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

Research output: Contribution to journalArticle

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 languageEnglish
Article number586
JournalGenes
Volume10
Issue number8
DOIs
Publication statusPublished - 1 Aug 2019

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Genetic Predisposition to Disease
Thyroid Neoplasms
Single Nucleotide Polymorphism
DNA Repair
Genes
DNA Mismatch Repair
Gene Dosage
Incidence
Ionizing Radiation
Haplotypes
Chromosomes
Joints
Genotype

Keywords

  • DNA repair
  • Genetic markers
  • Genetic susceptibility
  • SNPs
  • Thyroid cancer

Cite this

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. / Thyroid cancer : The quest for genetic susceptibility involving dna repair genes. In: Genes. 2019 ; Vol. 10, No. 8.
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Thyroid cancer : The quest for genetic susceptibility involving dna repair genes. / 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.

In: Genes, Vol. 10, No. 8, 586, 01.08.2019.

Research output: Contribution to journalArticle

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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

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