title: Hormone-related pathways and risk of breast cancer subtypes in African American women.
abstract: We sought to investigate genetic variation in hormone pathways in relation to risk of overall and subtype-specific breast cancer in women of African ancestry (AA). Genotyping and imputation yielded data on 143,934 SNPs in 308 hormone-related genes for 3663 breast cancer cases (1098 ER-, 1983 ER+, 582 ER unknown) and 4687 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. AMBER includes data from four large studies of AA women: the Carolina Breast Cancer Study, the Women's Circle of Health Study, the Black Women's Health Study, and the Multiethnic Cohort Study. Pathway- and gene-based analyses were conducted, and single-SNP tests were run for the top genes. There were no strong associations at the pathway level. The most significantly associated genes were GHRH, CALM2, CETP, and AKR1C1 for overall breast cancer (gene-based nominal p ≤ 0.01); NR0B1, IGF2R, CALM2, CYP1B1, and GRB2 for ER+ breast cancer (p ≤ 0.02); and PGR, MAPK3, MAP3K1, and LHCGR for ER- disease (p ≤ 0.02). Single-SNP tests for SNPs with pairwise linkage disequilibrium r (2) < 0.8 in the top genes identified 12 common SNPs (in CALM2, CETP, NR0B1, IGF2R, CYP1B1, PGR, MAPK3, and MAP3K1) associated with overall or subtype-specific breast cancer after gene-level correction for multiple testing. Rs11571215 in PGR (progesterone receptor) was the SNP most strongly associated with ER- disease. We identified eight genes in hormone pathways that contain common variants associated with breast cancer in AA women after gene-level correction for multiple testing.
authors.affiliation: Slone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, Boston, MA, 02215, USA. sahaddad@bu.edu.
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: Slone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, Boston, MA, 02215, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Ruiz-Narváez
authors.affiliation: Department of Epidemiology, 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: Chi-Chen
authors.initials: CC
authors.lastname: Hong
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: Song
authors.initials: S
authors.lastname: Yao
authors.affiliation: Cancer Prevention and Control, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
authors.affiliation: Slone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, Boston, MA, 02215, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Rosenberg
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, 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, 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* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000235:genetics*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D012739:Gonadal Steroid Hormones; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: African Americans; Breast cancer; Genetics; Hormones; Pathways