Statistics from Altmetric.com
- ESE, exonic splicing enhancer
- HA, heteroduplex analysis
- PTT, protein truncation test
- SNP, single nucleotide polymorphism
Breast cancer is a leading cause of cancer deaths among women, and is expected to claim the lives of nearly 40 000 individuals in the USA each year (American Cancer Society Breast Cancer Facts and Figures 2003–2004). Only 5–10% of breast cancers are associated with mutations in the susceptibility genes BRCA1 and BRCA2. However, in cases associated with strong family history, mutation rates are higher, ranging from 16% to 26% for BRCA11–3 and from 7% to 13% for BRCA2.2,3 However, many breast cancer patients with strong family histories have no obvious mutations in BRCA1/2. While there is an active search for other breast cancer susceptibility genes, it is possible that the true contributions of BRCA1 and BRCA2 to early onset breast cancer have been underestimated. Indeed, one study has shown that only 63% of breast cancer families linked to BRCA1 are associated with detectable mutations in BRCA1.4 Several reasons for this discrepancy are possible. For example, mutations in BRCA1 promoter sequences might be undetectable by current detection techniques. Additionally, inherited genomic rearrangements that inactivate BRCA1 and BRCA2 but cannot be detected by conventional polymerase chain reaction (PCR) based assays have been reported.5,6,7,8,9,10 Finally, it is possible that some genetic variants previously dismissed as “unclassified variants” or “polymorphisms” may have hitherto underappreciated effects on protein synthesis or function.
Most studies of BRCA1 and BRCA2 associated breast cancers have focused on white populations, yet several observations suggest that there might be a genetic component to breast cancer susceptibility in families of African ancestry.11 Breast cancer is less common in African populations than in other populations but, when it does occur, it is characterised by an early age of onset and a higher mortality.12–14 Additionally, …