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We used a set of in silico predictions in combination with a STRING protein\u2013protein interaction and pathway analysis to identify the most likely variants predisposing to CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified Cell cycle\/DNA repair and TGF\u03b2 signaling\/Focal adhesion\/Extracellular matrix organization pathways as highly significant protein\u2013protein interaction networks. Variants in the\n                      <jats:italic>APCDD1<\/jats:italic>\n                      ,\n                      <jats:italic>CYBA<\/jats:italic>\n                      ,\n                      <jats:italic>PTK7<\/jats:italic>\n                      and\n                      <jats:italic>SRC<\/jats:italic>\n                      genes were identified in more than one family, and they were shown to dysregulate basic cellular functions, potentially leading to cancer development. Most variants were private to a family, and each family had more than one candidate variant, suggesting a synergistic or polygenic mode of inheritance. This hypothesis, as well as validation of the identified variants and pathways and their functional consequences, need confirmation by other family-based studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Different types of family-based analyses together with in silico predictions are helpful to identify candidate genes and pathways for CRC predisposition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40246-025-00901-y","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T17:22:56Z","timestamp":1767115376000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Familial colorectal cancer: search for novel predisposition genes"],"prefix":"10.1186","volume":"20","author":[{"given":"Asta","family":"F\u00f6rsti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beiping","family":"Miao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhishek","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmara","family":"Dymerska Zaremba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Marciniak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Lubinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kari","family":"Hemminki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"901_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13174385","author":"K Hemminki","year":"2021","unstructured":"Hemminki K, Sundquist K, Sundquist J, Forsti A, Hemminki A, Li X. 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