{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:24:37Z","timestamp":1787653477058,"version":"build-2736575974"},"reference-count":24,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Moscow Healthcare Department","award":["1022\/2"],"award-info":[{"award-number":["1022\/2"]}]},{"name":"Moscow Healthcare Department","award":["01-04-496"],"award-info":[{"award-number":["01-04-496"]}]},{"name":"Moscow Healthcare Department","award":["01-04-709"],"award-info":[{"award-number":["01-04-709"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>While pathogenic germline CHEK2 variants are known to increase cancer risk, there is currently insufficient evidence regarding the precise risk of developing malignant neoplasms associated with specific missense variants or variants of uncertain significance. As a result, no clear clinical guidelines exist regarding consultation, monitoring and specific treatment options for those patients. For the first time in Russia, clinical data and whole-genome sequencing (WGS) results were analyzed for 3150 patients with cancer and suspected hereditary cancer syndromes (HCS) and 5163 healthy individuals. This dataset formed the basis for assessing the role of germline CHEK2 variants in the development of different cancer types. The chromosomal coordinates and coding sequence coordinates are given in accordance with the GRCh38 (hg38) genome assembly and the NM_007194.4 transcript. Pathogenic (P) and likely pathogenic (LP) variants of CHEK2 significantly increased the risk of breast cancer (OR = 2.015 [95% CI: 1.27\u20133.21]; p = 0.0031), but the association with colorectal cancer was not statistically significant (OR = 1.354 [95% CI: 0.42\u20134.42]; p = 0.616). A moderate increase in cancer risk was identified for the c.1100del variant (OR = 2.263 [95% CI: 1.19\u20134.32]; p = 0.0132) and for the common P\/LP variants c.1100del, c.444+1G&gt;A and c.433C&gt;T (OR = 2.219 [95% CI: 1.40\u20133.51]; p = 0.0007). Notably, our study confirmed that CHEK2 c.470T&gt;C (p.Ile157Thr) is the most common variant in the patient group, identified in 3.8% of cases (120\/3150), compared with 3.0% in the control group (155\/5163). Although the association between the most common CHEK2 variant c.470T&gt;C and cancer risk reached nominal statistical significance (OR = 1.279 [95% CI: 1.00\u20131.63]; p = 0.0463), the effect size was minimal, suggesting that the contribution of this variant to hereditary cancer risk in the Russian population is modest. Additional studies are required before this variant can be definitively excluded from clinical interpretation.<\/jats:p>","DOI":"10.3390\/ijms27177602","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:04:55Z","timestamp":1787652295000},"page":"7602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CHEK2 Germline Variants in Cancer Predisposition: Whole Genome Sequencing Results"],"prefix":"10.3390","volume":"27","author":[{"given":"Marina V.","family":"Nemtsova","sequence":"first","affiliation":[{"name":"Evogen LLC, Fotiyevoy St., 6, b.1, 119333 Moscow, Russia"},{"name":"Research Centre for Medical Genetics, Moskvorechye St., 1, 115522 Moscow, Russia"},{"name":"Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov of the Ministry of Health of Russian Federation, Trubetskaya St., 8 p. 2, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1581-9118","authenticated-orcid":false,"given":"Maria V.","family":"Makarova","sequence":"additional","affiliation":[{"name":"Evogen LLC, Fotiyevoy St., 6, b.1, 119333 Moscow, Russia"},{"name":"Federal State Budgetary Institution Russian Scientific Center of Roentgenoradiology of the Ministry of Health of the Russian Federation, Profsoyuznaya St., 86, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia M.","family":"Danishevich","sequence":"additional","affiliation":[{"name":"Moscow Clinical Scientific Centre Named After A.S. Loginov, Novogireevskaya St., 1 p. 1, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M.","family":"Byakhova","sequence":"additional","affiliation":[{"name":"Moscow City Clinical Hospital Named After S.S. Yudin, Kolomensky pr., 4, 115446 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-4701","authenticated-orcid":false,"given":"Olesya S.","family":"Mishina","sequence":"additional","affiliation":[{"name":"Evogen LLC, Fotiyevoy St., 6, b.1, 119333 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alevtina E.","family":"Kiseleva","sequence":"additional","affiliation":[{"name":"Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov of the Ministry of Health of Russian Federation, Trubetskaya St., 8 p. 2, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim S.","family":"Belenikin","sequence":"additional","affiliation":[{"name":"Evogen LLC, Fotiyevoy St., 6, b.1, 119333 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia A.","family":"Krinitsina","sequence":"additional","affiliation":[{"name":"Evogen LLC, Fotiyevoy St., 6, b.1, 119333 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olesya V.","family":"Sagaydak","sequence":"additional","affiliation":[{"name":"Evogen LLC, Fotiyevoy St., 6, b.1, 119333 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna B.","family":"Semenova","sequence":"additional","affiliation":[{"name":"Moscow City Clinical Hospital Named After S.S. Yudin, Kolomensky pr., 4, 115446 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia A.","family":"Bodunova","sequence":"additional","affiliation":[{"name":"Moscow Clinical Scientific Centre Named After A.S. Loginov, Novogireevskaya St., 1 p. 1, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor E.","family":"Khatkov","sequence":"additional","affiliation":[{"name":"Moscow Clinical Scientific Centre Named After A.S. Loginov, Novogireevskaya St., 1 p. 1, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina A.","family":"Demidova","sequence":"additional","affiliation":[{"name":"Moscow City Oncology Hospital No. 62, Bolshoy Boulevard, 67, Skolkovo Innovation Center, 121205 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-7462","authenticated-orcid":false,"given":"Aleksey S.","family":"Tsukanov","sequence":"additional","affiliation":[{"name":"Ryzhikh National Medical Research Centre for Coloproctology, Salama Adil Str., 2, 123423 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vsevolod N.","family":"Galkin","sequence":"additional","affiliation":[{"name":"Moscow City Clinical Hospital Named After S.S. Yudin, Kolomensky pr., 4, 115446 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saida M.","family":"Gadzhyeva","sequence":"additional","affiliation":[{"name":"Moscow Healthcare Department, Oruzheyniy per., 43, 127006 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1007\/s12094-008-0248-5","article-title":"Role of CHK2 in cancer development","volume":"10","author":"Perona","year":"2008","journal-title":"Clin. Transl. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yamamoto, H., and Hirasawa, A. (2021). Homologous Recombination Deficiencies and Hereditary Tumors. Int. J. Mol. 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