A combined analysis of genome-wide association studies in breast cancer

JM Li, K Humphreys, T Heikkinen, K Aittomaki, C Blomqvist, PDP Pharoah, AM Dunning, S (Shahana) Ahmed, Maartje Hooning, John Martens, Ans van den Ouweland, L Alfredsson, A Palotie, L Peltonen-Palotie, A Irwanto, HQ Low, GHK Teoh, A Thalamuthu, DF Easton, H NevanlinnaJJ Liu, K Czene, P Hall

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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.
Original languageUndefined/Unknown
Pages (from-to)717-727
Number of pages11
JournalBreast Cancer Research and Treatment
Issue number3
Publication statusPublished - 2011

Research programs

  • EMC MGC-02-96-01
  • EMC MM-03-86-01

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