2014
A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age
Publication
Publication
Cancer Epidemiology, Biomarkers & Prevention , Volume 23 - Issue 4 p. 658- 669
Early-onset breast cancer (EOBC) causes substantial loss of life and productivity, creating a major burden among women worldwide. We analyzed 1,265,548 Hapmap3 single-nucleotide polymorphisms (SNP) among a discovery set of 3,523 EOBC incident cases and 2,702 population control women ages ≤ 51 years. The SNPs with smallest P values were examined in a replication set of 3,470 EOBC cases and 5,475 control women. We also tested EOBC association with 19,684 genes by annotating each gene with putative functional SNPs, and then combining their P values to obtain a gene-based P value. We examined the gene with smallest P value for replication in 1,145 breast cancer cases and 1,142 control women. The combined discovery and replication sets identified 72 new SNPs associated with EOBC(P < 4 × 10-8) located in six genomic regions previously reported to contain SNPs associated largely with later-onset breast cancer (LOBC). SNP rs2229882 and 10 other SNPs on chromosome 5q11.2 remained associated (P < 6 × 10-4) after adjustment for the strongest published SNPs in the region. Thirty-two of the 82 currently known LOBC SNPs were associated with EOBC (P < 0.05). Low power is likely responsible for the remaining 50 unassociated known LOBC SNPs. The gene-based analysis identified an association between breast cancer and the phosphofructokinase-muscle (PFKM) gene on chromosome 12q13.11 that met the genome-wide gene-based threshold of 2.5 × 10-6. In conclusion, EOBC and LOBC seem to have similar genetic etiologies; the 5q11.2 region maycontain multiple distinct breast cancer loci; and the PFKM gene region is worthy of further investigation. These findings should enhance our understanding of the etiology of breast cancer.
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| doi.org/10.1158/1055-9965.EPI-13-0340, hdl.handle.net/1765/60021 | |
| Cancer Epidemiology, Biomarkers & Prevention | |
| Organisation | Department of Internal Medicine |
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Ahsan, H., Halpern, J., Kibriya, M., Pierce, A., Tong, L., Gamazon, E., … Whittemore, A. (2014). A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age. Cancer Epidemiology, Biomarkers & Prevention, 23(4), 658–669. doi:10.1158/1055-9965.EPI-13-0340 |
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