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How many genes contribute to the susceptibility or resistance to neoplasia in human beings? The answer has implications for clinical cancer management, genetic counseling, and research into the origins and pathogenesis of specific cancers. One of the oldest catalogs of human disease genes, McKusick’s Mendelian Inheritance in Man (MIM), has an up-to-date on-line version, OMIM (www.ncbi.nlm.nih.gov/Omim/Omim). As of 15 February 2000, OMIM contained 11,201 entries, 11–14 % of the estimated number of human genes. By reading the hard copy volume of MIM and the periodic literature, as well as an extensive electronic search of OMIM and PUBMED from the US National Library of Medicine, it was concluded that, in 1999, 635 entries related to neoplasia (5.7 % of known human genes, 0.6 to 0.8 % of the total genome). About two-thirds of the traits are phenotypes, mostly clinical syndromes that predispose to or are complicated by malignant or benign neoplasia, such as neurofibromatosis, cystic fibrosis, and Cowden disease. These traits should be sought in a patient presenting which a specific tumor as a clue to etiology since they may represent germline mutations that have implications for genetic counseling of the patient’s family. About one-third of the entries are protooncogenes, tumor suppressor genes, translocation breakpoints, fusion proteins, and other markers that have been seen to date only as somatic cell mutations, largely in sporadic tumors and cell lines. They may eventually be shown to have germline mutations but, in any case, contribute to pathogenesis of specific sporadic tumors. Since human cancer genes are recognized by the occurrence of disease when the normal allele is mutated, the photographic image is the maximal repertory of genes that contribute to resistance to cancer. Search of OMIM can yield a quick estimate of the upper limit of the number of genes contributing to specific tumors, for example breast cancer has 157 entries, colon cancer 118, pheochromocytoma 39, and pancreatic cancer 67. |
