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
- Publication date
- Publisher
- Biomed Central
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