title: Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma.
abstract: Papillary thyroid carcinoma (PTC) etiologically occurs as a radiation-induced or sporadic malignancy. Genetic factors contributing to the susceptibility to either form remain unknown. In this retrospective case-control study, we evaluated possible associations between single-nucleotide polymorphisms (SNPs) in the candidate DNA damage response genes (ATM, XRCC1, TP53, XRCC3, MTF1) and risk of radiation-induced and sporadic PTC. A total of 255 PTC cases (123 Chernobyl radiation-induced and 132 sporadic, all in Caucasians) and 596 healthy controls (198 residents of Chernobyl areas and 398 subjects without history of radiation exposure, all Caucasians) were genotyped. The risk of PTC and SNPs interactions with radiation exposure were assessed by logistic regressions. The ATM G5557A and XRCC1 Arg399Gln polymorphisms, regardless of radiation exposure, associated with a decreased risk of PTC according to the multiplicative and dominant models of inheritance (odds ratio (OR) = 0.69, 95% confidence interval (CI) 0.45-0.86 and OR = 0.70, 95% CI 0.59-0.93 respectively). The ATM IVS22-77 T > C and TP53 Arg72Pro SNPs interacted with radiation (P = 0.04 and P = 0.01 respectively). ATM IVS22-77 associated with the increased risk of sporadic PTC (OR = 1.84, 95% CI 1.10-3.24) whereas TP53 Arg72Pro correlated with the higher risk of radiogenic PTC (OR = 1.80, 95% CI 1.06-2.36). In the analyses of ATM/TP53 (rs1801516/rs664677/rs609429/rs1042522) combinations, the GG/TC/CG/GC genotype strongly associated with radiation-induced PTC (OR = 2.10, 95% CI 1.17-3.78). The GG/CC/GG/GG genotype displayed a significantly increased risk for sporadic PTC (OR = 3.32, 95% CI 1.57-6.99). The results indicate that polymorphisms of DNA damage response genes may be potential risk modifiers of ionizing radiation-induced or sporadic PTCs.
authors.affiliation: Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
authors.forename: Natallia M
authors.initials: NM
authors.lastname: Akulevich
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Saenko
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Rogounovitch
authors.forename: Valentina M
authors.initials: VM
authors.lastname: Drozd
authors.forename: Eugeny F
authors.initials: EF
authors.lastname: Lushnikov
authors.forename: Victor K
authors.initials: VK
authors.lastname: Ivanov
authors.forename: Norisato
authors.initials: N
authors.lastname: Mitsutake
authors.forename: Ryo
authors.initials: R
authors.lastname: Kominami
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins; D002291:Carcinoma, Papillary / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011839:Radiation, Ionizing; D012189:Retrospective Studies; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1; D055815:Young Adult; D000097809:Transcription Factor MTF-1
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; D000097809:Transcription Factor MTF-1; C495901:TP53 protein, human; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C576324:ATM protein, human