Format

Send to

Choose Destination
Cancer Epidemiol Biomarkers Prev. 2014 Apr;23(4):658-69. doi: 10.1158/1055-9965.EPI-13-0340. Epub 2014 Feb 3.

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.

Author information

1
Authors' Affiliations: Center for Cancer Epidemiology and Prevention; Departments of Health Studies, Medicine, and Human Genetics; Comprehensive Cancer Center, University of Chicago, Chicago, Illinois; Department of Health Research and Policy, Stanford University School of Medicine; Stanford Cancer Institute, Stanford; Cancer Prevention Institute of California, Fremont; Department of Preventive Medicine, University of Southern California, Los Angeles; Stanford Cancer Institute, Palo Alto, California; Epidemiology and Genetics Research Program; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, New York; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix; Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, Arizona; Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg; Clinic of Gynaecology and Obstetrics, Division for Gynaecological Tumor-Genetics, Technische Universität München; Max Planck Institute of Psychiatry, Munich; Department of Obstetrics and Gynaecology, Division of Molecular Gynaeco-Oncology, PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne; Foundation for Quality and Efficiency in Health Care, Cologne; Department of Cancer Epidemiology/Clinical Cancer Registry; Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg; Department of Psychiatry, University of Mainz, Mainz, Germany; Samuel Lunenfeld Research Institute; Zane Cohen Cen

Abstract

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 may contain 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.

PMID:
24493630
PMCID:
PMC3990360
DOI:
10.1158/1055-9965.EPI-13-0340
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances, Grant support

Publication type

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center