Samenvatting

5% to 10% of all cancers are linked to gene mutations inherited from parents. The most common gene related to hereditary cancer is the p53 gene. It is a crucial tumor suppressor. However, the mutated gene is commonly inherited from one generation to another one. The functions of p53 resume to the activation when there are stress signals such as DNA damage, oncogene activation, etc. As a tumor suppressor, the p53 gene has 3 major functions: Cell cycle arrest, DNA damage repair, and Apoptosis.
However, impairment or loss of p53 function can occur either by missense mutation, increased expression of negative regulators, or alterations in upstream/downstream pathways. A specific feature of mutant p53 is its gain-of-function (GOF) that promotes tumorigenesis. Hence, the inheritance of a TP53 mutation causes a predisposition to early-onset cancers. The most known inherited predisposition to a wide range of cancers due to the mutated p53 gene is Li-Fraumeni syndrome(LFS). In this review, it is discussed the role of inherited p53 gene mutations in the development of different cancers. However, research is still in progress on the inherited p53 predisposition and why some people with the inherited p53 gene have a higher risk to develop cancer. There is still no specific guideline for a variant of the germline TP53 gene.