title: Polymorphisms within base and nucleotide excision repair pathways and risk of differentiated thyroid carcinoma.
abstract: The thyrocytes are exposed to high levels of oxidative stress which could induce DNA damages. Base excision repair (BER) is one of the principal mechanisms of defense against oxidative DNA damage, however recent evidences suggest that also nucleotide excision repair (NER) could be involved. The aim of present work was to identify novel differentiated thyroid cancer (DTC) risk variants in BER and NER genes. For this purpose, the most strongly associated SNPs within NER and BER genes found in our previous GWAS on DTC were selected and replicated in an independent series of samples for a new case-control study. Although a positive signal was detected at the nominal level of 0.05 for rs7689099 (encoding for an aminoacid change proline to arginine at codon 117 within NEIL3), none of the considered SNPs (i.e. rs7990340 and rs690860 within RFC3, rs3744767 and rs1131636 within RPA1, rs16962916 and rs3136166 in ERCC4, and rs17739370 and rs7689099 in NEIL3) was associated with the risk of DTC when the correction of multiple testing was applied. In conclusion, a role of NER and BER pathways was evoked in the susceptibility to DTC. However, this seemed to be limited to few polymorphic genes and the overall effect size appeared weak.
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cipollini
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Gisella
authors.initials: G
authors.lastname: Figlioli
authors.affiliation: Center for Nanotechnology and Innovation @NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maccari
authors.affiliation: Center for Integrated Biology, University of Trento, Trento, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Garritano
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: De Santi
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Ombretta
authors.initials: O
authors.lastname: Melaiu
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Barone
authors.affiliation: Blood Centre of University Hospital of Meyer, Florence, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Bambi
authors.affiliation: Blood Centre of University Hospital of Meyer, Florence, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ermini
authors.affiliation: Operative Unit of laboratory of Clinical Chemistry Analyses, University Hospital of Cisanello, Pisa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellegrini
authors.affiliation: Department of Endocrinology and Metabolism, Orthopaedics and Traumatology, Occupational Medicine, University of Pisa, Pisa, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cristaudo
authors.affiliation: Department of Endocrinology and Metabolism, Orthopaedics and Traumatology, Occupational Medicine, University of Pisa, Pisa, Italy.
authors.forename: Rudy
authors.initials: R
authors.lastname: Foddis
authors.affiliation: Department of Endocrinology and Metabolism, Orthopaedics and Traumatology, Occupational Medicine, University of Pisa, Pisa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bonotti
authors.affiliation: Department of Endocrinology and Metabolism, Orthopaedics and Traumatology, Occupational Medicine, University of Pisa, Pisa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Romei
authors.affiliation: Operative Unit of laboratory of Clinical Chemistry Analyses, University Hospital of Cisanello, Pisa, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Vivaldi
authors.affiliation: Department of Endocrinology and Metabolism, Orthopaedics and Traumatology, Occupational Medicine, University of Pisa, Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Agate
authors.affiliation: Department of Endocrinology and Metabolism, Orthopaedics and Traumatology, Occupational Medicine, University of Pisa, Pisa, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Molinari
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Barale
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.
authors.forename: Asta
authors.initials: A
authors.lastname: Forsti
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.affiliation: Department of Endocrinology and Metabolism, Orthopaedics and Traumatology, Occupational Medicine, University of Pisa, Pisa, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Elisei
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Gemignani
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy. Electronic address: stefano.landi@unipi.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Landi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
keywords: BER; Differentiated thyroid cancer risk; NER; Polymorphism