Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes
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 si...
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| Veröffentlicht in: | Genes 2019-08, Vol.10 (8), p.586 |
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| creator | Santos, Luís S Gomes, Bruno Costa Bastos, Hélder N Gil, Octávia M Azevedo, Ana Paula Ferreira, Teresa C Limbert, Edward Silva, Susana N Rueff, José |
| description | 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
rs861539,
rs2228001,
rs2230641,
rs1042821 and
rs2227869 and for a haplotype block on chromosome 5q. From 595 SNP-SNP combinations tested and 114 showing relevance, 15 significant SNP combinations (
< 0.01) were detected on paired SNP analysis, most of which involving
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. |
| doi_str_mv | 10.3390/genes10080586 |
| format | Article |
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rs861539,
rs2228001,
rs2230641,
rs1042821 and
rs2227869 and for a haplotype block on chromosome 5q. From 595 SNP-SNP combinations tested and 114 showing relevance, 15 significant SNP combinations (
< 0.01) were detected on paired SNP analysis, most of which involving
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.</description><identifier>ISSN: 2073-4425</identifier><identifier>EISSN: 2073-4425</identifier><identifier>DOI: 10.3390/genes10080586</identifier><identifier>PMID: 31374908</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adult ; Age ; Aged ; base pair mismatch ; Cell cycle ; Chromosome 5 ; chromosomes ; Chromosomes, Human, Pair 5 - genetics ; Cyclin H - genetics ; Deoxyribonucleic acid ; DNA ; DNA Repair ; DNA-Binding Proteins - genetics ; Dosage ; Endonucleases - genetics ; etiology ; Family medical history ; Female ; Gender ; Gene dosage ; Genes ; Genetic factors ; Genetic Predisposition to Disease ; Genotype & phenotype ; Haplotypes ; Humans ; Ionizing radiation ; Male ; Medical prognosis ; Middle Aged ; Mismatch repair ; MSH6 protein ; Nuclear Proteins - genetics ; Polymerase chain reaction ; Polymorphism ; Polymorphism, Single Nucleotide ; Radiation ; risk ; Single-nucleotide polymorphism ; Susceptibility ; Thyroid cancer ; thyroid neoplasms ; Thyroid Neoplasms - genetics ; Transcription Factors - genetics ; XPC protein</subject><ispartof>Genes, 2019-08, Vol.10 (8), p.586</ispartof><rights>2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-6974d8a4747004f509a1e29778439cf894e4088a878d84482d4280a892a6d3723</citedby><cites>FETCH-LOGICAL-c475t-6974d8a4747004f509a1e29778439cf894e4088a878d84482d4280a892a6d3723</cites><orcidid>0000-0002-9122-0732</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722859/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722859/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31374908$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Santos, Luís S</creatorcontrib><creatorcontrib>Gomes, Bruno Costa</creatorcontrib><creatorcontrib>Bastos, Hélder N</creatorcontrib><creatorcontrib>Gil, Octávia M</creatorcontrib><creatorcontrib>Azevedo, Ana Paula</creatorcontrib><creatorcontrib>Ferreira, Teresa C</creatorcontrib><creatorcontrib>Limbert, Edward</creatorcontrib><creatorcontrib>Silva, Susana N</creatorcontrib><creatorcontrib>Rueff, José</creatorcontrib><title>Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes</title><title>Genes</title><addtitle>Genes (Basel)</addtitle><description>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
rs861539,
rs2228001,
rs2230641,
rs1042821 and
rs2227869 and for a haplotype block on chromosome 5q. From 595 SNP-SNP combinations tested and 114 showing relevance, 15 significant SNP combinations (
< 0.01) were detected on paired SNP analysis, most of which involving
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.</description><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>base pair mismatch</subject><subject>Cell cycle</subject><subject>Chromosome 5</subject><subject>chromosomes</subject><subject>Chromosomes, Human, Pair 5 - genetics</subject><subject>Cyclin H - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Repair</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Dosage</subject><subject>Endonucleases - genetics</subject><subject>etiology</subject><subject>Family medical history</subject><subject>Female</subject><subject>Gender</subject><subject>Gene dosage</subject><subject>Genes</subject><subject>Genetic factors</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype & phenotype</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Ionizing radiation</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Mismatch repair</subject><subject>MSH6 protein</subject><subject>Nuclear Proteins - genetics</subject><subject>Polymerase chain reaction</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Radiation</subject><subject>risk</subject><subject>Single-nucleotide polymorphism</subject><subject>Susceptibility</subject><subject>Thyroid cancer</subject><subject>thyroid neoplasms</subject><subject>Thyroid Neoplasms - genetics</subject><subject>Transcription Factors - genetics</subject><subject>XPC protein</subject><issn>2073-4425</issn><issn>2073-4425</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkcFLwzAYxYMoKnNHrxLw4qWaJl-bxIMgU6cgijrPIWvTLdI1M2kH--_NmI7pxVy-QH687708hI5Tcs6YJBcT05iQEiJIJvIddEgJZwkAzXa37geoH8IHiQcIJSTbRwcsZRwkEYfoeTRdemdLPNBNYfwlHk0NfulMaHHlPB7GBa0t8FsXCjNv7djWtl3ih2bh6oVtJvjm6Rq_mrm2azYcob1K18H0v2cPvd_djgb3yePz8GFw_ZgUwLM2ySWHUmjgwKOtKiNSp4ZKzgUwWVRCggEihBZclAJA0BKoIFpIqvOSccp66GqtO-_GM1MWpmm9rtXc25n2S-W0Vb9fGjtVE7dQOadUZDIKnH0LePe5yqtmNmasa90Y1wVFAUgumczF_yiNUJrS6L2HTv-gH67zTfwJRTNYJckhjVSypgrvQvCm2vhOiVoVq34VG_mT7bAb-qdG9gWF9pwh</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Santos, Luís S</creator><creator>Gomes, Bruno Costa</creator><creator>Bastos, Hélder N</creator><creator>Gil, Octávia M</creator><creator>Azevedo, Ana Paula</creator><creator>Ferreira, Teresa C</creator><creator>Limbert, Edward</creator><creator>Silva, Susana N</creator><creator>Rueff, José</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9122-0732</orcidid></search><sort><creationdate>20190801</creationdate><title>Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes</title><author>Santos, Luís S ; 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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
rs861539,
rs2228001,
rs2230641,
rs1042821 and
rs2227869 and for a haplotype block on chromosome 5q. From 595 SNP-SNP combinations tested and 114 showing relevance, 15 significant SNP combinations (
< 0.01) were detected on paired SNP analysis, most of which involving
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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31374908</pmid><doi>10.3390/genes10080586</doi><orcidid>https://orcid.org/0000-0002-9122-0732</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Age Aged base pair mismatch Cell cycle Chromosome 5 chromosomes Chromosomes, Human, Pair 5 - genetics Cyclin H - genetics Deoxyribonucleic acid DNA DNA Repair DNA-Binding Proteins - genetics Dosage Endonucleases - genetics etiology Family medical history Female Gender Gene dosage Genes Genetic factors Genetic Predisposition to Disease Genotype & phenotype Haplotypes Humans Ionizing radiation Male Medical prognosis Middle Aged Mismatch repair MSH6 protein Nuclear Proteins - genetics Polymerase chain reaction Polymorphism Polymorphism, Single Nucleotide Radiation risk Single-nucleotide polymorphism Susceptibility Thyroid cancer thyroid neoplasms Thyroid Neoplasms - genetics Transcription Factors - genetics XPC protein |
| title | Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes |
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