{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:06:32Z","timestamp":1760148392578,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Moscow Healthcare Department"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>More than 275 million people in the world are carriers of a heterozygous mutation of the CFTR gene, associated with cystic fibrosis, the most common autosomal recessive disease among Caucasians. Some recent studies assessed the association between carriers of CFTR variants and some pathologies, including cancer risk. The aim of this study is to analyze the landscape of germline pathogenic heterozygous CFTR variants in patients with diagnosed malignant neoplasms. For the first time in Russia, we evaluated the frequency of CFTR pathogenic variants by whole-genome sequencing in 1800 patients with cancer and compared this with frequencies of CFTR variants in the control group (1825 people) adjusted for age and 10,000 healthy individuals. In the issue, 47 out of 1800 patients (2.6%) were carriers of CFTR pathogenic genetic variants: 0.028 (42\/1525) (2.8%) among breast cancer patients, 0.017 (3\/181) (1.7%) among colorectal cancer patients and 0.021 (2\/94) (2.1%) among ovarian cancer patients. Pathogenic CFTR variants were found in 52\/1825 cases (2.85%) in the control group and 221 (2.21%) in 10,000 healthy individuals. Based on the results of the comparison, there was no significant difference in the frequency and distribution of pathogenic variants of the CFTR gene, which is probably due to the study limitations. Obviously, additional studies are needed to assess the clinical significance of the heterozygous carriage of CFTR pathogenic variants in the development of various pathologies in the future, particularly cancer.<\/jats:p>","DOI":"10.3390\/ijms24097940","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T02:27:56Z","timestamp":1682648876000},"page":"7940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The CFTR Gene Germline Heterozygous Pathogenic Variants in Russian Patients with Malignant Neoplasms and Healthy Carriers: 11,800 WGS Results"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1581-9118","authenticated-orcid":false,"given":"Maria","family":"Makarova","sequence":"first","affiliation":[{"name":"LLC Evogen, 115191 Moscow, Russia"},{"name":"Federal State Budgetary Institution Russian Scientific Center of Roentgenoradiology of the Ministry of Healthcare of the Russian Federation, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Nemtsova","sequence":"additional","affiliation":[{"name":"LLC Evogen, 115191 Moscow, Russia"},{"name":"Research Centre for Medical Genetics of N.P. Bochkov, 115522 Moscow, Russia"},{"name":"Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov of the Ministry of Health of Russian Federation, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasiia","family":"Danishevich","sequence":"additional","affiliation":[{"name":"SBHI Moscow Clinical Scientific Center Named after Loginov MHD, 111123 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Chernevskiy","sequence":"additional","affiliation":[{"name":"LLC Evogen, 115191 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxim","family":"Belenikin","sequence":"additional","affiliation":[{"name":"LLC Evogen, 115191 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasiia","family":"Krinitsina","sequence":"additional","affiliation":[{"name":"LLC Evogen, 115191 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Baranova","sequence":"additional","affiliation":[{"name":"LLC Evogen, 115191 Moscow, Russia"},{"name":"Academy of Continuing Professional Education of the Ministry of Health of Russian Federation, 125993 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olesya","family":"Sagaydak","sequence":"additional","affiliation":[{"name":"LLC Evogen, 115191 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Vorontsova","sequence":"additional","affiliation":[{"name":"The National Medical Research Center for Endocrinology, 117292 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Khatkov","sequence":"additional","affiliation":[{"name":"SBHI Moscow Clinical Scientific Center Named after Loginov MHD, 111123 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4848-6938","authenticated-orcid":false,"given":"Lyudmila","family":"Zhukova","sequence":"additional","affiliation":[{"name":"SBHI Moscow Clinical Scientific Center Named after Loginov MHD, 111123 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Bodunova","sequence":"additional","affiliation":[{"name":"SBHI Moscow Clinical Scientific Center Named after Loginov MHD, 111123 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Nikolaev","sequence":"additional","affiliation":[{"name":"SBHI Moscow Clinical Scientific Center Named after Loginov MHD, 111123 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariya","family":"Byakhova","sequence":"additional","affiliation":[{"name":"City Clinical Oncological Hospital No. 1, Moscow Department of Healthcare, 117152 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Semenova","sequence":"additional","affiliation":[{"name":"City Clinical Oncological Hospital No. 1, Moscow Department of Healthcare, 117152 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vsevolod","family":"Galkin","sequence":"additional","affiliation":[{"name":"City Clinical Oncological Hospital No. 1, Moscow Department of Healthcare, 117152 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saida","family":"Gadzhieva","sequence":"additional","affiliation":[{"name":"City Clinical Oncological Hospital No. 1, Moscow Department of Healthcare, 117152 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5732","DOI":"10.3748\/wjg.v25.i38.5732","article-title":"Role of ion channels in gastrointestinal cancer","volume":"25","author":"Anderson","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Scott, P., Anderson, K., Singhania, M., and Cormier, R. (2020). Cystic Fibrosis, CFTR, and Colorectal Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082891"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bhattacharya, R., Blankenheim, Z., Scott, P.M., and Cormier, R.T. (2022). CFTR and Gastrointestinal Cancers: An Update. J. Pers. Med., 12.","DOI":"10.3390\/jpm12060868"},{"key":"ref_4","unstructured":"(2023, March 06). Cystic Fibrosis Foundation. Available online: https:\/\/www.cff.org."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1093\/jnci\/djs481","article-title":"Cancer risk in cystic fibrosis: A 20-year nationwide study from the United States","volume":"105","author":"Maisonneuve","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S1470-2045(18)30188-8","article-title":"Risk of gastrointestinal cancers in patients with cystic fibrosis: A systematic review and meta-analysis","volume":"19","author":"Yamada","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Soares de Lima, Y., Arnau-Collell, C., D\u00edaz-Gay, M., Bonjoch, L., Franch-Exp\u00f3sito, S., Mu\u00f1oz, J., Moreira, L., Oca\u00f1a, T., Cuatrecasas, M., and Herrera-Pariente, C. (2021). Germline and Somatic Whole-Exome Sequencing Identifies New Candidate Genes Involved in Familial Predisposition to Serrated Polyposis Syndrome. Cancers, 13.","DOI":"10.3390\/cancers13040929"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1002\/ijc.33431","article-title":"Cystic fibrosis F508del carriers and cancer risk: Results from the UK Biobank","volume":"148","author":"Shi","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1053\/j.gastro.2017.12.012","article-title":"Cystic Fibrosis Colorectal Cancer Screening Task Force (2018). Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations","volume":"154","author":"Hadjiliadis","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00018-016-2393-9","article-title":"Cystic fibrosis: A clinical view","volume":"74","author":"Castellani","year":"2017","journal-title":"Cell. Mol. Life. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1073\/pnas.1914912117","article-title":"Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions","volume":"117","author":"Miller","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","unstructured":"Federal Service For Surveillance in Healthcare (2023, March 15). Registration Certificate for a Medical Device RZN 2020\/13100, Available online: https:\/\/nevacert.ru\/reestry\/med-reestr\/rzn-2020-13100-47207\/maket."},{"key":"ref_13","first-page":"679","article-title":"Cystic Fibrosis Polymorphic Variants in a Russian Population","volume":"13","author":"Kiseleva","year":"2020","journal-title":"Pharmgenomics Pers. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.bbrc.2019.01.100","article-title":"CFTR constrains the dierentiation from mouse embryonic stem cells to intestine lineage cells","volume":"510","author":"Li","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1093\/hmg\/ddab206","article-title":"WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas","volume":"30","author":"Aavikko","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1097\/MPA.0000000000001136","article-title":"Germline Variants and Risk for Pancreatic Cancer: A Systematic Review and Emerging Concepts","volume":"47","author":"Zhan","year":"2018","journal-title":"Pancreas"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.chest.2016.08.1242","article-title":"Cancer Risks in Heterozygous Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) DelF508 Carriers","volume":"150","author":"Sugunaraj","year":"2016","journal-title":"Chest"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E226","DOI":"10.25011\/cim.v37i4.21728","article-title":"Predictive value of cystic fibrosis transmembrane conductance regulator (CFTR) in the diagnosis of gastric cancer","volume":"37","author":"Liu","year":"2014","journal-title":"Clin. Investig. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4179","DOI":"10.1038\/onc.2015.483","article-title":"CFTR is a tumor suppressor gene in murine and human intestinal cancer","volume":"35","author":"Than","year":"2016","journal-title":"Oncogene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1056\/NEJMra072067","article-title":"Epigenetics in cancer","volume":"58","author":"Esteller","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/cbin.11260","article-title":"Promoter hypermethylation of the CFTR gene as a novel diagnostic and prognostic marker of breast cancer","volume":"44","author":"Liu","year":"2020","journal-title":"Cell Biol. Int."},{"key":"ref_22","unstructured":"(2023, March 06). Genome Aggregation Database. Available online: https:\/\/gnomad.broadinstitute.org."},{"key":"ref_23","unstructured":"(2023, March 06). An Online Catalog of Human Genes and Genetic Disorders. Available online: https:\/\/omim.org."},{"key":"ref_24","unstructured":"(2023, March 06). Cancer Genome Interpreter. Available online: https:\/\/www.cancergenomeinterpreter.org\/home."},{"key":"ref_25","unstructured":"(2023, March 06). My Cancer Genome. Available online: https:\/\/www.mycancergenome.org."},{"key":"ref_26","unstructured":"(2023, March 06). National Center for Biotechnology Information, Available online: https:\/\/www.ncbi.nlm.nih.gov."},{"key":"ref_27","unstructured":"(2023, March 06). The Human Genomics Community. Available online: https:\/\/varsome.com."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1002\/humu.23276","article-title":"CFTR-France, a national relational patient database for sharing genetic and phenotypic data associated with rare CFTR variants","volume":"38","author":"Claustres","year":"2017","journal-title":"Hum. 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