{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:32:00Z","timestamp":1768314720853,"version":"3.49.0"},"reference-count":138,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/BIM\/00009\/2019"],"award-info":[{"award-number":["UID\/BIM\/00009\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The incidence of thyroid cancer (TC), particularly well-differentiated forms (DTC), has been rising and remains the highest among endocrine malignancies. Although ionizing radiation (IR) is well established on DTC aetiology, other environmental and genetic factors may also be involved. DNA repair single nucleotide polymorphisms (SNPs) could be among the former, helping in explaining the high incidence. To further clarify the role of DNA repair SNPs in DTC susceptibility, we analyzed 36 SNPs in 27 DNA repair genes in a population of 106 DTCs and corresponding controls with the aim of interpreting joint data from previously studied isolated SNPs in DNA repair genes. Significant associations with DTC susceptibility were observed for XRCC3 rs861539, XPC rs2228001, CCNH rs2230641, MSH6 rs1042821 and ERCC5 rs2227869 and for a haplotype block on chromosome 5q. From 595 SNP-SNP combinations tested and 114 showing relevance, 15 significant SNP combinations (p &lt; 0.01) were detected on paired SNP analysis, most of which involving CCNH rs2230641 and mismatch repair variants. Overall, a gene-dosage effect between the number of risk genotypes and DTC predisposition was observed. In spite of the volume of data presented, new studies are sought to provide an interpretability of the role of SNPs in DNA repair genes and their combinations in DTC susceptibility.<\/jats:p>","DOI":"10.3390\/genes10080586","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T11:39:37Z","timestamp":1564659577000},"page":"586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes"],"prefix":"10.3390","volume":"10","author":[{"given":"Lu\u00eds S.","family":"Santos","sequence":"first","affiliation":[{"name":"Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School|Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Universidade Cat\u00f3lica Portuguesa, Center for Interdisciplinary Research in Health (CIIS), Institute of Health Sciences (ICS), 3504-505 Viseu, Portugal"}]},{"given":"Bruno Costa","family":"Gomes","sequence":"additional","affiliation":[{"name":"Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School|Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]},{"given":"H\u00e9lder N.","family":"Bastos","sequence":"additional","affiliation":[{"name":"Department of Pneumology, Centro Hospitalar S\u00e3o Jo\u00e3o, 4200\u2013319 Porto, Portugal"},{"name":"Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"IBMC\/i3S - Instituto de Biologia Molecular e Celular\/Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Oct\u00e1via M.","family":"Gil","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 2695-066 Bobadela LRS, Loures, Portugal"}]},{"given":"Ana Paula","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School|Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Department of Clinical Pathology, Hospital S\u00e3o Francisco Xavier, 1449-005 Lisboa, Portugal"}]},{"given":"Teresa C.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Medicina Nuclear, Instituto Portugu\u00eas de Oncologia de Lisboa (IPOLFG), 1099-023 Lisboa, Portugal"}]},{"given":"Edward","family":"Limbert","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Endocrinologia, Instituto Portugu\u00eas de Oncologia de Lisboa (IPOLFG), 1099-023 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9122-0732","authenticated-orcid":false,"given":"Susana N.","family":"Silva","sequence":"additional","affiliation":[{"name":"Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School|Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]},{"given":"Jos\u00e9","family":"Rueff","sequence":"additional","affiliation":[{"name":"Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School|Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,1]]},"reference":[{"key":"ref_1","unstructured":"Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. 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