The ninth Gordon Hamilton-Fairley memorial lecture: Hereditary cancers: clues to mechanisms of carcinogenesis

Abstract

The study of hereditary cancer in humans, notably retinoblastoma, has identified a category of cancer genes that is different from that of the oncogenes. Whereas the latter group of genes exerts its effect through expression, the former does so as a result of failure of normal expression. Primary oncogene abnormality seems to play a crucial initiating role in certain neoplasms, particularly leukaemias, lymphomas and some sarcomas. In contrast, anti-oncogenes (tumour suppressor genes) appear to be important in the initiation of several solid tumours of children, as well as some common carcinomas of adults. Both classes are apparently involved in tumour progression and metastasis. Virtually every kind of cancer can occur in hereditary form, so the role of anti-oncogenes in the origin of human cancers may be considerable. The prototypic anti-oncogene has been that for retinoblastoma. For this tumour the recessive mechanism has been demonstrated by molecular means, and the gene has been cloned. The possibility has been suggested that gene (or gene product) replacement therapy could be accomplished.

The causes and prevention of cancer.

“…Overall cancer rates increase exponentially with age except for a blip on the curve for childhood cancer, which is thought to be mainly due to inheriting a mutant cancer gene (141,142). Heredity is likely to affect susceptibility to all cancers, but to what extent is not clear, though it is obvious that skin color plays a large role in sun-associated cancers such as melanoma.…”

Molecular Pathology of Non-Small-Cell Lung Cancer

“…TSGs are believed to be inactivated in a two-step process involving both alleles. LOH by chromosomal deletion or translocation is usually one step, while the second copy of the gene is altered by point mutation [25]. However, epigenetic changes such as hypermethylation and homozygous deletion may also contribute to the loss of TSG function.…”

Thymoma and Multiple Malignancies: A Case of Five Synchronous Neoplasms and Literature Review

“…Treatment itself was not found to be an independent risk for second cancers, supporting the notion of an inherent predisposition to neoplasia in patients with Hodgkin's disease. Well-studied inherited mutations such as p53 (Li-Fraumeni syndrome), 31 mismatch-repair genes in Lynch syndromes 32 and Rb protein (p105-RB), in retinoblastoma, 33 …”