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We screened 71 patients with MPC of the stomach, colorectal, and endometrium, sequencing 65 cancer predisposition genes. A subset of 19 patients with early-onset MPC of stomach and colorectum were further evaluated for variants in cancer related genes using both normal and tumor whole exome sequencing. Among 71 patients with MPCs, variants classified to be pathogenic were observed in 15 (21.1%) patients and affected Lynch Syndrome (LS) genes:\n                    <jats:italic>MLH1<\/jats:italic>\n                    (n\u2009=\u200910),\n                    <jats:italic>MSH6<\/jats:italic>\n                    (n\u2009=\u20092),\n                    <jats:italic>PMS2<\/jats:italic>\n                    (n\u2009=\u20092), and\n                    <jats:italic>MSH2<\/jats:italic>\n                    (n\u2009=\u20091). All carriers had tumors with high microsatellite instability and 13 of them (86.7%) were early-onset, consistent with LS. In 19 patients with early-onset MPCs, loss of function (LoF) variants in\n                    <jats:italic>RECQL5<\/jats:italic>\n                    were more prevalent in non-LS MPC than in matched sporadic cancer patients (OR\u2009=\u200931.6, 2.73\u20131700.6,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001). Additionally, there were high-confidence LoF variants at\n                    <jats:italic>FANCG<\/jats:italic>\n                    and\n                    <jats:italic>CASP8<\/jats:italic>\n                    in two patients accompanied by somatic loss of heterozygosity in tumor, respectively. The results suggest that genetic screening should be considered for synchronous cancers and metachronous MPCs of the LS tumor spectrum, particularly in early-onset. Susceptibility variants in non-LS genes for MPC patients may exist, but evidence for their role is more elusive than for LS patients.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-94292-4","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T06:26:57Z","timestamp":1626762417000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Prevalence of cancer susceptibility variants in patients with multiple Lynch syndrome related cancers"],"prefix":"10.1038","volume":"11","author":[{"given":"Yoon Young","family":"Choi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su-Jin","family":"Shin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Eun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Madlensky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Tae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Soo","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong-Hyeon","family":"Jo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunki","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Nachmanson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Hoon","family":"Noh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Ho","family":"Cheong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Harismendy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"key":"94292_CR1","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/nature12981","volume":"505","author":"N Rahman","year":"2014","unstructured":"Rahman, N. 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