Abstract ES1-1: Management of non-BRCA breast cancer predisposition

In the years since the discovery of BRCA1 and BRCA2, researchers have extended our understanding of the genetic architecture of breast cancer risk. Breast cancer has been described as a component tumor or a number of high penetrance autosomal dominant predisposition syndromes, such as Li-Fraumeni, Cowden Syndrome, Hereditary Diffuse Gastric Cancer, Peutz-Jeghers Syndrome, and possibly Lynch Syndrome. These are rare, but have clear clinical relevance once identified. At the other end of the spectrum, a series of genome-wide association studies (GWAS) identified over 80 common variants (SNPs) associated with breast cancer risk in the general population. The risk of an individual SNP is very low. An individual inheriting a significant number of risk alleles, however, may be a a clinically relevant degree of risk, even without a family history. An individual polygenic risk score can be calculated and correlates with risk, although how to apply this clinically is uncertain. Lastly, mutations in a number of moderate penetrance genes have been found that confer average relative risks of 2-3, with even higher risks in the setting of a family history. These genes include CHEK2, ATM, PALB2, and possibly others such as NBN. Other genes such as BARD1 and MRE11A have also been suggested to be moderate penetrance predisposition genes, but evidence of clinical validity is lacking. None of these are clearly linked to ovarian cancer risk. Genes such as BRIP1 and RAD51B/C/D appear to be modera...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Invited Speaker Abstracts Source Type: research