caa a22 4500 445860987 CHVBK 20180317145442.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00439-011-0973-1 doi (NATIONALLICENCE)springer-10.1007/s00439-011-0973-1 Potential novel candidate polymorphisms identified in genome-wide association study for breast cancer susceptibility [Elektronische Daten] [Badan Sehrawat, Malinee Sridharan, Sunita Ghosh, Paula Robson, Carol Cass, John Mackey, Russell Greiner, Sambasivarao Damaraju] Previous genome-wide association studies (GWAS) have shown several risk alleles to be associated with breast cancer. However, the variants identified so far contribute to only a small proportion of disease risk. The objective of our GWAS was to identify additional novel breast cancer susceptibility variants and to replicate these findings in an independent cohort. We performed a two-stage association study in a cohort of 3,064 women from Alberta, Canada. In Stage I, we interrogated 906,600 single nucleotide polymorphisms (SNPs) on Affymetrix SNP 6.0 arrays using 348 breast cancer cases and 348 controls. We used single-locus association tests to determine statistical significance for the observed differences in allele frequencies between cases and controls. In Stage II, we attempted to replicate 35 significant markers identified in Stage I in an independent study of 1,153 cases and 1,215 controls. Genotyping of Stage II samples was done using Sequenom Mass-ARRAY iPlex platform. Six loci from four different gene regions (chromosomes 4, 5, 16 and 19) showed statistically significant differences between cases and controls in both Stage I and Stage II testing, and also in joint analysis. The identified variants were from EDNRA, ROPN1L, C16orf61 and ZNF577 gene regions. The presented joint analyses from the two-stage study design were not significant after genome-wide correction. The SNPs identified in this study may serve as potential candidate loci for breast cancer risk in a further replication study in Stage III from Alberta population or independent validation in Caucasian cohorts elsewhere. The Author(s), 2011 Sehrawat Badan Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada aut Sridharan Malinee Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada aut Ghosh Sunita Department of Experimental Oncology, Cross Cancer Institute, Edmonton, AB, Canada aut Robson Paula Department of Population Health, University of Alberta, Edmonton, AB, Canada aut Cass Carol Department of Experimental Oncology, Cross Cancer Institute, Edmonton, AB, Canada aut Mackey John Department of Experimental Oncology, Cross Cancer Institute, Edmonton, AB, Canada aut Greiner Russell PolyomX Program, Alberta Health Services, Cross Cancer Institute, Edmonton, AB, Canada aut Damaraju Sambasivarao Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada aut Human Genetics Springer-Verlag 130/4(2011-10-01), 529-537 0340-6717 130:4<529 2011 130 439 https://doi.org/10.1007/s00439-011-0973-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-0973-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sehrawat Badan Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada aut NATIONALLICENCE 700 1- Sridharan Malinee Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada aut NATIONALLICENCE 700 1- Ghosh Sunita Department of Experimental Oncology, Cross Cancer Institute, Edmonton, AB, Canada aut NATIONALLICENCE 700 1- Robson Paula Department of Population Health, University of Alberta, Edmonton, AB, Canada aut NATIONALLICENCE 700 1- Cass Carol Department of Experimental Oncology, Cross Cancer Institute, Edmonton, AB, Canada aut NATIONALLICENCE 700 1- Mackey John Department of Experimental Oncology, Cross Cancer Institute, Edmonton, AB, Canada aut NATIONALLICENCE 700 1- Greiner Russell PolyomX Program, Alberta Health Services, Cross Cancer Institute, Edmonton, AB, Canada aut NATIONALLICENCE 700 1- Damaraju Sambasivarao Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 130/4(2011-10-01), 529-537 0340-6717 130:4<529 2011 130 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer