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Association between IGF1 CA microsatellites and mammographic density, anthropometric measures, and circulating IGF-I levels in premenopausal Caucasian women

  • Epidemiology
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Abstract

Background Results from several studies indicate that mammographic density, a strong risk factor for breast cancer, is greater in premenopausal women with higher circulating IGF-I levels. Both mammographic density and circulating IGF-I levels appear to be partly heritable traits. We hypothesized that in premenopausal women, IGF1 variants are associated with circulating IGF-I concentration, which in turn influences variation in breast density. Therefore, we examined the association of IGF1 polymorphisms with circulating IGF-I levels and mammographic density. Methods Percentage density, amounts of dense and non-dense (fat) tissue, IGF-I levels, and BMI were measured in 163 premenopausal women. Three CA repeat polymorphisms were genotyped, one each at the 5′ and 3′ ends of IGF1 and one in intron 2. Results The number of 19 alleles at the 5′ polymorphism was associated with lower circulating levels of IGF-I (P = 0.02), whereas the number of 185 alleles at the 3′ polymorphism was associated with higher percentage density (P = 0.03) and a smaller amount of non-dense tissue (P = 0.02). The strength of the effect of the 185 allele at 3′ on percentage density was greatly reduced and statistical significance lost when BMI was included in regression models. Conclusions Our results suggest an association between the number of 185 alleles at 3′ with percentage density. This association appears to be mediated by body composition and particularly body fat, as indicated by the association of 3′ IGF1 genotype with non-dense (fat) tissue and the mediating effect of BMI on the association of 3′ genotype with percentage density.

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Acknowledgements

We thank Hamdi Jarjanazi and Keith Wong for their contributions to this study.

Author information

Authors and Affiliations

  1. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    Gordon Fehringer, Julia A. Knight & Andrew D. Paterson

  2. Population Studies, Cancer Care Ontario, Toronto, ON, Canada

    Gordon Fehringer

  3. Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada

    Hilmi Ozcelik

  4. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada

    Hilmi Ozcelik

  5. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    Hilmi Ozcelik

  6. Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada

    Julia A. Knight

  7. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada

    Andrew D. Paterson

  8. Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, ON, Canada

    Norman F. Boyd

Authors
  1. Gordon Fehringer
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  2. Hilmi Ozcelik
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  4. Andrew D. Paterson
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  5. Norman F. Boyd
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Correspondence to Gordon Fehringer.

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Appendix: primers and primer positions

Appendix: primers and primer positions

Primers

  • 5′ polymorphism: 5′-GCTAGCCAGCTGGTGTTATT-3′, 5′-ACCACTCTGGGAGAAGGGTA-3′

  • Intron 2 polymorphism: 5′ CATACTTCTTAGCTCCTCAGG-3′, 5′-CCCTCACAGAAAGCAGAA-3′

  • 3′ Polymorphism: 5′-CTTTTTAAGATGAGGCAGTTCC-3′, 5′-GATTTCTTTTCAGTATTCCATTGG-3′

Primer positions (corresponding to contig NT_019546.15 of build 35.1 of the NCBI’s genome annotation)

  • 5′ Polymorphism: 26,357,243-26,357,436

  • Intron 2 polymorphism: 26,332,059-26,332,274

  • 3′ Polymorphism: 26,275,038-26,275,220

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Fehringer, G., Ozcelik, H., Knight, J.A. et al. Association between IGF1 CA microsatellites and mammographic density, anthropometric measures, and circulating IGF-I levels in premenopausal Caucasian women. Breast Cancer Res Treat 116, 413–423 (2009). https://doi.org/10.1007/s10549-008-0146-7

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  • DOI: https://doi.org/10.1007/s10549-008-0146-7

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