| Title: |
Familial concordance of breast cancer pathology as an indicator of genotype in multiple-case families |
| Authors: |
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. |
| Publisher Information: |
John Wiley & Sons |
| Publication Year: |
2010 |
| Collection: |
The University of Queensland: UQ eSpace |
| Subject Terms: |
Genome-wide association; Histopathological features; Estrogen-receptor; BRCA2 mutations; 1306 Cancer Research; 1311 Genetics |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1045-2257; 1098-2264 |
| Availability: |
https://espace.library.uq.edu.au/view/UQ:219960 |
| Accession Number: |
edsbas.1BC87438 |
| Database: |
BASE |