Polymorphic ATM gene variants in radiation-induced and sporadic papillary thyroid cancer in children

抄録

Background: the ATM gene plays a key role in ionizing radiation (IR)-induced DNA damage sensing. Purpose of the study was to assess possible correlation between ATM single nucleotide polymorphisms (SNPs) and papillary thyroid cancer (PTC) of different etiology in children. Methods: rs1801516 G>A (exon 39), rs664677 T>C (intron 22) and rs609429 C>G (intron 48) ATM SNPs were profiled in 85 Caucasian patients with pediatric IR-induced (n=40) and sporadic (n=49) PTCs by PCR/RFLP and direct sequencing. Statistical analysis was done using Fisher’s exact test. Results: The shift towards the rare allele-carrying rs1801516 genotypes was found in pediatric IR-induced PTCs compared to sporadic ones (47.5% vs. 24.5%; P=0.03; OR=2.8; 95% CI 1.1-6.9). Unexpectedly, the analysis of rs1801516/rs664677/rs609429 SNP combinations revealed no individuals with homozygous wild-type GG/TT/CC genotype among IR-induced cases. In the sporadic PTC group, the frequency of this genotype was 14.6%. The most common genotype detected in both groups was GG/TC/CG (29.7% vs. 43.8% in IR-induced and sporadic PTCs, respectively; P=0.3; OR=0.5; 95% CI 0.2-1.3). The GA/TC/CG combination showed a tendency to dominate in the IR-induced group compared to sporadic PTC (16.2% vs. 4.2%; P=0.07; OR=4.4; 95% CI 0.8-23.0). Conclusion: ATM rs1801516 harboring the rare allele (mostly the GA) and the GA/TC/CG genotype may contribute to the risk of IR-induced PTC in childhood; however this observation needs to be confirmed using a larger sample size