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Genome-wide linkage scan for breast cancer susceptibility loci in Swedish hereditary non-BRCA1/2 families: suggestive linkage to 10q23.32-q25.3.

Journal article
Authors Annika Bergman
Per Karlsson
Jonna Berggren
Tommy Martinsson
Karin Björck
Staffan Nilsson
Jan Wahlström
Arne Wallgren
Margareta Nordling
Published in Genes, chromosomes & cancer
Volume 46
Issue 3
Pages 302-9
ISSN 1045-2257
Publication year 2007
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Department of Mathematical Sciences, Mathematical Statistics
Institute of Clinical Sciences
Pages 302-9
Language en
Links dx.doi.org/10.1002/gcc.20405
Keywords Breast Neoplasms, genetics, Chromosomes, Human, Pair 10, genetics, European Continental Ancestry Group, Female, Genes, BRCA1, Genes, BRCA2, Genome, Human, Humans, Linkage (Genetics), Polymorphism, Single Nucleotide
Subject categories Medical and Health Sciences

Abstract

The two breast cancer genes BRCA1 and BRCA2 were identified more than 10 years ago and, depending on population, mutations in these genes are responsible for a varying percentage of familial breast cancer. In more than half the families, the increased risk of breast cancer cannot be explained by mutations in these genes, and the goal of this study was to locate novel susceptibility genes. One of the main difficulties in identifying the cause of hereditary non-BRCA1/BRCA2 breast cancer is genetic heterogeneity, possibly due to multiple, incompletely penetrant susceptibility genes, along with ethnic and geographic differences. In this study, one large family and 13 small to medium-sized families with multiple cases of breast cancer were analyzed by genome-wide linkage analysis. The genome scan was performed by genotype analysis of 10,000 SNP markers on microarrays. The strongest evidence of linkage (HLOD 2.34) was obtained on chromosome region 10q23.32-q25.3. A further two regions were identified, with LOD scores above 2.10 on 12q14-q21 and 19p13.3-q12. In a subset of families of western Swedish origin, two regions generated LOD scores exceeding 1.8: 10q23.32-q25.3 and 19q13.12-q13.32. The large family in the study exceeded LOD 1.5 in three regions: 10q23.32-q25.3, 19q13.12-q13.32, and 17p13. Our results indicate that one or more of the suggested regions may harbor genes that are involved in the development of breast cancer.

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