This paper illustrates the role of genetic risk assessment for hereditary breast cancer, using hereditary breast and ovarian cancer (HBOC) syndrome as a model due to germline mutations in the BRCA1 and BRCA2.
A polygenic model in which many individually weak genes combine multiplicately to cause a 50-fold range of risk in the population explains several puzzling aspects of familial breast cancer epidemiology, including the very high risk in some families and the failure to identify important new genes since the discovery of BRCA1 and BRCA2.
Referring to the case of genetic testing for hereditary breast cancer (and Myriad Genetics' patenting of the BRCA1 & BRCA2 genes), this paper applies some concepts from moral philosophy to think through the effects of the commercialisation of genetic technologies, and what would constitute a more just and rational approach to health care decision-making, in the context of the Canadian health insurance system.
These were models of Trp53-mutated breast cancer, Brca1- and Brca2-associated hereditary breast cancer, and E-cadherin (Cdh1) mutated lobular breast cancer.
It is well established that rare mutations in BRCA2 predispose to familial breast cancer, but whether common variants at this locus contribute more modest risk to sporadic breast cancer has not been thoroughly investigated.
Whether breast-feeding is associated with a reduced risk of hereditary breast cancer in women who carry deleterious BRCA1 and BRCA2 mutations is currently unknown.
This interest has been heightened by recent discoveries that germ-line mutations such as BRCA1 and BRCA2 in hereditary breast cancer are responsible for an increasing percentage of common solid tumors.
Recent studies on familial breast cancer clusters revealed chromosomal rearrangements and higher rates of sister chromatid exchanges also in heterozygous BRCA2 mutation carriers.
<b>Expert opinion</b>: The transition to multi-gene panels in breast cancer patients has improved the likelihood of capturing a rare variant in a well-established gene associated with hereditary breast cancer (e.g.<i>BRCA1 and BRCA2, TP53</i>).
This was a retrospective, hospital-based study of n = 99 archival breast tumors derived from women with a germline genetic BRCA1 or BRCA2 mutation and/or familial breast cancer history.
The role of the familial breast cancer susceptibility genes, BRCA1 and BRCA2, in the homologous recombination (HR) pathway for DNA double-strand break (DSB) repair suggests that the mechanisms involved in HR and DNA DSB repair are of etiological importance during breast tumorigenesis.
We found that 20 index patients (2.4%) in the FBC group carried a BRCA1 or BRCA2 LGR, and the frequencies of BRCA1 and BRCA2 LGRs were 1.6% and 0.8%, respectively.
Subgroup analyses observed prevalences of the BRCA mutation as follows: 19.6 % among patients with BC family history only (BRCA1 7.6 % and BRCA2 12.0 %) and 36.6 % among patients with OC family history only (BRCA1 21.5 % and BRCA2 15.1 %).
In this study, we analyzed a "variant of uncertain significance" (VUS) located in exon 23 of the BRCA2 gene exhibited by six members of five distinct families with hereditary breast cancer (BC).