{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T21:42:50Z","timestamp":1760305370843,"version":"build-2065373602"},"reference-count":29,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Several recurring pathogenic variants in <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>BRCA2<\/jats:italic> and other cancer susceptibility genes are encountered in ethnically diverse Jewish populations. The yield of genotyping for these recurring pathogenic variants in healthy Israeli individuals unselected for ethnicity, sex, or a family history of cancer has not been previously reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Individuals voluntarily participating in annual medical surveillance at the Institute of Medical Screening of Sheba Medical Center were offered genotyping for predominant pathogenic variants in <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>BRCA2<\/jats:italic> and recurring variants in <jats:italic>CHEK2<\/jats:italic>, <jats:italic>MUTYH<\/jats:italic>, <jats:italic>APC<\/jats:italic>, and the Lynch syndrome genes via a chip\u2010based assay at the oncogenetic service of Sheba Medical Center from May 15, 2018, to December 15, 2020. All study participants were unrelated to one another. The study was approved by the Sheba ethics committee.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 1764 individuals, including 1008 females (57%), with a mean age of 54.2 years (range, 25\u201086 years) were genotyped. The yield of the testing was 4% (71 of 1764), and it was higher in Ashkenazi Jews (AJs) and mixed AJ\u2013non\u2010AJ participants (4.75% [58 of 1222]; 1.8% for <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>BRCA2<\/jats:italic> pathogenic variants) than non\u2010AJ patients (2.2% [9 of 401]; 1% for <jats:italic>BRCA1<\/jats:italic> pathogenic variants). When <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>BRCA2<\/jats:italic> pathogenic variants were excluded, 2.44% carried low\u2010penetrance variants, including <jats:italic>CHEK2<\/jats:italic> c.1283C&gt;T (n = 3), <jats:italic>APC<\/jats:italic> c.3920T&gt;A (n = 36), and heterozygous <jats:italic>MUTYH<\/jats:italic> c.1187G&gt;A (n = 4). A family history of cancer was not associated with a higher yield of pathogenic variant detection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The observed rates of positive genotyping in a healthy, unselected, multiethnic Israeli population warrant consideration of the inclusion of targeted genotyping of selected pathogenic variants in high\u2010penetrance and perhaps lower penetrance cancer susceptibility genes for all Jewish individuals in Israel, regardless of their ethnicity or family history of cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33560","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T19:08:35Z","timestamp":1624388915000},"page":"3599-3604","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Yield of targeted genotyping for the recurring pathogenic variants in cancer susceptibility genes in a healthy, multiethnic Israeli population"],"prefix":"10.1002","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4068-9514","authenticated-orcid":false,"given":"Rinat","family":"Bernstein\u2010Molho","sequence":"first","affiliation":[{"name":"Sackler School of Medicine Tel\u2010Aviv University Tel\u2010Aviv Israel"},{"name":"Breast Cancer Unit Oncology Institute Chaim Sheba Medical Center Tel\u2010Hashomer Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Galmor","sequence":"additional","affiliation":[{"name":"Sackler School of Medicine Tel\u2010Aviv University Tel\u2010Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yael","family":"Laitman","sequence":"additional","affiliation":[{"name":"Oncogenetics Unit, Institute of Genetics Chaim Sheba Medical Center Tel\u2010Hashomer Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shlomo","family":"Segev","sequence":"additional","affiliation":[{"name":"Sackler School of Medicine Tel\u2010Aviv University Tel\u2010Aviv Israel"},{"name":"Institute of Medical Screening Chaim Sheba Medical Center Tel\u2010Hashomer Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6745-1733","authenticated-orcid":false,"given":"Eitan","family":"Friedman","sequence":"additional","affiliation":[{"name":"Sackler School of Medicine Tel\u2010Aviv University Tel\u2010Aviv Israel"},{"name":"Oncogenetics Unit, Institute of Genetics Chaim Sheba Medical Center Tel\u2010Hashomer 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