title: Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium.
abstract: The insulin/insulin-like growth factor (IGF) system and related pathways such as growth hormone, and leptin signaling have a key role in cancer development. It is unclear how germline variation in these pathways affects breast cancer risk. We conducted gene-based analyses of 184 genes in the insulin/IGF, growth hormone, and leptin pathways to identify genetic variation associated with risk of breast cancer overall, and for estrogen receptor (ER) subtypes. Tag single-nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina SNP array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 91,627 SNPs genotyped or imputed in 3,663 breast cancer cases, (1,983 ER-positive and 1,098 ER-negative) and 4,687 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 test to determine the association of each gene with overall breast cancer and ER subtypes. The most significant gene associations (P≤ 0.01) wereBAIAP2andCALM2for overall breast cancer;BAIAP2andCSNK2A1for ER+breast cancer; andBRAF,BAD, andMAPK3for ER-breast cancer. The association ofBADwith ER-breast cancer was explained by a two-SNP risk model; all other associations were best explained by one-SNP risk models. In total, six genes and seven SNPs had suggestive associations with overall breast cancer or ER subtypes in African-American women.
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, MA, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Ruiz-Narváez
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: Chi-Chen
authors.initials: CC
authors.lastname: Hong
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, MA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Haddad
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 Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Ting-Yuan David
authors.initials: TD
authors.lastname: Cheng
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: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
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: Melissa A
authors.initials: MA
authors.lastname: Troester
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, Boston, MA, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Rosenberg
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, MA, USA.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Palmer