The genotoxic damage generally refers to the chromatin or DNA damage, mainly including the gene mutations and chromosomal aberrations. A large number of reports have suggested that the cancer is associated with the gene mutations and chromosomal aberrations, and thus it has been a focus of research. Today new insights are proposed by analyzing relevant literature, suggesting that the cancer is not caused by the gene mutations and chromosomal aberrations, but by the regulatory dysfunction of gene expression resulted from the nuclear damage, among which, the gene mutations and chromosomal aberrations are only an accompany phenomena also resulting from the nuclear damage. The gene mutations generally do not cause diseases, but if they do, they mainly cause the single-gene diseases. The chromosomal aberrations usually refer to the abnormalities in chromosome structure and number, often leading to cell death or inducing various chromosomal diseases. Some chronic refractory diseases, such as the cancer, Alzheimer's disease, degenerative diseases, are probably not caused by the gene mutations and chromosomal abnormalities, but rather by the abnormal regulation of gene expression and the dysfunction of DNA transcription-protein synthesis resulted from the nuclear damage. These diseases are all the diseases of nuclear dysfunction and collapse of differentiation.