Investigation of pathogenic variants in putative breast cancer predisposition genes in multiple case breast cancer families

New genes associated with risk of breast cancer continue to be discovered from large scale case-control studies. A recent large analysis identified four additional candidate predisposition genes (MAP3K1, LZTR1, ATRIP, CDKN2A). These genes had more protein-truncating and rare missense variants in women with breast cancer than were observed in matched unaffected women. This study will investigate multiple-case breast cancer families participating in the Australian Breast Cancer Family Study (ABCFS) that have an index case diagnosed with breast cancer under the age of 40 years and who have at least two other female relatives diagnosed with breast cancer under the age of 50 years. The prospective student will first investigate whole genome sequences of women from the multiple-case breast cancer families for pathogenic variants in bona fide breast cancer susceptibility genes (BRCA1, BRCA2, PALB2, ATM, CHEK2, and others). Families whose breast cancer risk is not explained by these genes will subsequently be investigated for variants in the newly identified candidate breast cancer susceptibility genes. Genetic variants will then be investigated for segregation within families by sequencing additional affected and unaffected relatives who have already provided blood samples to the ABCFS. This project will involve the sequencing and curation of genetic variants identified in research participants who have been diagnosed with breast cancer, providing an honours student with a foundational understanding of laboratory and computational genetics.