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

• 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. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

BRCA1 protein

BRCA2 protein

article

breast cancer

cancer genetics

cancer research

cancer susceptibility

chromosome 10q

chromosome 12q

chromosome 17p

chromosome 19p

chromosome 19q

clinical article

ethnicity

female

gene identification

gene mutation

genetic heterogeneity

genetic linkage

genetic susceptibility

genome analysis

genotype

geographic distribution

heredity

human

marker gene

microarray analysis

oncogene

population genetics

priority journal

single nucleotide polymorphism

Sweden

tumor suppressor gene

Breast Neoplasms

Chromosomes

Human

Pair 10

European Continental Ancestry Group

Genes

BRCA1

Genes

BRCA2

Genome

Human

Humans

Linkage (Genetics)

Polymorphism

Single Nucleotide

Breast Neoplasms

genetics

Chromosomes

Human

Pair 10

European Continental Ancestry Group

Female

Genes

BRCA1

BRCA2

Genome

Humans

Linkage (Genetics)

Polymorphism

Single Nucleotide

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)