{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:31:56Z","timestamp":1792621916637,"version":"4.5.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["22K07266"],"award-info":[{"award-number":["22K07266"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Lynch syndrome (LS) is a genetic condition characterized by an increased risk of colorectal cancer and other associated malignancies. With the limited information available regarding extracolonic tumours, this study aimed to explore tumours associated with LS in the Japanese population and discuss the potential differences in causative pathogenic genetic variants and their phenotypic expression compared with Western cohorts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This multicentre retrospective cohort study analysed 316 genetically confirmed LS cases (148 men and 168 women) from 13 institutions. We analysed the incidence of extracolonic LS-associated tumours according to sex and gene variants, including MLH1 (124 cases), MSH2 (139), MSH6 (37), PMS2 (11), and EPCAM (5). Extracolonic tumour types assessed included 88 endometrial, 47 gastric, 27 small intestinal, 21 urothelial, 13 ovarian, 8 biliary tract, 5 brain, three pancreatic, and 18 other cancers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The cumulative risk by age 70 was 66% for endometrial cancer, 23% for gastric cancer, 14% for small intestine cancer, 10% for upper urothelial cancer, 9% for ovarian cancer, and 3% for biliary tract cancer. The mean age at diagnosis varied, with gastric and small intestinal cancers presenting later in life than urothelial, endometrial, and ovarian cancers. Men had a higher risk of most cancers, except for gynaecological cancers. Gastric and urothelial cancers were primarily associated with MLH1 and MSH2 pathogenic variants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study highlights the need for tailored surveillance programmes based on cancer type, sex, causative pathogenic genetic variants, and risk profiles to effectively manage LS in Japan.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jjco\/hyaf087","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T08:03:52Z","timestamp":1746777832000},"page":"1005-1012","source":"Crossref","is-referenced-by-count":3,"title":["Risks of extracolonic tumours in patients with Lynch syndrome: a nationwide multicentre cohort study in Japan"],"prefix":"10.1093","volume":"55","author":[{"given":"Fumitaka","family":"Taniguchi","sequence":"first","affiliation":[{"name":"Department of Surgery, National Hospital Organization Iwakuni Clinical Center , 1-1-1 Atago-machi, Iwakuni City, Yamaguchi Prefecture 740-8510 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohji","family":"Tanakaya","sequence":"additional","affiliation":[{"name":"Department of Surgery, National Hospital Organization Iwakuni Clinical Center , 1-1-1 Atago-machi, Iwakuni City, Yamaguchi Prefecture 740-8510 ,","place":["Japan"]},{"name":"The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum , 2 Sanbancho, Chiyoda Ward, Tokyo 102-0075 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Chino","sequence":"additional","affiliation":[{"name":"The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum , 2 Sanbancho, Chiyoda Ward, Tokyo 102-0075 ,","place":["Japan"]},{"name":"Department of Gastroenterology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research , 3-8-31 Ariake, Koto Ward, Tokyo 135-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum , 2 Sanbancho, Chiyoda Ward, Tokyo 102-0075 ,","place":["Japan"]},{"name":"Department of Genetic Oncology, Osaka Prefectural Hospital Organization Osaka International Cancer Institute , 3-1-69 Otemae, Chuo Ward, Osaka City, Osaka Prefecture 541-8567 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arisa","family":"Ueki","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Cancer Institute Hospital of the Japanese Foundation for Cancer Research , 3-8-31 Ariake, Koto Ward, Tokyo 135-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuki","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research , 3-8-31 Ariake, Koto Ward, Tokyo 135-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiki","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Surgery, National Hospital Organization Iwakuni Clinical Center , 1-1-1 Atago-machi, Iwakuni City, Yamaguchi Prefecture 740-8510 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiwamu","family":"Akagi","sequence":"additional","affiliation":[{"name":"The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum , 2 Sanbancho, Chiyoda Ward, Tokyo 102-0075 ,","place":["Japan"]},{"name":"Department of Molecular Diagnosis and Cancer Prevention, Saitama Prefectural Cancer Center , 780 Komuro, Ina Town, Kitaadachi District, Saitama Prefecture 362-0806 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gou","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum , 2 Sanbancho, Chiyoda Ward, Tokyo 102-0075 ,","place":["Japan"]},{"name":"Department of Molecular Diagnosis and Cancer Prevention, Saitama Prefectural Cancer Center , 780 Komuro, Ina Town, Kitaadachi District, Saitama Prefecture 362-0806 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinari","family":"Takao","sequence":"additional","affiliation":[{"name":"The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum , 2 Sanbancho, Chiyoda Ward, Tokyo 102-0075 ,","place":["Japan"]},{"name":"Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital , 3-18-22 Honkomagome, Bunkyo Ward, Tokyo 113-8677 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misato","family":"Takao","sequence":"additional","affiliation":[{"name":"Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital , 3-18-22 Honkomagome, Bunkyo Ward, Tokyo 113-8677 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Yamada","sequence":"additional","affiliation":[{"name":"The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum , 2 Sanbancho, Chiyoda Ward, Tokyo 102-0075 ,","place":["Japan"]},{"name":"Endoscopy Division, National Cancer Center Hospital , 5-1-1 Tsukiji, Chuo Ward, Tokyo 104-0045 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai Ego","family":"Makiguchi","sequence":"additional","affiliation":[{"name":"Endoscopy Division, National Cancer Center Hospital , 5-1-1 Tsukiji, Chuo Ward, Tokyo 104-0045 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Ishida","sequence":"additional","affiliation":[{"name":"The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum , 2 Sanbancho, Chiyoda Ward, Tokyo 102-0075 ,","place":["Japan"]},{"name":"Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University , 1981 Kamoda, Kawagoe City, Saitama Prefecture 350-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University , 1981 Kamoda, Kawagoe City, Saitama Prefecture 350-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Miguchi","sequence":"additional","affiliation":[{"name":"The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum , 2 Sanbancho, Chiyoda Ward, Tokyo 102-0075 ,","place":["Japan"]},{"name":"Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital , 1-5-54 Ujina-Kanda, Minami Ward, Hiroshima City, Hiroshima Prefecture 734-8530 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Hirata","sequence":"additional","affiliation":[{"name":"The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum , 2 Sanbancho, Chiyoda Ward, Tokyo 102-0075 ,","place":["Japan"]},{"name":"Department of Surgery 1, University of Occupational and Environmental Health , 1-1 Isegatake, Yahatanishi Ward, Kitakyushu City, Fukuoka Prefecture 807-8556 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum , 2 Sanbancho, Chiyoda Ward, Tokyo 102-0075 ,","place":["Japan"]},{"name":"Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital , 3-18-22 Honkomagome, Bunkyo Ward, Tokyo 113-8677 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiro","family":"Tomita","sequence":"additional","affiliation":[{"name":"The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum , 2 Sanbancho, Chiyoda Ward, Tokyo 102-0075 ,","place":["Japan"]},{"name":"Cancer Treatment Center, Toyonaka Municipal Hospital , 4-14-1 Shibahara Town, Toyonaka City, Osaka Prefecture 560-8565 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