title: Gene-based analysis of the fibroblast growth factor receptor signaling pathway in relation to breast cancer in African American women: the AMBER consortium.
abstract: We conducted gene-based analysis in 26 genes in the FGFR signaling pathway to identify genes carrying genetic variation affecting risk of breast cancer and the specific estrogen receptor (ER) subtypes. Tagging single-nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina Exome Array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 3237 SNPs in 3663 breast cancer cases (including 1983 ER-positive, and 1098 ER-negative) and 4687 controls from the African American Breast Cancer Epidemiology and Risk consortium, a collaborative project of four large studies of breast cancer in African American women (Carolina Breast Cancer Study, Black Women's Health Study, Women's Circle of Health Study, and Multiethnic Cohort). We used a multi-locus adaptive joint (AdaJoint) test to determine the association of each gene in the FGFR signaling pathway with overall breast cancer and ER subtypes. The FGF1 gene was significantly associated with risk of ER-negative breast cancer (P = 0.001). The FGFR2 gene was associated with risk of overall breast cancer (P = 0.002) and ER-positive breast cancer (P = 0.002). The FGF1 gene affects risk of ER-negative breast cancer in African American women. We confirmed the association of the FGFR2 gene with risk of overall and ER-positive breast cancer. These results highlight the importance of the FGFR signaling pathway in the pathogenesis of breast cancer, and suggest that different genes in the same pathway may be associated with different ER breast cancer subtypes.
authors.affiliation: Slone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, Boston, MA, 02215, USA. eruiznar@bu.edu.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Ruiz-Narváez
authors.affiliation: Slone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, Boston, MA, 02215, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Haddad
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Lunetta
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Epidemiology, Gillings School of Global Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Jeannette T
authors.initials: JT
authors.lastname: Bensen
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Lara E
authors.initials: LE
authors.lastname: Sucheston-Campbell
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Hong
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Department of Epidemiology, Gillings School of Global Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Olshan
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.affiliation: Slone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, Boston, MA, 02215, USA.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Palmer
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics*; D055815:Young Adult
chemical_list: D011960:Receptors, Estrogen; D016220:Fibroblast Growth Factor 1; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: African Americans; Breast cancer; FGF/FGFR pathway; Gene-based analysis