Cancer heritable syndromes

As in cancer predisposing syndromes, these genetic alterations are sometimes carried in the germline. Among human tumours, heritable mutations are an exception. Most alterations are acquired in somatic life in the form of chromosomal translocations, deletions, inversions, amplifications or point mutations. Certain oncogenic viruses play important roles in a few human tumours. Examples are human papilloma-virus in cervical cancer and skin tumours, Ep-stein-Barr virus in nasopharyngeal carcinoma and Burkitt s lymphoma, and human T-cell leukaemia viruses (e.g. HTLV-I, HTLV-II) in T-cell leukaemia. 

Finally, we consider physiological expression or suppression, and the long latent period between carcinogen treatment and tumor appearance. While it makes sense to think in terms of phenotypic lag, clonal growth, vascularization, immuno-suppression, and other phenomena, we just do not know enough today to define clear-cut experimental approaches. However, at the human level, the undesirable endpoints of this series of processes are clear teratologic syndromes, cancer, and heritable birth defects. 

Mutations in p53 occur in spontaneous and inherited cancers. The role of pS3 in DNA repair appears to be to momentarily halt the progression of the cell cycle, so PS to give various DNA repair enzymes a chance to complete their job, prior to initiation of DNA synthesis. Oi craJI, p53 is mutated in about half of all human cancers. Li-Fraumenj syndrome is a rare type of cancer that involves an ir herited mulabon in p5.3. About 50% of the affected persons acquire cancer by the age of 30 (Harvey et ai-, 15 95). 

Infrequently, the critical alteration in gene function may be transmitted to an individual from a parent through the germ fine, in which case the mutation can result in a familial (heritable) cancer syndrome, such as retinoblastoma or one of the multiple endocrine neoplasias. 

Within a population there is a proportion of individuals who are predisposed to develop cancer, either as an apparently sporadic disease or in response to an environmental challenge, such as exposure to tobacco smoke or ionising radiation. The abnormally high frequency of some tumor types within related members of large famihes provided evidence that cancer is, in some circumstances, a heritable disease. Genetic linkage studies of these famihes has revealed that a number of these cancer syndromes occur as simple Mendelian traits, usuaUy with a highly penetrant dominant pattern of inheritance. 

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