Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma

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.

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Punicalagin from pomegranate promotes human papillary thyroid carcinoma BCPAP cell death by triggering ATM-mediated DNA damage response

Nutrition Research ◽

10.1016/j.nutres.2017.09.001 ◽

2017 ◽

Vol 47 ◽

pp. 63-71 ◽

Cited By ~ 9

Author(s):

Xin Yao ◽

Xian Cheng ◽

Li Zhang ◽

Huixin Yu ◽

Jiandong Bao ◽

...

Keyword(s):

Dna Damage ◽

Cell Death ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Dna Damage Response ◽

Papillary Thyroid ◽

Damage Response

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An Enriched Environment Alters DNA Repair and Inflammatory Responses After Radiation Exposure

Frontiers in Immunology ◽

10.3389/fimmu.2021.760322 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sae Sakama ◽

Keisuke Kurusu ◽

Mayu Morita ◽

Takashi Oizumi ◽

Shinya Masugata ◽

...

Keyword(s):

Dna Damage ◽

Inflammatory Response ◽

Radiation Exposure ◽

Dna Damage Response ◽

Inflammatory Responses ◽

Enriched Environment ◽

Physical And Mental Health ◽

Chronic Inflammatory Response ◽

Damage Response ◽

Radiation Induced

After the Fukushima Daiichi Nuclear Power Plant accident, there is growing concern about radiation-induced carcinogenesis. In addition, living in a long-term shelter or temporary housing due to disasters might cause unpleasant stress, which adversely affects physical and mental health. It’s been experimentally demonstrated that “eustress”, which is rich and comfortable, has beneficial effects for health using mouse models. In a previous study, mice raised in the enriched environment (EE) has shown effects such as suppression of tumor growth and enhancement of drug sensitivity during cancer treatment. However, it’s not yet been evaluated whether EE affects radiation-induced carcinogenesis. Therefore, to evaluate whether EE suppresses a radiation-induced carcinogenesis after radiation exposure, in this study, we assessed the serum leptin levels, radiation-induced DNA damage response and inflammatory response using the mouse model. In brief, serum and tissues were collected and analyzed over time in irradiated mice after manipulating the raising environment during the juvenile or adult stage. To assess the radiation-induced DNA damage response, we performed immunostaining for phosphorylated H2AX which is a marker of DNA double-strand break. Focusing on the polarization of macrophages in the inflammatory reaction that has an important role in carcinogenesis, we performed analysis using tissue immunofluorescence staining and RT-qPCR. Our data confirmed that EE breeding before radiation exposure improved the responsiveness to radiation-induced DNA damage and basal immunity, further suppressing the chronic inflammatory response, and that might lead to a reduction of the risk of radiation-induced carcinogenesis.

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Association between hTERT Polymorphisms and Female Papillary Thyroid Carcinoma

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892814666190919145453 ◽

2019 ◽

Vol 14 (3) ◽

pp. 268-279

Author(s):

Ying Liu ◽

Zhi Li ◽

Xinyue Tang ◽

Min Li ◽

Feng Shi

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Genome Wide Association Study ◽

Papillary Thyroid ◽

Clinicopathologic Characteristics ◽

Female Population ◽

Genome Wide ◽

Increased Risk ◽

Significant Difference ◽

Thyroid Cancer Risk

Background: A previous genome-wide association study showed that hTERT rs10069690 and rs2736100 polymorphisms were associated with thyroid cancer risk. Objective: This study further investigated the association between increased risk and clinicopathologic characteristics for Papillary Thyroid Carcinoma (PTC) and hTERT polymorphisms rs10069690 or rs2736100 in a Chinese female population. Methods: The hTERT genotypes of 276 PTC patients and 345 healthy subjects were determined with regard to SNPs rs10069690 and rs2736100. The association between these SNPs and the risk of PTC and clinicopathologic characteristics was investigated by logistic regression. Results: We found a significant difference between PTC and rs10069690 (Odds Ratio (OR) = 1.515; P = 0.005), but not between PTC and rs2736100. When the analysis was limited to females, rs10069690 and rs2736100 were both associated with increased risk for PTC in female individuals (OR = 1.647, P = 0.007; OR = 1.339, P = 0.041, respectively). Further haplotype analysis revealed a stimulative effect of haplotypes TC and CA of TERT rs10069690-rs2736100, which increased risk for PTC in female individuals (OR = 1.579, P = 0.014; OR = 0.726, P = 0.025, respectively). Furthermore, the heterozygote A/C of rs2736100 showed significant difference for age (OR = 0.514, P = 0.047). Conclusion: Our finding suggests that hTERT polymorphisms rs10069690 and rs2736100 are associated with increased risk for PTC in Chinese female population and rs2736100 may be related to age. Consistent with US20170360914 and US20170232075, they are expected to be a potential molecular target for anti-cancer therapy.

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Genetic Determinants for Prediction of Outcome of Patients with Papillary Thyroid Carcinoma

Cancers ◽

10.3390/cancers13092048 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2048

Author(s):

Antónia Afonso Póvoa ◽

Elisabete Teixeira ◽

Maria Rosa Bella-Cueto ◽

Rui Batista ◽

Ana Pestana ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Patient Outcomes ◽

Genetic Alterations ◽

Papillary Thyroid ◽

Tissue Samples ◽

Primary Tumors ◽

Persistent Disease ◽

Increased Risk ◽

Structural Disease

Papillary thyroid carcinoma (PTC) usually presents an excellent prognosis, but some patients present with aggressive metastatic disease. BRAF, RAS, and TERT promoter (TERTp) genes are altered in PTC, and their impact on patient outcomes remains controversial. We aimed to determine the role of genetic alterations in PTC patient outcomes (recurrent/persistent disease, structural disease, and disease-specific mortality (DSM)). The series included 241 PTC patients submitted to surgery, between 2002–2015, in a single hospital. DNA was extracted from tissue samples of 287 lesions (primary tumors and metastases). Molecular alterations were detected by Sanger sequencing. Primary tumors presented 143 BRAF, 16 TERTp, and 13 RAS mutations. Isolated TERTpmut showed increased risk of structural disease (HR = 7.0, p < 0.001) and DSM (HR = 10.1, p = 0.001). Combined genotypes, BRAFwt/TERTpmut (HR = 6.8, p = 0.003), BRAFmut/TERTpmut (HR = 3.2, p = 0.056) and BRAFmut/TERTpwt (HR = 2.2, p = 0.023) showed increased risk of recurrent/persistent disease. Patients with tumors BRAFwt/TERTpmut (HR = 24.2, p < 0.001) and BRAFmut/TERTpmut (HR = 11.5, p = 0.002) showed increased risk of structural disease. DSM was significantly increased in patients with TERTpmut regardless of BRAF status (BRAFmut/TERTpmut, log-rank p < 0.001; BRAFwt/TERTpmut, log-rank p < 0.001). Our results indicate that molecular markers may have a role in predicting PTC patients’ outcome. BRAFmut/TERTpwt tumors were prone to associate with local aggressiveness (recurrent/persistent disease), whereas TERTpmut tumors were predisposed to recurrent structural disease and DSM.

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