{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:48:54Z","timestamp":1789829334208,"version":"4.0.1"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T00:00:00Z","timestamp":1556150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9lius Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010711","name":"Cancer Foundation Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,11,15]]},"abstract":"<jats:p>\n                    Mutations in\n                    <jats:italic>BRCA1<\/jats:italic>\n                    and\n                    <jats:italic>BRCA2<\/jats:italic>\n                    genes predispose to breast and ovarian cancer (BC\/OC) with a high lifetime risk, whereas mutations in\n                    <jats:italic>PALB2<\/jats:italic>\n                    ,\n                    <jats:italic>CHEK2<\/jats:italic>\n                    ,\n                    <jats:italic>ATM<\/jats:italic>\n                    ,\n                    <jats:italic>FANCM<\/jats:italic>\n                    ,\n                    <jats:italic>RAD51C<\/jats:italic>\n                    and\n                    <jats:italic>RAD51D<\/jats:italic>\n                    genes cause a moderately elevated risk. In the Finnish population, recurrent mutations have been identified in all of these genes, the latest being\n                    <jats:italic>CHEK2<\/jats:italic>\n                    c.319+2T&gt;A and c.444+1G&gt;A. By genotyping 3,156 cases and 2,089 controls, we estimated the frequencies of\n                    <jats:italic>CHEK2<\/jats:italic>\n                    c.319+2T&gt;A and c.444+1G&gt;A in Finnish BC patients.\n                    <jats:italic>CHEK2<\/jats:italic>\n                    c.319+2T&gt;A was detected in 0.7% of the patients, and it was associated with a high risk of BC in the unselected patient group (OR\u2009= 5.40 [95% CI 1.58\u201318.45],\n                    <jats:italic>p<\/jats:italic>\n                    = 0.007) and similarly in the familial patient group.\n                    <jats:italic>CHEK2<\/jats:italic>\n                    c.444+1G&gt;A was identified in 0.1% of all patients. Additionally, we evaluated the combined prevalence of recurrent moderate\u2010risk gene mutations in 2,487 BC patients, 556 OC patients and 261\n                    <jats:italic>BRCA1\/2<\/jats:italic>\n                    carriers from 109 families. The overall frequency of the mutations was 13.3% in 1,141\n                    <jats:italic>BRCA1\/2<\/jats:italic>\n                    \u2010negative familial BC patients, 7.5% in 1,727 unselected BC patients and 7.2% in 556 unselected OC patients. At least one moderate\u2010risk gene mutation was found in 12.5% of\n                    <jats:italic>BRCA1<\/jats:italic>\n                    families and 7.1% of\n                    <jats:italic>BRCA1<\/jats:italic>\n                    index patients, as well as in 17.0% of\n                    <jats:italic>BRCA2<\/jats:italic>\n                    families and 11.3% of\n                    <jats:italic>BRCA2<\/jats:italic>\n                    index patients, and the mutations were associated with an additional risk in the\n                    <jats:italic>BRCA1\/2<\/jats:italic>\n                    index patients (OR\u2009= 2.63 [1.15\u20135.48],\n                    <jats:italic>p<\/jats:italic>\n                    = 0.011). These results support gene panel testing of even multiple members of BC families where several mutations may segregate in different individuals.\n                  <\/jats:p>","DOI":"10.1002\/ijc.32309","type":"journal-article","created":{"date-parts":[[2019,3,30]],"date-time":"2019-03-30T04:53:20Z","timestamp":1553921600000},"page":"2692-2700","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Recurrent moderate\u2010risk mutations in Finnish breast and ovarian cancer patients"],"prefix":"10.1002","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0479-0711","authenticated-orcid":false,"given":"Anna","family":"Nurmi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taru A.","family":"Muranen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liisa M.","family":"Pelttari","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna I.","family":"Kiiski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomas","family":"Heikkinen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Helsinki and Helsinki University Hospital  Helsinki 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