Human Genetics

, Volume 123, Issue 3, pp 247–255

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

Authors

  • Chad P. Garner
    • Department of EpidemiologyUniversity of California Irvine
  • Yuan C. Ding
    • Department of EpidemiologyUniversity of California Irvine
  • Esther M. John
    • Northern California Cancer Center
  • Sue A. Ingles
    • Keck School of MedicineUniversity of Southern California
  • Olufunmilayo I. Olopade
    • Department of MedicineUniversity of Chicago
  • Dezheng Huo
    • Department of Health StudiesUniversity of Chicago
  • Clement Adebamowo
    • Department of Surgery, Division of Oncology, College of MedicineUniversity of Ibadan
  • Temidayo Ogundiran
    • Department of Surgery, Division of Oncology, College of MedicineUniversity of Ibadan
    • Department of EpidemiologyUniversity of California Irvine
Original Investigation

DOI: 10.1007/s00439-008-0468-x

Cite this article as:
Garner, C.P., Ding, Y.C., John, E.M. et al. Hum Genet (2008) 123: 247. doi:10.1007/s00439-008-0468-x

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.

Copyright information

© Springer-Verlag 2008