To investigate whether NTHL1-associated breast cancers are driven by the same mutagenesis mechanism as the colorectal cancers from carriers of homozygous mutations1,6, whole-genome sequencing was performed on the breast cancers from the NTHL1-null and NTHL1-het carriers of three different germlines LoF variants (p.(Gln90Ter), p.(Gln287Ter), and p.(Ser22AlafsTer5)), together with nine sporadic breast cancers with no known germline cancer predisposition gene mutations as controls. The gene discussed is NTHL1; the disease is cancer.