{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:41:57Z","timestamp":1792021317634,"version":"4.4.0"},"reference-count":91,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Science and Technology in Oncogenomics","award":["FAPESP 2008\/57887\u20139"],"award-info":[{"award-number":["FAPESP 2008\/57887\u20139"]}]},{"name":"National Institute of Science and Technology in Oncogenomics","award":["CNPq 573589\/08\u20139"],"award-info":[{"award-number":["CNPq 573589\/08\u20139"]}]},{"name":"Danish Colorectal Cancer Center South","award":["FAPESP 2008\/57887\u20139"],"award-info":[{"award-number":["FAPESP 2008\/57887\u20139"]}]},{"name":"Danish Colorectal Cancer Center South","award":["CNPq 573589\/08\u20139"],"award-info":[{"award-number":["CNPq 573589\/08\u20139"]}]},{"name":"Research Council of Lillebaelt Hospital, Denmark","award":["FAPESP 2008\/57887\u20139"],"award-info":[{"award-number":["FAPESP 2008\/57887\u20139"]}]},{"name":"Research Council of Lillebaelt Hospital, Denmark","award":["CNPq 573589\/08\u20139"],"award-info":[{"award-number":["CNPq 573589\/08\u20139"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A hereditary component of breast (BC) and colorectal cancer (CRC) has been described in approximately one-third of these tumor types. BC patients have an increased risk of developing CRC as a second primary tumor and vice versa. Germline genomic variants (NextSeq550, Illumina) were investigated in 24 unrelated BC and\/or CRC patients and 7 relatives from 3 index patients. Fifty-six pathogenic or likely pathogenic variants were identified in 19 of 24 patients. We detected single-nucleotide variants (SNVs) in CRC predisposition genes (MLH1 and MUTYH) and other promising candidates (CDK5RAP3, MAD1L1, NOS3, and POLM). Eighteen patients presented SNVs or copy number variants (CNVs) in DNA damage repair genes. We also identified SNVs recently associated with BC or CRC predisposition (PABPC1, TYRO3, MAP3K1, SLC15A4, and LAMA1). The PABPC1c.1255C&gt;T variant was detected in nine unrelated patients. Each patient presented at least one SNV\/CNV in a candidate gene, and most had alterations in more than one gene, reinforcing a polygenic model for BC\/CRC predisposition. A significant fraction of BC\/CRC patients with a family history of these tumors harbored deleterious germline variants in DNA repair genes. Our findings can lead to strategies to improve the diagnosis, genetic counseling, and treatment of patients and their relatives.<\/jats:p>","DOI":"10.3390\/ijms251910275","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T10:41:47Z","timestamp":1727174507000},"page":"10275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Germline DNA Damage Repair Gene Alterations in Patients with Metachronous Breast and Colorectal Cancer"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3851-2696","authenticated-orcid":false,"given":"Rolando Andr\u00e9 Rios","family":"Villacis","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark"},{"name":"Department of Genetics and Morphology, Institute of Biological Sciences, University of Bras\u00edlia-UnB, Bras\u00edlia 70910-900, DF, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza","family":"C\u00f4rtes","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark"},{"name":"Tocogynecology Graduation Program, Medical School, S\u00e3o Paulo State University UNESP, Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiane Ramos","family":"Basso","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9095-9431","authenticated-orcid":false,"given":"Luisa Matos","family":"do Canto","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4129-8769","authenticated-orcid":false,"given":"Jeferson Santos","family":"Souza","sequence":"additional","affiliation":[{"name":"Health Technology Institute, SENAI CIMATEC, Salvador 41650-010, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4742-7047","authenticated-orcid":false,"given":"Mads Malik","family":"Aagaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1187-1384","authenticated-orcid":false,"given":"Maria Nirvana","family":"da Cruz Formiga","sequence":"additional","affiliation":[{"name":"Department of Oncogenetics and Clinical Oncology, A.C. Camargo Cancer Center, S\u00e3o Paulo 01509-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Samuel","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Reference Center, A.C. Camargo Cancer Center, S\u00e3o Paulo 01509-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Isabel","family":"Achatz","sequence":"additional","affiliation":[{"name":"Cancer Genetics Unit, Oncology Branch, Hospital Sirio-Liban\u00eas, S\u00e3o Paulo 01308-050, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4637-5687","authenticated-orcid":false,"given":"Silvia Regina","family":"Rogatto","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark"},{"name":"Institute of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark"},{"name":"Danish Colorectal Cancer Center South, 7100 Vejle, Denmark"},{"name":"Botucatu Medical School Hospital, S\u00e3o Paulo State University UNESP, Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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