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This Article Accepted manuscript (PDF) All Versions of this Article: ERC-08-0336v1 16/2/491    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Akulevich, N. Articles by Yamashita, S. Search for Related Content PubMed PubMed Citation Articles by Akulevich, N. Articles by Yamashita, S.

N Akulevich, Molecular Medicine, Nagasaki University, Nagasaki, Japan
V Saenko, International Health and Radiation Research, Nagasaki University, Nagasaki, 852-8523, Japan
T Rogounovitch, Molecular Medicine, Nagasaki University, Nagasaki, Japan
V Drozd, Thyroid Disease Research, Belarusian Medical Academy for Postgraduate Education, Minsk, Belarus
E Lushnikov, Pathology, Medical Radiological Research Center RAMS, Obninsk, Russian Federation
V Ivanov, National Radiation Epidemiology Registry, Medical Radiological Research Center RAMS, Obninsk, Russian Federation
N Mitsutake, Molecular Medicine, Nagasaki University, Nagasaki, Japan
R Kominami, Molecular Genetics, Niigata University, Niigata, Japan
S Yamashita, Molecular Medicine, Nagasaki University, Nagasaki, Japan

Correspondence: Vladimir Saenko, Email: saenko{at}net.nagasaki-u.ac.jp

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 (OR=0.69, 95% 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 IR-induced or sporadic PTCs.