The value of large international consortia in characterizing genetic susceptibility to breast cancer

It has long been recognized that having a close relative with the disease is one of the strongest risk factors for developing breast cancer. Many studies over the last two decades have focused on identifying the specific genetic and environmental factors responsible for this familial clustering. Initially these methods were linkage analysis in large high-risk families followed by positional cloning (responsible for the discovery of BRCA1 and BRCA2) and then in the last decade has seen Genome-Wide Association (GWAS) studies and most recently, whole exome and whole genome sequencing. Given that the initial discoveries were of the most common effects associated with the largest effect sizes, the discovery of additional loci implicated in contributing to the familial risk of breast cancer requires very large sample sizes and thus is most suitable to international collaboration. In this presentation, I will describe the progress that has been made in identifying such loci/genes and describe a number of ongoing international collaborations/consortia that have been instrumental in these successes. These include the iCOGS and OncoArray efforts, the BCAC consortium, COMPELXO and ENIGMA consortia and the IBCCS study. In addition I will describe some collaborations geared towards looking at the effects of life-style factors in modifying risks conferred by genetic predisposition. Other consortia have been focusing on interpretation of the large amount of sequence variants discovered through both research-based and clinical sequencing of known breast cancer genetic predisposition genes. Lastly, I will describe means by which additional progress can be made in our understanding of the familial component of breast cancer.