{"entity": "publication", "iuid": "567f1e445eab4cdc987f086685d0350b", "timestamp": "2026-04-20T03:45:41.500Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/567f1e445eab4cdc987f086685d0350b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/567f1e445eab4cdc987f086685d0350b"}}, "title": "A search for modifying genetic factors in CHEK2:c.1100delC breast cancer patients.", "authors": [{"family": "Wendt", "given": "Camilla", "initials": "C"}, {"family": "Muranen", "given": "Taru A", "initials": "TA"}, {"family": "Mielik\u00e4inen", "given": "Lotta", "initials": "L"}, {"family": "Thutkawkorapin", "given": "Jessada", "initials": "J"}, {"family": "Blomqvist", "given": "Carl", "initials": "C"}, {"family": "Jiao", "given": "Xiang", "initials": "X"}, {"family": "Ehrencrona", "given": "Hans", "initials": "H"}, {"family": "Tham", "given": "Emma", "initials": "E"}, {"family": "Arver", "given": "Brita", "initials": "B"}, {"family": "Melin", "given": "Beatrice", "initials": "B"}, {"family": "Kuchinskaya", "given": "Ekaterina", "initials": "E"}, {"family": "Stenmark Askmalm", "given": "Marie", "initials": "M"}, {"family": "Paulsson-Karlsson", "given": "Ylva", "initials": "Y"}, {"family": "Einbeigi", "given": "Zakaria", "initials": "Z"}, {"family": "von Wachenfeldt V\u00e4ppling", "given": "Anna", "initials": "A"}, {"family": "Kalso", "given": "Eija", "initials": "E"}, {"family": "Tasmuth", "given": "Tiina", "initials": "T"}, {"family": "Kallioniemi", "given": "Anne", "initials": "A"}, {"family": "Aittom\u00e4ki", "given": "Kristiina", "initials": "K"}, {"family": "Nevanlinna", "given": "Heli", "initials": "H"}, {"family": "Borg", "given": "\u00c5ke", "initials": "\u00c5"}, {"family": "Lindblom", "given": "Annika", "initials": "A"}], "type": "journal article", "published": "2021-07-20", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "11", "issue": "1", "pages": "14763", "issn-l": "2045-2322"}, "abstract": "The risk of breast cancer associated with CHEK2:c.1100delC is 2-threefold but higher in carriers with a family history of breast cancer than without, suggesting that other genetic loci in combination with CHEK2:c.1100delC confer an increased risk in a polygenic model. Part of the excess familial risk has been associated with common low-penetrance variants. This study aimed to identify genetic loci that modify CHEK2:c.1100delC-associated breast cancer risk by searching for candidate risk alleles that are overrepresented in CHEK2:c.1100delC carriers with breast cancer compared with controls. We performed whole-exome sequencing in 28 breast cancer cases with germline CHEK2: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 CHEK2: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 CHEK2:c.1100delC cases compared with familial breast cancer, sporadic breast cancer and controls. With this method, we found no support for a CHEK2:c.1100delC-specific genetic modifier. Further studies of CHEK2:c.1100delC genetic modifiers are warranted to improve risk assessment in clinical practice.", "doi": "10.1038/s41598-021-93926-x", "pmid": "34285278", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-021-93926-x"}, {"db": "pmc", "key": "PMC8292481"}], "notes": [], "created": "2021-09-13T06:42:16.025Z", "modified": "2024-01-16T13:48:39.103Z"}