Surveying germline genomic landscape of breast cancer

The recent large genotyping studies have identified a new repertoire of breast cancer susceptibility genes and loci which are characterized by common risk alleles and low relative risks. Because of these properties, these loci explain a much larger proportion of the etiology of the particular cancers, described by the population attributable fraction (PAF), than of their familial risks. PAF is particularly suitable for ‘genomic landscaping’ because it defines the proportion of breast cancer explained by the variant under study. The joint PAF for the previously described high-penetrance alleles is about 1%, for moderate-penetrance alleles it is 1.5% and for low-penetrance susceptibility alleles it is 58%. The evidence appears compelling in pointing to the remarkably high population impacts of the recently described heritable loci compared to the ‘classical’ high-penetrance genes.