DNA damage appears to be the primary underlying cause of cancer, and deficiencies in DNA repair likely underlie many forms of cancer. If DNA repair is deficient, DNA damage tends to accumulate. Such excess DNA damage may increase mutational errors during DNA replication due to error-prone translesion synthesis. Excess DNA damage may also increase epigenetic alterations due to errors during DNA repair. Such mutations and epigenetic alterations may give rise to cancer. The frequent epigenetic deficiency of ATM in a number of cancers likely contributed to the progression of those cancers.