Exploration of the postponing mechanism that delays carcinoma onset.

The average age at onset of malignancies arising from epithelial tissues is between 40 and 70 years old even in familial cancers. Although it is believed that the accumulation of multiple genetic alterations is needed for cancer onset, we hypothesize--based on the diversity of ages at onset for most types of epithelial cancer--that there is a postponing mechanism inside the human body that significantly delays the process of carcinogenesis. The key molecules controlling the cancer onset, here called "postponers", are hypothesized to be functioning in the individuals carrying susceptibility genes. As a consequence, cancers occur in middle age or even old age, with several decades of cancer-free lifetime for the patient. Genome-wide association studies and genomic expression profiling are suggested to identify candidate postponers. Hypothetic gene expression patterns for identifying candidate postponers are illustrated. Animal models will be helpful to test whether the absence or presence of the postponer molecules can alter the onset age of spontaneous tumors. If this hypothesis is true, by amplification of the postponing mechanism we might be able to significantly delay the onset of tumors, so that individuals carrying cancer susceptibility traits could gain an additional significant period of cancer-free life. Moreover, destructive prophylactic surgeries, e.g., for women who have BRCA1/2 gene mutations, might be avoided.