Investigation of DNA repair-related SNPs underlying susceptibility to papillary thyroid carcinoma reveals MGMT as a novel candidate gene in Belarusian children exposed to radiation.
BMC Cancer
; 17(1): 328, 2017 05 12.
Article
em En
| MEDLINE
| ID: mdl-28499365
ABSTRACT
BACKGROUND:
Genetic factors may influence an individual's sensitivity to ionising radiation and therefore modify his/her risk of developing papillary thyroid carcinoma (PTC). Previously, we reported that common single nucleotide polymorphisms (SNPs) within the DNA damage recognition gene ATM contribute to PTC risk in Belarusian children exposed to fallout from the Chernobyl power plant accident. Here we explored in the same population the contribution of a panel of DNA repair-related SNPs in genes acting downstream of ATM.METHODS:
The association of 141 SNPs located in 43 DNA repair genes was examined in 75 PTC cases and 254 controls from the Gomel region in Belarus. All subjects were younger than 15 years at the time of the Chernobyl accident. Conditional logistic regressions accounting for radiation dose were performed with PLINK using the additive allelic inheritance model, and a linkage disequilibrium (LD)-based Bonferroni correction was used for correction for multiple testing.RESULTS:
The intronic SNP rs2296675 in MGMT was associated with an increased PTC risk [per minor allele odds ratio (OR) 2.54 95% CI 1.50, 4.30, P per allele = 0.0006, P corr.= 0.05], and gene-wide association testing highlighted a possible role for ERCC5 (P Gene = 0.01) and PCNA (P Gene = 0.05) in addition to MGMT (P Gene = 0.008).CONCLUSIONS:
These findings indicate that several genes acting in distinct DNA repair mechanisms contribute to PTC risk. Further investigation is needed to decipher the functional properties of the methyltransferase encoded by MGMT and to understand how alteration of such functions may lead to the development of the most common type of thyroid cancer.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Glândula Tireoide
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Carcinoma Papilar
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Metilases de Modificação do DNA
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Polimorfismo de Nucleotídeo Único
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Proteínas Supressoras de Tumor
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Enzimas Reparadoras do DNA
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Acidente Nuclear de Chernobyl
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Reparo do DNA
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Neoplasias Induzidas por Radiação
Tipo de estudo:
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Female
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Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
BMC Cancer
Ano de publicação:
2017
Tipo de documento:
Article