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 singlenucleotide 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)Z0.69, 95% confidence interval (CI) 0.45-0.86 and ORZ0.70, 95% CI 0.59-0.93 respectively). The ATM IVS22-77 TOC and TP53 Arg72Pro SNPs interacted with radiation (PZ0.04 and PZ0.01 respectively). ATM IVS22-77 associated with the increased risk of sporadic PTC (ORZ1.84, 95% CI 1.10-3.24) whereas TP53 Arg72Pro correlated with the higher risk of radiogenic PTC (ORZ1.80, 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 (ORZ2.10, 95% CI 1.17-3.78). The GG/CC/GG/GG genotype displayed a significantly increased risk for sporadic PTC (ORZ3.32, 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.

X-Ray Repair Cross-Complementing Group 1(XRCC1) Genetic Polymorphisms and Thyroid Carcinoma Risk: a Meta-Analysis

“…However, the results were not consistent. For example, Ryu's study (Ryu et al, 2011) have found that the XRCC1 Arg194Trp Arg/ Trp genotype was significantly associated with a decreased risk of papillary thyroid carcinoma compared to that of Arg/Arg genotype (OR with 95 CI;), however, no such association was observed in Esfahani's study (Fard-Esfahani et al, 2011); Quispes's study (García-Quispes et al, 2011) have found a positive association (OR = 1.58, 95% CI 1.05-2.46) for XRCC1 Arg280His, however, no such tendency was found in Chiang's study (Chiang et al, 2008); Akulevich's study (Akulevich et al, 2009) have found that XRCC1 Arg399Gln polymorphisms was associated with a decreased risk of PTC according to the multiplicative and dominant models of inheritance, however, Siraj's study (Siraj et al, 2008) found no such association. These inconsistent results failed to clarify the complicated relationship between XRCC1 polymorphism and thyroid cancer risk.…”

“…There are also some case-control studies conducted to explore the association of SNPs of XRCC1 and thyroid cancer risk (Zhu et al, 2004;Chiang et al, 2008;Siraj et al, 2008;Akulevich et al, 2009;Ho et al, 2009;Sigurdson et al, 2009;Fard-Esfahani et al, 2011;García-Quispes et al, 2011;Ryu et al, 2011). However, the results were not consistent.…”

Associations Between XRCC1 Arg399Gln, Arg194Trp, and Arg280His Polymorphisms and Risk of Differentiated Thyroid Carcinoma: A Meta-analysis

“…Figure 1 illustrates the study selection process and the detailed characteristics of the included studies are shown in Table 1. A total of 10 published studies (1,606 DTC patients and 3,577 controls) were included in the Arg399Gln analysis (Zhu et al, 2004;Siraj et al, 2008;Chiang et al, 2008;Ho et al, 2009;Akulevich et al, 2009;Sigurdson et al, 2009;Ryu et al, 2011;Garcia-Quispes et al, 2011;Fard-Esfahani et al, 2011;Santos et al, 2012) Santos et al, 2012). The genotypic distribution of the controls was consistent with HWE, with the exception of two studies (Sigurdson et al, 2009;Ryu et al, 2011).…”

Risk factors for subsequent endocrine-related cancer in childhood cancer survivors

“…Best and coworkers identified allelic variants in PRDM1 to predispose Hodgkin lymphoma survivors to radiation-induced thyroid cancer (Best et al 2011). In addition, several studies identified allelic variants in TP53, ATM and FOXE1 to be associated with radiationinduced papillary thyroid carcinoma in survivors of the Chernobyl nuclear accident (Akulevich et al 2009, Takahashi et al 2010, Damiola et al 2014). …”