“Bad Luck Mutations”: DNA Mutations Are not the Whole Answer to Understanding Cancer Risk:

It has been proposed that many human cancers are generated by intrinsic mechanisms that produce “Bad Luck” mutations by the proliferation of organ-specific adult stem cells. There have been serious challenges to this interpretation, including multiple extrinsic factors thought to be correlated with mutations found in cancers associated with these exposures. While support for both interpretations provides some validity, both interpretations ignore several concepts of the multistage, multimechanism process of carcinogenesis, namely, (1) mutations can be generated by both “errors of DNA repair” and “errors of DNA replication,” during the “initiation” process of carcinogenesis; (2) “initiated” stem cells must be clonally amplified by nonmutagenic, intrinsic or extrinsic epigenetic mechanisms; (3) organ-specific stem cell numbers can be modified during in utero development, thereby altering the risk to cancer later in life; and (4) epigenetic tumor promoters are characterized by species, individual genetic-, g...