Familial concordance of breast cancer pathology as an indicator of genotype in multiple-case families

Balleine, Rosemary L., Provan, Pamela J., Pupo, Gulietta M., Pathmanathan, Nirmala, Cummings, Margaret, Farshid, Gelareh, Salisbury, Elizabeth L., Bilous, A. Michael, Byth, Karen and Mann, Graham J. (2010) Familial concordance of breast cancer pathology as an indicator of genotype in multiple-case families. Genes, Chromosomes and Cancer, 49 12: 1082-1094. doi:10.1002/gcc.20816

Author Balleine, Rosemary L.
Provan, Pamela J.
Pupo, Gulietta M.
Pathmanathan, Nirmala
Cummings, Margaret
Farshid, Gelareh
Salisbury, Elizabeth L.
Bilous, A. Michael
Byth, Karen
Mann, Graham J.
Title Familial concordance of breast cancer pathology as an indicator of genotype in multiple-case families
Journal name Genes, Chromosomes and Cancer   Check publisher's open access policy
ISSN 1045-2257
Publication date 2010-12
Sub-type Article (original research)
DOI 10.1002/gcc.20816
Volume 49
Issue 12
Start page 1082
End page 1094
Total pages 13
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2011
Language eng
Formatted abstract
The heterogeneity of multiple case breast cancer families that do not carry mutations in BRCA1 or BRCA2 (non-BRCA1/2 families) poses a challenge to the identification of breast cancer susceptibility genes. The aim of this study was to determine whether intrafamilial concordance in breast cancer pathology could identify subgroups of non-BRCA1/2 families with consistent genotypic features. Invasive breast cancers were reviewed from 84 individuals belonging to 30 multiple-case families; BRCA1 (n = 9), BRCA2 (n = 10), and non-BRCA1/2 (n = 11). Hierarchical cluster analysis based on histopathology and age at first diagnosis was then used to specify three subgroups designated Clusters 1–3. The genomic features of non-BRCA1/2 families were examined by genome wide linkage and FGFR2 SNP genotyping, according to whether they showed cluster-concordant or cluster-mixed familial pathology. The majority of pathogenic BRCA1 mutation carriers (80%) fell into a single cluster. In contrast pathogenic BRCA2 mutation carriers were distributed across all three clusters and within families, cluster groups were also generally mixed. Most non-BRCA1/2 mutation carriers belonged to Cluster 3 (71%). Genome wide linkage data from five non-BRCA1/2 Cluster 3-concordant families were compared with four mixed cluster non-BRCA1/2 families. This revealed a number of distinct linkage peaks, including some regions previously associated with breast cancer susceptibility. The distribution of low risk alleles in FGFR2 was not different between these two subgroups (P = 0.237). The pattern of breast cancer pathology concordance amongst family members may assist the investigation of breast cancer susceptibility in multiple case families. © 2010 Wiley-Liss, Inc.
Keyword Genome-wide association
Histopathological features
BRCA2 mutations
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
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Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 07 Nov 2010, 00:11:17 EST