title: Genetic variation in IGFBP2 and IGFBP5 is associated with breast cancer in populations of African descent.
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.
authors.affiliation: Department of Epidemiology, University of California Irvine, 224 Irvine Hall, Irvine, CA, 92697-7550, USA.
authors.forename: Chad P
authors.initials: CP
authors.lastname: Garner
authors.forename: Yuan C
authors.initials: YC
authors.lastname: Ding
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.forename: Sue A
authors.initials: SA
authors.lastname: Ingles
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Dezheng
authors.initials: D
authors.lastname: Huo
authors.forename: Clement
authors.initials: C
authors.lastname: Adebamowo
authors.forename: Temidayo
authors.initials: T
authors.lastname: Ogundiran
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044383:Black People / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics*; D008875:Middle Aged; D009549:Nigeria / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; D018975:Insulin-Like Growth Factor Binding Protein 5