{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:32:54Z","timestamp":1787063574386,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2025,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    While cervical cancer is associated with a persistent human papillomavirus (HPV) infection, the progression to cancer is influenced by genomic risk factors that have remained largely obscure. Pathogenic variants in genes of the homology\u2010directed repair (HDR) or mismatch repair (MMR) are known to predispose to diverse tumour entities including breast and ovarian cancer (HDR) or colon and endometrial cancer (MMR). We here investigate the spectrum of HDR and MMR germline variants in cervical cancer, with particular focus on the HPV status and histological subgroups. We performed targeted next\u2010generation sequencing for 5\u2009MMR genes and 12 HDR genes on 728 German patients with cervical dysplasia or invasive cancer. In total, 4% of our patients carried a pathogenic germline variant, based on ClinVar classifications and additional ESM1b and AlphaMissense predictions. These included 15 patients with truncating variants in HDR genes (\n                    <jats:italic>BARD1<\/jats:italic>\n                    ,\n                    <jats:italic>BRCA1<\/jats:italic>\n                    ,\n                    <jats:italic>BRCA2<\/jats:italic>\n                    ,\n                    <jats:italic>BRIP1<\/jats:italic>\n                    ,\n                    <jats:italic>FANCM<\/jats:italic>\n                    ,\n                    <jats:italic>RAD51D<\/jats:italic>\n                    and\n                    <jats:italic>SLX4<\/jats:italic>\n                    ). MMR\u2010related gene variants were less prevalent and mainly of the missense type. While MMR\u2010related gene variants tended to associate with adenocarcinomas, HDR gene variants were commonly observed in squamous cancers. While one patient with HPV\u2010negative cancer carried a pathogenic MMR gene variant (in\n                    <jats:italic>MSH6<\/jats:italic>\n                    ), the HDR germline variants were found in patients with HPV\u2010positive cancers and tended to associate with HPV18. Taken together, our study supports a potentially risk\u2010modifying role of MMR and HDR germline variants in cervical cancer but no association with HPV\u2010negative status. These variants may be exploitable in future therapeutic managements.\n                  <\/jats:p>","DOI":"10.1002\/ijc.35221","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T07:13:33Z","timestamp":1729667613000},"page":"700-710","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Germline variants of homology\u2010directed repair or mismatch repair genes in cervical cancer"],"prefix":"10.1002","volume":"156","author":[{"given":"Lara","family":"Kokem\u00fcller","sequence":"first","affiliation":[{"name":"Department of Gynaecology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8139-7799","authenticated-orcid":false,"given":"Dhanya","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Hannover Medical School  Hannover 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