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Part of the excess familial risk has been associated with common low-penetrance variants. This study aimed to identify genetic loci that modify <jats:italic>CHEK2<\/jats:italic>:c.1100delC-associated breast cancer risk by searching for candidate risk alleles that are overrepresented in <jats:italic>CHEK2<\/jats:italic>:c.1100delC carriers with breast cancer compared with controls. We performed whole-exome sequencing in 28 breast cancer cases with germline <jats:italic>CHEK2<\/jats:italic>:c.1100delC, 28 familial breast cancer cases and 70 controls. Candidate alleles were selected for validation in larger cohorts. One recessive synonymous variant, rs16897117, was suggested, but no overrepresentation of homozygous <jats:italic>CHEK2<\/jats:italic>:c.1100delC carriers was found in the following validation. Furthermore, 11 non-synonymous candidate alleles were suggested for further testing, but no significant difference in allele frequency could be detected in the validation in <jats:italic>CHEK2<\/jats:italic>:c.1100delC cases compared with familial breast cancer, sporadic breast cancer and controls. With this method, we found no support for a <jats:italic>CHEK2<\/jats:italic>:c.1100delC-specific genetic modifier. Further studies of <jats:italic>CHEK2<\/jats:italic>:c.1100delC genetic modifiers are warranted to improve risk assessment in clinical practice.<\/jats:p>","DOI":"10.1038\/s41598-021-93926-x","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T10:26:57Z","timestamp":1626776817000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A search for modifying genetic factors in CHEK2:c.1100delC breast cancer patients"],"prefix":"10.1038","volume":"11","author":[{"given":"Camilla","family":"Wendt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taru A.","family":"Muranen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lotta","family":"Mielik\u00e4inen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessada","family":"Thutkawkorapin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl","family":"Blomqvist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Ehrencrona","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Tham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brita","family":"Arver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Melin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Kuchinskaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Stenmark Askmalm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ylva","family":"Paulsson-Karlsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zakaria","family":"Einbeigi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"von Wachenfeldt V\u00e4ppling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eija","family":"Kalso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiina","family":"Tasmuth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Kallioniemi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristiina","family":"Aittom\u00e4ki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heli","family":"Nevanlinna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c5ke","family":"Borg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika","family":"Lindblom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"issue":"7","key":"93926_CR1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1136\/jmg.2007.056556","volume":"45","author":"AC Antoniou","year":"2008","unstructured":"Antoniou, A. 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