{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T07:58:10Z","timestamp":1765612690984,"version":"3.48.0"},"reference-count":35,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[2012,1,6]]},"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Lynch syndrome is caused by germline mismatch repair (MMR) gene mutations. The PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      model predicts the likelihood of a MMR gene mutation based on personal and family cancer history.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To compare strategies using PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      and tumour testing (microsatellite instability (MSI) and\/or immunohistochemistry (IHC) staining) to identify mutation carriers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>\n                      Data from population-based or clinic-based patients with colorectal cancers enrolled through the Colon Cancer Family Registry were analysed. Evaluation included MSI, IHC and germline mutation analysis for\n                      <jats:italic>MLH1<\/jats:italic>\n                      ,\n                      <jats:italic>MSH2<\/jats:italic>\n                      ,\n                      <jats:italic>MSH6<\/jats:italic>\n                      and\n                      <jats:italic>PMS2<\/jats:italic>\n                      . Personal and family cancer histories were used to calculate PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      predictions. Discriminative ability to identify carriers from non-carriers using the area under the receiver operating characteristic curve (AUC) was assessed. Predictions were based on logistic regression models for (1) cancer assessment using PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      , (2) MSI, (3) IHC for loss of any MMR protein expression, (4) MSI+IHC, (5) PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      +MSI, (6) PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      +IHC, (7) PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      +IHC+MSI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 1651 subjects, 239 (14%) had mutations (90\n                      <jats:italic>MLH1<\/jats:italic>\n                      , 125\n                      <jats:italic>MSH2<\/jats:italic>\n                      , 24\n                      <jats:italic>MSH6<\/jats:italic>\n                      ). PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      discriminated well with AUC 0.90 (95% CI 0.88 to 0.92). MSI alone, IHC alone, or MSI+IHC each had lower AUCs: 0.77, 0.82 and 0.82, respectively. The added value of IHC+PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      was slightly greater than PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      +MSI (AUC 0.94 vs 0.93). Adding MSI to PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      +IHC did not improve discrimination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      and IHC showed excellent performance in distinguishing mutation carriers from non-carriers and performed best when combined. MSI may have a greater role in distinguishing Lynch syndrome from other familial colorectal cancer subtypes among cases with high PREMM\n                      <jats:sub>1,2,6<\/jats:sub>\n                      scores where genetic evaluation does not disclose a MMR mutation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2011-301265","type":"journal-article","created":{"date-parts":[[2012,2,16]],"date-time":"2012-02-16T20:34:03Z","timestamp":1329424443000},"page":"272-279","source":"Crossref","is-referenced-by-count":41,"title":["Comparison of the clinical prediction model PREMM\n                    <sub>1,2,6<\/sub>\n                    and molecular testing for the systematic identification of Lynch syndrome in colorectal cancer"],"prefix":"10.1136","volume":"62","author":[{"given":"Fay","family":"Kastrinos","sequence":"first","affiliation":[{"name":"Herbert Irving Comprehensive Cancer Center, Columbia University, Medical Center, New York, New York, USA"},{"name":"Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewout W","family":"Steyerberg","sequence":"additional","affiliation":[{"name":"Department of Public Health, Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Balma\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Vall d'Hebr\u00f3n, Medical Department of Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rowena","family":"Mercado","sequence":"additional","affiliation":[{"name":"Population Sciences Division, Dana-Farber Cancer Institute, Boston, Massachusetts, 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Public Health, University of Melbourne, Carlton, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loic","family":"LeMarchand","sequence":"additional","affiliation":[{"name":"Epidemiology Division, University of Hawaii Cancer Center, Honolulu, Hawaii, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noralane M","family":"Lindor","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Polly A","family":"Newcomb","sequence":"additional","affiliation":[{"name":"Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA"},{"name":"Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen 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