Hello Rohit Rajan

Children are born with mutation in the Rb gene that they inherit from one of their parents or this gene change may happen during the very early stages of their development in the womb. Each cell normally has two Rb genes. As long as a retinal cell has at least one Rb gene that works as it should, it will not form a retinoblastoma. But when both of the Rb genes are mutated or missing, a cell can grow unchecked. This can lead to further gene changes, which in turn may cause cells to become cancerous.

On the other hand, p53 gene follows a different pattern in carcinogenesis. It may be mutated during life time when the body is exposed to cancer-causing substances in the environment (carcinogens) such as tobacco smoke, other toxic chemicals, ultraviolet light, radiation, etc. Somatic mutations in p53 gene are one of the most frequent alterations in human cancers, and germline mutations are the underlying cause of Li-Fraumeni syndrome, which predisposes to a wide spectrum of early-onset cancers.

A number of environmental mutagens have been identified that react with a specific set of DNA sequences which are found in the TP53 gene. As such they could contribute to an enhanced frequency of specific p53 mutant alleles. It is common that these mutagens further show tissue specificity for the cancers they promote and that enhances the evidence for a role by these mutagens. Changes in mutant p53 proteins, produces loss of function (DNA binding and transcription) or some mutant proteins have an allele-specific gain of function that promotes cancer.

Best.