title: A combined analysis of genome-wide association studies in breast cancer.
abstract: In an attempt to identify common disease susceptibility alleles for breast cancer, we performed a combined analysis of three genome-wide association studies (GWAS), involving 2,702 women of European ancestry with invasive breast cancer and 5,726 controls. Tests for association were performed for 285,984 SNPs. Evidence for association with SNPs in genes in specific pathways was assessed using a permutation-based approach. We confirmed associations with loci reported by previous GWAS on 1p11.2, 2q35, 3p, 5p12, 8q24, 10q23.13, 14q24.1 and 16q. Six SNPs with the strongest signals of association with breast cancer, and which have not been reported previously, were typed in two further studies; however, none of the associations could be confirmed. Suggestive evidence for an excess of associations was found for genes involved in the regulation of actin cytoskeleton, glycan degradation, alpha-linolenic acid metabolism, circadian rhythm, hematopoietic cell lineage and drug metabolism. Androgen and oestrogen metabolism, a pathway previously found to be associated with the development of postmenopausal breast cancer, was marginally significant (P = 0.051 [unadjusted]). These results suggest that further analysis of SNPs in these pathways may identify associations that would be difficult to detect through agnostic single SNP analyses. More effort focused in these aspects of oncology can potentially open up promising avenues for the understanding of breast cancer and its prevention.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, 17177 Stockholm, Sweden.
authors.forename: Jingmei
authors.initials: J
authors.lastname: Li
authors.forename: Keith
authors.initials: K
authors.lastname: Humphreys
authors.forename: Tuomas
authors.initials: T
authors.lastname: Heikkinen
authors.forename: Kristiina
authors.initials: K
authors.lastname: Aittomäki
authors.forename: Carl
authors.initials: C
authors.lastname: Blomqvist
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Shahana
authors.initials: S
authors.lastname: Ahmed
authors.forename: Maartje J
authors.initials: MJ
authors.lastname: Hooning
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.forename: Ans M W
authors.initials: AM
authors.lastname: van den Ouweland
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen-Palotie
authors.forename: Astrid
authors.initials: A
authors.lastname: Irwanto
authors.forename: Hui Qi
authors.initials: HQ
authors.lastname: Low
authors.forename: Garrett H K
authors.initials: GH
authors.lastname: Teoh
authors.forename: Anbupalam
authors.initials: A
authors.lastname: Thalamuthu
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Heli
authors.initials: H
authors.lastname: Nevanlinna
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Kamila
authors.initials: K
authors.lastname: Czene
authors.forename: Per
authors.initials: P
authors.lastname: Hall
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D019295:Computational Biology; D003627:Data Interpretation, Statistical; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015233:Models, Statistical; D017720:Molecular Epidemiology; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers