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A combined analysis of genome-wide association studies in breast cancer |
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| Authors: | Jingmei Li Keith Humphreys Tuomas Heikkinen Kristiina Aittom?ki Carl Blomqvist Paul D. P. Pharoah Alison M. Dunning Shahana Ahmed Maartje J. Hooning John W. M. Martens Ans M. W. van den Ouweland Lars Alfredsson Aarno Palotie Leena Peltonen-Palotie Astrid Irwanto Hui Qi Low Garrett H. K. Teoh Anbupalam Thalamuthu Douglas F. Easton Heli Nevanlinna Jianjun Liu Kamila Czene Per Hall |
| Affiliation: | 1. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, P.O. Box 281, 17177, Stockholm, Sweden 2. Human Genetics, Genome Institute of Singapore, 60 Biopolis Street, #02-01 Genome, Singapore, 138672, Singapore 3. Department of Obstetrics and Gynecology, Helsinki University Central Hospital, P.O. Box 700, 00029 HUS, Helsinki, Finland 4. Department of Clinical Genetics, Helsinki University Central Hospital, P.O. Box 140, 00029 HUS, Helsinki, Finland 5. Department of Oncology, Helsinki University Central Hospital, P.O. Box 180, 00029 HUS, Helsinki, Finland 6. Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK 7. Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK 8. Department of Medical Oncology, Rotterdam Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, Netherlands 9. Department of Clinical Genetics, Rotterdam Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, Netherlands 10. Institute of Environmental Medicine, Karolinska Institutet, P.O. Box 281, Stockholm, 17177, Sweden 11. Institute for Molecular Medicine Finland, FIMM, University of Helsinki, P.O. Box 20, 00014, Helsinki, Finland 12. Public Health Genomics Unit, National Institute for Health and Welfare, P.O. Box 30, 00271, Helsinki, Finland 13. Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK 14. Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA |
| 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. |
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