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The search for the role of primary genetic factors was heralded by studies at the infrahuman level, particularly on laboratory mouse strains with strong susceptibility to carcinogen\u2010induced cancer, and conversely, with resistance to the same carcinogens. These studies, developed in the 19th and 20th centuries, continue today. This article traces the historical aspects of hereditary cancer dealing with identification and ultimate molecular genetic confirmation of commonly occurring cancers, particularly of the colon in the case of familial adenomatous polyposis and its attenuated form, both due to the\n                    <jats:italic>APC<\/jats:italic>\n                    germline mutation; the Lynch syndrome due to mutations in mismatch repair genes, the most common of which were found to be\n                    <jats:italic>MSH2<\/jats:italic>\n                    ,\n                    <jats:italic>MLH1<\/jats:italic>\n                    , and\n                    <jats:italic>MSH6<\/jats:italic>\n                    germline mutations; the hereditary breast\u2010ovarian cancer syndrome with\n                    <jats:italic>BRCA1<\/jats:italic>\n                    and\n                    <jats:italic>BRCA2<\/jats:italic>\n                    germline mutations; the Li\u2010Fraumeni (SBLA) syndrome due to the\n                    <jats:italic>p53<\/jats:italic>\n                    mutation; and the familial atypical multiple mole melanoma in association with pancreatic cancer due to the\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    (\n                    <jats:italic>p16<\/jats:italic>\n                    ) germline mutation. These and other hereditary cancer syndromes have been discussed in some detail relevant to their characterization, which, for many conditions, took place in the late 18th century and, in the more modern molecular genetic era, during the past two decades. Emphasis has been placed upon the manner in which improved cancer control will emanate from these discoveries. \u00a9 2004 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.c.30026","type":"journal-article","created":{"date-parts":[[2004,7,6]],"date-time":"2004-07-06T13:01:26Z","timestamp":1089118886000},"page":"5-22","source":"Crossref","is-referenced-by-count":48,"title":["Inherited predisposition to cancer: A historical overview"],"prefix":"10.1002","volume":"129C","author":[{"given":"Henry T.","family":"Lynch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trudy G.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane 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