet, Tromso, Norway

[6] NCI, NIH, Pediat Branch, Bethesda, MD 20892 USA

[7] NCI, Core Genotyping Facil, Adv Technol Ctr, Bethesda, MD 20892 USA

[8] Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway

[9] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[10] UiO, Fac Div Ahus, Fac Med, Oslo, Norway

来源：

BMC MEDICAL GENOMICS | 2010年 / 3卷

关键词：

BREAST-CANCER RISK; POSTMENOPAUSAL HORMONE-THERAPY; I IGF-I; CIRCULATING LEVELS; GENETIC POLYMORPHISMS; SERUM-LEVELS; ASSOCIATION; IGFBP-3; WOMEN; HERITABILITY;

D O I：

10.1186/1755-8794-3-9

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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 Tromso 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 (TM) (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.

引用

页数：13

共 69 条

[1]

IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer [J].

Al-Zahrani, A ;

Sandhu, MS ;

Luben, RN ;

Thompson, D ;

Baynes, C ;

Pooley, KA ;

Luccarini, C ;

Munday, H ;

Perkins, B ;

Smith, P ;

Pharoah, PDP ;

Wareham, NJ ;

Easton, DF ;

Ponder, BAJ ;

Dunning, AM .

HUMAN MOLECULAR GENETICS, 2006, 15 (01) :1-10

[2]

A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk [J].

Allen, NE ;

Roddam, AW ;

Allen, DS ;

Fentiman, IS ;

Silva, ID ;

Peto, J ;

Holly, JMP ;

Key, TJ .

BRITISH JOURNAL OF CANCER, 2005, 92 (07) :1283-1287

[3]

Insulin like growth factor-I in relation to premenopausal ductal carcinoma in situ of the breast [J].

Bohlke, K ;

Cramer, DW ;

Trichopoulos, D ;

Mantzoros, CS .

EPIDEMIOLOGY, 1998, 9 (05) :570-573

[4]

The acid-labile subunit (ALS) of the 150 kDa IGF-binding protein complex: an important but forgotten component of the circulating IGF system [J].

Boisclair, YR ;

Rhoads, RP ;

Ueki, I ;

Wang, J ;

Ooi, GT .

JOURNAL OF ENDOCRINOLOGY, 2001, 170 (01) :63-70

[5]

AN ANALYSIS OF TRANSFORMATIONS [J].

BOX, GEP ;

COX, DR .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1964, 26 (02) :211-252

[6]

Mammographic breast density as an intermediate phenotype for breast cancer [J].

Boyd, NF ;

Rommens, JM ;

Vogt, K ;

Lee, V ;

Hopper, JL ;

Yaffe, MJ ;

Paterson, AD .

LANCET ONCOLOGY, 2005, 6 (10) :798-808

[7]

Heritability of mammographic density, a risk factor for breast cancer [J].

Boyd, NF ;

Dite, GS ;

Stone, J ;

Gunasekara, A ;

English, DR ;

McCredie, MRE ;

Giles, GG ;

Tritchler, D ;

Chiarelli, A ;

Yaffe, MJ ;

Hopper, JL .

NEW ENGLAND JOURNAL OF MEDICINE, 2002, 347 (12) :886-894

[8]

The association of breast mitogens with mammographic densities [J].

Boyd, NF ;

Stone, J ;

Martin, LJ ;

Jong, R ;

Fishel, E ;

Yaffe, M ;

Hammond, G ;

Minkin, S .

BRITISH JOURNAL OF CANCER, 2002, 87 (08) :876-882

[9]

Different measures of smoking exposure and mammographic density in postmenopausal Norwegian women: a cross-sectional study [J].

Bremnes, Yngve ;

Ursin, Giske ;

Bjurstam, Nils ;

Gram, Inger T. .

BREAST CANCER RESEARCH, 2007, 9 (05) :R73

[10]

Endogenous sex hormones, prolactin and mammographic density in postmenopausal Norwegian women [J].

Bremnes, Yngve ;

Ursin, Giske ;

Bjurstam, Nils ;

Rinaldi, Sabina ;

Kaaks, Rudolf ;

Gram, Inger T. .

INTERNATIONAL JOURNAL OF CANCER, 2007, 121 (11) :2506-2511

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