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Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast density

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Introduction High breast density is one of the strongest known risk factors for developing breast cancer. Insulin-like growth factor I (IGF-I) is a strong mitogen and has been suggested to increase breast cancer risk by increasing the amount of dense tissue in the female breast. Objectives We wanted to investigate the effect of common variation in the IGF-1 gene on serum IGF-I levels and on breast density. Design and methods Mammograms and blood samples of 1,928 premenopausal participants of the Dutch Prospect-EPIC cohort were collected at baseline. Using a haplotype tagging approach, 16 single nucleotide polymorphisms (SNP) from three blocks covering the IGF-1 gene were genotyped in all study participants. Breast density was assessed using a quantitative computer-assisted method. For a subgroup of women, who went through menopause within 5 years after recruitment (n = 656), premenopausal IGF-I levels and additionally postmenopausal breast density were determined. False positive report probabilities (FPRP) for statistically significant relations were calculated using the Wacholder method. Results The minor alleles of five SNPs in block 3 were significantly associated with elevated levels of IGF-I (rs9989002, rs2033178, rs7136446, rs978458, rs6220; P-values: 0.01–0.04). The same SNPs were related with modestly higher percent breast density before menopause and—in the subgroup of women that became postmenopausal during follow-up—with a modestly higher percent breast density after menopause. The most significant result, i.e. the relation between rs6220 and IGF-I levels, had an FPRP  <0.5 assuming prior probabilities of 0.01 and higher. Conclusion Common genetic variation in the IGF-1 gene is related to circulating levels of IGF-I, but the relationship with breast density is indecisive.

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Acknowledgements

This study was supported by Grant Number 2002/11 of the World Cancer Research fund (WCRF).

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Authors and Affiliations

  1. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands

    Martijn Verheus, Diederick E. Grobbee, Petra H. M. Peeters & Carla H. van Gils

  2. Genetic Epidemiology Group, International Agency for Research on Cancer (IARC-WHO), Lyon, France

    James D. McKay

  3. Epidemiology Methods and Support Group, International Agency for Research on Cancer (IARC-WHO), Lyon, France

    Carine Biessy

  4. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Rudolf Kaaks

  5. Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Federico Canzian

  6. Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umea, Sweden

    Mattias Johansson

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  1. Martijn Verheus
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  2. James D. McKay
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Correspondence to Martijn Verheus.

Appendix

Appendix

Appendix 1 Associations between SNPs and postmenopausal breast measures, in women who became postmenopausal at time of follow-up (n = 656)
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Appendix 2 Probes and primers used for genotyping of haplotype tagging SNPs
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Verheus, M., McKay, J.D., Kaaks, R. et al. Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast density. Breast Cancer Res Treat 112, 109–122 (2008). https://doi.org/10.1007/s10549-007-9827-x

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  • DOI: https://doi.org/10.1007/s10549-007-9827-x

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