{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T01:33:04Z","timestamp":1768008784935,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,12,15]],"date-time":"2008-12-15T00:00:00Z","timestamp":1229299200000},"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":[[2009,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Approximately 1\u20132% of colorectal cancers (CRC) arise because of germline mutations in DNA mismatch repair genes, referred to as Lynch syndrome. These tumours show microsatellite instability (MSI) and loss of expression of mismatch repair proteins. Pre\u2010symptomatic identification of mutation carriers has been demonstrated to improve survival; however, there is concern that many are not being identified using current practices. We evaluated population\u2010based MSI screening of CRC in young patients as a means of ascertaining mutation carriers. CRC diagnosed in patients aged &lt;60 years were identified from pathology records. No prior information was available on family history of cancer. PCR techniques were used to determine MSI in the BAT\u201026 mononucleotide repeat and mutation in the <jats:italic>BRAF<\/jats:italic> oncogene. Loss of MLH1, MSH2, MSH6 and PMS2 protein expression was evaluated in MSI+ tumours by immunohistochemistry. MSI+ tumours were found in 105\/1,344 (7.8%) patients, of which 7 were excluded as possible Lynch syndrome because of <jats:italic>BRAF<\/jats:italic> mutation. Of the 98 \u201cred flag\u201d cases that were followed up, 25 were already known as mutation carriers or members of mutation carrier families. Germline test results were obtained for 35 patients and revealed that 22 showed no apparent mutation, 11 showed likely pathogenic mutations and 2 had unclassified variants. The proportion of MSI+ cases in different age groups that were estimated to be mutation carriers was 89% (&lt;30 years), 83% (30\u201339), 68% (40\u201349) and 17% (50\u201359). We recommend MSI as the initial test for population\u2010based screening of Lynch syndrome in younger CRC patients, regardless of family history. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23863","type":"journal-article","created":{"date-parts":[[2008,12,17]],"date-time":"2008-12-17T00:55:02Z","timestamp":1229475302000},"page":"1097-1102","source":"Crossref","is-referenced-by-count":63,"title":["Population\u2010based detection of Lynch syndrome in young colorectal cancer patients using microsatellite instability as the initial test"],"prefix":"10.1002","volume":"124","author":[{"given":"Lyn","family":"Schofield","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha","family":"Watson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabienne","family":"Grieu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei Qi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nik","family":"Zeps","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennet","family":"Harvey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Abdo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Goldblatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Iacopetta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,12,15]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199805213382101"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra012242"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/363558a0"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/0031302021000035965-2"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2007.060162"},{"key":"e_1_2_6_7_2","first-page":"808","article-title":"Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair\u2010defective human tumor cell lines","volume":"57","author":"Kane MF","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-1118-3"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.020651"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70168-5"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19980501)82:9<1632::AID-CNCR6>3.0.CO;2-C"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70510-X"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djh034"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11912"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastro.2005.06.033"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2004.00220.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.671"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-3565(04)00352-0"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.16.1986"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-5994.2007.01470.x"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043146"},{"key":"e_1_2_6_22_2","unstructured":"ThrelfallT ThompsonJ. 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