## A predisposition to cancer can be inherited

Mutations in proto-oncogenes, tumour suppressor genes, and substances that ensure genome integrity can not only be acquired during life (through exposure to carcinogens or DNA replication errors) but in some cases can also be inherited from a parent through the germline. In this case, the affected individual has an increased risk of developing cancer during his or her lifetime, and this risk can also be passed on to his or her offspring if they inherit the mutant allele. An example of a familial form of cancer is retinoblastoma, which is caused by the loss of function of the tumour suppressor gene RB1. The standard tumour suppressor protein Rb prevents the cell from starting DNA replication and dividing under certain circumstances. Since mutations in the tumour suppressor gene have a recessive effect, both alleles must be mutated to trigger cancer development - this is then referred to as the need for two interventions: an inherited mutation turns off one allele, and a mutation acquired during life turns off the other. If mutations occur independently in all alleles of the gene during life, it is a sporadic occurrence of retinoblastoma (Figure 9.5), which is relatively rare and usually affects only one eye. However, there is also an inherited form of retinoblastoma, which is also one of the most common childhood cancers (Figure 9.5). The predisposition to retinoblastoma means that the mutated RB1 allele is inherited through the germline. When one allele is mutated, such patients are born with only one healthy allele. Although it is sufficient for a normal life, this means that a person with only one functional allele of the tumour suppressor Rb is more susceptible to environmental carcinogens, which may also cause mutation of the second allele. In the case of an inherited predisposition, not only one eye is usually affected, but both. An inherited predisposition to cancers can also be the cause of breast cancer, ovarian cancer, or colon and rectal cancer, for example.