In particular, signature 1 and signature 5 arise in all cancer types and most cancer samples, signature 3 is strongly associated with the epigenetic silencing of RAD51C and BRCA1 by promoter methylation in breast cancer, and signature 2 and signature 13 are associated with the activities of the APOBEC machinery, contributing to susceptibility to breast cancer [54]. Here, BRCA1 is linked to cancer.