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Genetic variation in IGFBP2 and IGFBP5 is associated with breast cancer in populations of African descent

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Abstract

The insulin-like growth factor (IGF) signaling pathway is thought to play a major role in the etiology of breast cancer. Although incidence rates of breast cancer overall are lower in African Americans than in Caucasians, African-American women have a higher incidence under age 40 years, are diagnosed with more advanced disease, and have poorer prognosis. We investigated the association of breast cancer and genetic variants in genes in the IGF signaling pathway in a population-based case–control study of African-American women. We found significant associations at a locus encompassing parts of the IGFBP2 and IGFBP5 genes on chromosome 2q35, which we then replicated in a case–control study of Nigerian women. Based on those initial findings, we genotyped a total of 34 single nucleotide polymorphisms (SNPs) across the region in both study populations. Statistically significant associations with breast cancer were observed across approximately 50 kb of DNA sequence encompassing three exons in the 3′ end of IGFBP2 and three exons in the 3′ end of IGFBP5. SNPs were associated with breast cancer risk with P values as low as P = 0.0038 and P = 0.01 in African-Americans and Nigerians, respectively. This study is the first to report associations between genetic variants in IGFBP2 and IGFBP5 and breast cancer risk.

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Acknowledgments

We thank Jocelyn Koo for data management and Karen Kelly and Megan Rounds for genotyping, and Kavita Renduchintala, Ming Li, and Aileen Sy for help with the genotyping. We thank the women who participated in this research. This work was supported by the California Breast Cancer Program 9PB-0142 (to SLN). The multi-ethnic case-control study was supported by grant CA77305 from the National Cancer Institute (NCI) and grant 17-96-1-6071 by the U.S. Department of Defense (to EMJ). The Northern California Family Registry for Breast Cancer was supported by the NCI under RFA#CA95-003 through a cooperative agreement with the Northern California Cancer Center (to EMJ). Collection of the Nigerian case-control population was funded by NCI CA-RO1 89085-01A and the Ralph and Marion Falk Medical Research Trust (to OIO).

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Authors and Affiliations

  1. Department of Epidemiology, University of California Irvine, 224 Irvine Hall, Irvine, CA, 92697-7550, USA

    Chad P. Garner, Yuan C. Ding & Susan L. Neuhausen

  2. Northern California Cancer Center, Fremont, CA, USA

    Esther M. John

  3. Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Sue A. Ingles

  4. Department of Medicine, University of Chicago, Chicago, IL, USA

    Olufunmilayo I. Olopade

  5. Department of Health Studies, University of Chicago, Chicago, IL, USA

    Dezheng Huo

  6. Department of Surgery, Division of Oncology, College of Medicine, University of Ibadan, Ibadan, Nigeria

    Clement Adebamowo & Temidayo Ogundiran

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  1. Chad P. Garner
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Correspondence to Susan L. Neuhausen.

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Garner, C.P., Ding, Y.C., John, E.M. et al. Genetic variation in IGFBP2 and IGFBP5 is associated with breast cancer in populations of African descent. Hum Genet 123, 247–255 (2008). https://doi.org/10.1007/s00439-008-0468-x

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