{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:11:47Z","timestamp":1791040307877,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,9,6]],"date-time":"2002-09-06T00:00:00Z","timestamp":1031270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2002,11,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of our study was to examine the role of genetic factors on early\u2010onset colorectal cancer after excluding the impact of germline mutations in the two major mismatch repair genes. A total of 131 incident probands, under 45 years at diagnosis of a first primary colorectal cancer selected from the Victorian Cancer Registry, and their first\u2010and second\u2010degree relatives, were interviewed. Germline DNA from all 12 probands with a family history meeting the modified Amsterdam Criteria for Hereditary Non\u2010Polyposis Colorectal Cancer (HNPCC) and a random sample of 31 of the remaining probands was screened for mutations in <jats:italic>hMSH2<\/jats:italic> and <jats:italic>hMLH1<\/jats:italic> via manual sequencing. Germline mutations were identified in 6 of the 131 probands (5%), all from the \u201cHNPCC\u201d families. Of the remaining 125 probands, 51 (41%) reported at least one first\u2010or second\u2010degree relative with colorectal cancer with an excess of colorectal cancer in first\u2010degree relatives (SMR = 2.7, 95% CI = 1.7\u20134.1, <jats:italic>p<\/jats:italic> &lt; 0.001). The lifetime risk to age 70 for first\u2010degree relatives was 8.0% (5.0\u201312.8%), compared to the Victorian population risk of 3.2% (<jats:italic>p<\/jats:italic> = 0.01). The best fitting major gene model was a recessively\u2010inherited risk of 98% to age 70 (95% CI = 24\u2013100%) carried by 0.17% of the population and would explain 15% of all colorectal cancer in cases with a diagnosis before age 45. Early\u2010onset colorectal cancer is strongly familial even after excluding families found to be segregating a mutation in either of the 2 major mismatch repair genes. There is evidence for a role of yet to be identified genes associated with a high recessively\u2010inherited risk of colorectal cancer. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10670","type":"journal-article","created":{"date-parts":[[2002,10,17]],"date-time":"2002-10-17T19:55:50Z","timestamp":1034884550000},"page":"166-171","source":"Crossref","is-referenced-by-count":44,"title":["After <i>hMSH2<\/i> and <i>hMLH1<\/i>\u2014what next? Analysis of three\u2010generational, population\u2010based, early\u2010onset colorectal cancer families"],"prefix":"10.1002","volume":"102","author":[{"given":"Mark A.","family":"Jenkins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Baglietto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian S.","family":"Dite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien J.","family":"Jolley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa C.","family":"Southey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Whitty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leeanne J.","family":"Mead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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