Thyroid cancer: the quest for genetic susceptibility involving DNA repair genes

Luís S. Santos; Bruno Costa Gomes; Hélder N. Bastos; Octávia M. Gil; Ana Paula Azevedo; Teresa C. Ferreira; Edward Limbert; Susana N. Silva; José Rueff

doi:10.3390/genes10080586

Thyroid cancer: the quest for genetic susceptibility involving DNA repair genes

Luís S. Santos, Bruno Costa Gomes, Hélder N. Bastos, Octávia M. Gil, Ana Paula Azevedo, Teresa C. Ferreira, Edward Limbert, Susana N. Silva^*, José Rueff

^*Corresponding author for this work

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Abstract

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 < 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.

Original language	English
Article number	586
Journal	Genes
Volume	10
Issue number	8
DOIs	https://doi.org/10.3390/genes10080586
Publication status	Published - Aug 2019

Keywords

DNA repair
Genetic markers
Genetic susceptibility
SNPs
Thyroid cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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20156360Final published version, 800 KBLicence: CC BY

http://hdl.handle.net/10400.14/32609Licence: CC BY

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@article{b1dd42fa2dec4de39327bff898f1616f,

title = "Thyroid cancer: the quest for genetic susceptibility involving DNA repair genes",

abstract = "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 < 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.",

keywords = "DNA repair, Genetic markers, Genetic susceptibility, SNPs, Thyroid cancer",

author = "Santos, {Lu{\'i}s S.} and Gomes, {Bruno Costa} and Bastos, {H{\'e}lder N.} and Gil, {Oct{\'a}via M.} and Azevedo, {Ana Paula} and Ferreira, {Teresa C.} and Edward Limbert and Silva, {Susana N.} and Jos{\'e} Rueff",

note = "Funding Information: Funding: This work was supported by FCT – Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (Portuguese Foundation for Science and Technology) through Project UID/BIM/00009/2019-Centre for Toxicogenomics and Human Health. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

month = aug,

doi = "10.3390/genes10080586",

language = "English",

volume = "10",

journal = "Genes",

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T2 - the quest for genetic susceptibility involving DNA repair genes

AU - Santos, Luís S.

AU - Gomes, Bruno Costa

AU - Bastos, Hélder N.

AU - Gil, Octávia M.

AU - Azevedo, Ana Paula

AU - Ferreira, Teresa C.

AU - Limbert, Edward

AU - Silva, Susana N.

AU - Rueff, José

N1 - Funding Information: Funding: This work was supported by FCT – Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) through Project UID/BIM/00009/2019-Centre for Toxicogenomics and Human Health. Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/8

Y1 - 2019/8

N2 - 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 < 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.

AB - 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 < 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.

KW - DNA repair

KW - Genetic markers

KW - Genetic susceptibility

KW - SNPs

KW - Thyroid cancer

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DO - 10.3390/genes10080586

M3 - Article

C2 - 31374908

AN - SCOPUS:85071027633

SN - 2073-4425

VL - 10

JO - Genes

JF - Genes

IS - 8

M1 - 586

ER -

Thyroid cancer: the quest for genetic susceptibility involving DNA repair genes

Abstract

Keywords

UN SDGs

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