{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T09:52:35Z","timestamp":1777110755042,"version":"3.51.4"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2004,9,22]],"date-time":"2004-09-22T00:00:00Z","timestamp":1095811200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2004,9,22]],"date-time":"2004-09-22T00:00:00Z","timestamp":1095811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>The cell-cycle checkpoint kinase (CHEK)2 protein truncating mutation 1100delC has been associated with increased risk for breast or prostate cancer. Multiple studies have found an elevated frequency of the 1100delC variant in specific stratifications of breast cancer patients with a family history of the disease, including <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>BRCA2<\/jats:italic> negative families and families with a history of bilateral disease or male breast cancer. However, the 1100delC mutation has only been investigated in a few population-based studies and none from North America.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>We report here on the frequency of three <jats:italic>CHEK2<\/jats:italic> variants that alter protein function \u2013 1100delC, R145W, and I175T \u2013 in 506 cases and 459 controls from a population based, case\u2013control study of breast cancer conducted in young women from western Washington.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>There was a suggestive enrichment in the 1100delC variant in the cases (1.2%) as compared with the controls (0.4%), but this was based on small numbers of carriers and the differences were not statistically significant. The 1100delC variant was more frequent in cases with a first-degree family history of breast cancer (4.3%; <jats:italic>P<\/jats:italic> = 0.02) and slightly enriched in cases with a family history of ovarian cancer (4.4%; <jats:italic>P<\/jats:italic> = 0.09).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>The <jats:italic>CHEK2<\/jats:italic> variants are rare in the western Washington population and, based on accumulated evidence across studies, are unlikely to be major breast cancer susceptibility genes. Thus, screening for the 1100delC variant may have limited usefulness in breast cancer prevention programs in the USA.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr933","type":"journal-article","created":{"date-parts":[[2004,9,23]],"date-time":"2004-09-23T06:23:34Z","timestamp":1095920614000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Frequency of CHEK2 mutations in a population based, case\u2013control study of breast cancer in young women"],"prefix":"10.1186","volume":"6","author":[{"given":"Danielle M","family":"Friedrichsen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen E","family":"Malone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R","family":"Doody","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet R","family":"Daling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine A","family":"Ostrander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2004,9,22]]},"reference":[{"key":"932_CR1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1101\/gad.14.3.289","volume":"14","author":"SY Shieh","year":"2000","unstructured":"Shieh SY, Ahn J, Tamai K, Taya Y, Prives C: The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. 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