{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:41:22Z","timestamp":1788536482132,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19kk0305010"],"award-info":[{"award-number":["JP19kk0305010"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The application of advanced molecular technology has significantly expanded lymphoma classification, allowing risk stratification and treatment optimization. Limited evidence suggests the presence of a genetic predisposition in lymphoma, indicating the potential for better individualized clinical management based on a novel lymphoma classification. Herein, we examined the impact of germline pathogenic variants in 27 cancer\u2010predisposing genes with lymphoma risk and explored the clinical characteristics of pathogenic variant carriers. This study included 2,066 lymphoma patients and 38,153 cancer\u2010free controls from the Japanese population. Following quality control of sequencing data, samples from 1,982 lymphoma patients and 37,592 controls were further analyzed. We identified 309 pathogenic variants among 4,850 variants in the 27 cancer\u2010predisposing genes. Pathogenic variants in the following four cancer\u2010predisposing genes were associated with a high risk of lymphoma: <jats:italic>ATM<\/jats:italic> (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.25\u20135.51; <jats:italic>p<\/jats:italic>\u00a0=\u20091.06\u2009\u00d7\u200910<jats:sup>\u22122<\/jats:sup>), <jats:italic>BRCA1<\/jats:italic> (OR, 5.88; 95% CI, 2.65\u201313.02; <jats:italic>p<\/jats:italic>\u00a0=\u20091.27\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>), <jats:italic>BRCA2<\/jats:italic> (OR, 2.94; 95% CI, 1.60\u20135.42; <jats:italic>p<\/jats:italic>\u00a0=\u20095.25\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>), and <jats:italic>TP53<\/jats:italic> (OR, 5.22; 95% CI, 1.43\u201319.02; <jats:italic>p<\/jats:italic>\u00a0=\u20091.23\u2009\u00d7\u200910<jats:sup>\u22122<\/jats:sup>). The proportion of carriers of these genes was 1.6% of lymphoma patients. Furthermore, pathogenic variants in these genes were especially associated with a higher risk of mantle cell lymphoma (OR, 21.57; 95% CI, 7.59\u201361.26; <jats:italic>p<\/jats:italic>\u00a0=\u20098.07\u2009\u00d7\u200910<jats:sup>\u22129<\/jats:sup>). These results provide novel insights concerning monogenic form into lymphoma classification. Some lymphoma patients may benefit from surveillance and targeted treatment, such as other neoplasms.<\/jats:p>","DOI":"10.1111\/cas.15522","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T06:01:39Z","timestamp":1662444099000},"page":"3972-3979","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Association between germline pathogenic variants in cancer\u2010predisposing genes and lymphoma risk"],"prefix":"10.1111","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6180-0704","authenticated-orcid":false,"given":"Yoshiaki","family":"Usui","sequence":"first","affiliation":[{"name":"Laboratory for Genotyping Development RIKEN Center for Integrative Medical Sciences  Yokohama Japan"},{"name":"Department of Hematology, Oncology and Respiratory Medicine Okayama University Medical School  Okayama Japan"},{"name":"Division of Cancer Information and Control, Department of Preventive Medicine Aichi Cancer Center  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Laboratory for Genotyping Development RIKEN Center for Integrative Medical Sciences  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1761-6314","authenticated-orcid":false,"given":"Keitaro","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine Aichi Cancer Center  Nagoya Japan"},{"name":"Division of Cancer Epidemiology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikiko","family":"Endo","sequence":"additional","affiliation":[{"name":"Laboratory for Genotyping Development RIKEN Center for Integrative Medical Sciences  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Kamatani","sequence":"additional","affiliation":[{"name":"Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Services National Cancer Center Hospital  Tokyo Japan"},{"name":"Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kokichi","family":"Sugano","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Services National Cancer Center Hospital  Tokyo Japan"},{"name":"Department of Genetic Medicine Kyoundo Hospital, Sasaki Foundation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruhiko","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Services National Cancer Center Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2826-4396","authenticated-orcid":false,"given":"Yoshinori","family":"Murakami","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Respiratory Medicine Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1807-772X","authenticated-orcid":false,"given":"Hidewaki","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Laboratory for Cancer Genomics RIKEN Center for Integrative Medical Sciences  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5638-3504","authenticated-orcid":false,"given":"Yukihide","family":"Momozawa","sequence":"additional","affiliation":[{"name":"Laboratory for Genotyping Development RIKEN Center for Integrative Medical Sciences  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"International Agency for Research on Cancer.Cancer Today. 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