Germline DNA variations in breast cancer predisposition and prognosis: a systematic review of the literature.

Breast cancer is the most common cancer and the second leading cause of death in women worldwide. The disease is caused by a combination of genetic, environmental, lifestyle, and reproductive risk factors. Linkage and family-based studies have identified many pathological germline mutations, which account for around 20% of the genetic risk of familial breast cancer. In recent years, single nucleotide polymorphism-based genetic association studies, especially genome-wide association studies (GWASs), have been very successful in uncovering low-penetrance common variants associated with breast cancer risk. These common variants alone may explain up to an additional 30% of the familial risk of breast cancer. With the advent of available genetic resources and growing collaborations among researchers across the globe, the much needed large sample size to capture variants with small effect sizes and low population frequencies is being addressed, and hence many more common variants are expected to be discovered in the coming days. Here, major GWASs conducted for breast cancer predisposition and prognosis until 2013 are summarized. Few studies investigating other forms of genetic variations contributing to breast cancer predisposition and disease outcomes are also discussed. Finally, the potential utility of the GWAS-identified variants in disease risk models and some future perspectives are presented.