Among 45 variants in 11 genes, HDM2 promoter polymorphisms emerge as new candidate biomarker associated with radiation toxicity

El-Sebaie, Medhat; Al-Rajhi, Nasser; Al-Harbi, Najla; Al-Hadyan, Khaled; Al-Qahtani, Sara; Alsubael, Mohammad; Al-Shabanah, Mohammad; Moftah, Belal

doi:10.1007/s13205-013-0135-3

Cited by 12 publications

(8 citation statements)

References 56 publications

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“…(2016) who found an association with the SNPs rs1695 and A313G. Only the SNP rs1801516 in ATM was found to be associated with adverse skin reactions by Alsbeih et al. (2014), Zhang et al.…”

Section: Prospects For Predicting Individual Response To Ionising mentioning

confidence: 99%

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Human individual radiation sensitivity and prospects for prediction

et al. 2018

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In the past few decades, it has become increasingly evident that sensitivity to ionising radiation is variable. This is true for tissue reactions (deterministic effects) after high doses of radiation, for stochastic effects following moderate and possibly low doses, and conceivably also for non-cancer effects such as cardiovascular disease, the causal pathway(s) of which are not yet fully understood. A high sensitivity to deterministic effects is not necessarily correlated with a high sensitivity to stochastic effects. The concept of individual sensitivity to high and low doses of radiation has long been supported by data from patients with certain rare hereditary conditions. However, these syndromes only affect a small proportion of the general population. More relevant to the majority of the population is the notion that some part of the genetic contribution defining radiation sensitivity may follow a polygenic model, which predicts elevated risk resulting from the inheritance of many low-penetrance risk-modulating alleles. Can the different forms of individual radiation sensitivities be inferred from the reaction of cells exposed ex vivo to ionising radiation? Can they be inferred from analyses of individual genotypes? This paper reviews current evidence from studies of late adverse tissue reactions after radiotherapy in potentially sensitive groups, including data from functional assays, candidate gene approaches, and genome-wide association studies. It focuses on studies published in 2013 or later because a comprehensive review of earlier studies was published previously in a report by the UK Advisory Group on Ionising Radiation.

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“…(2016) who found an association with the SNPs rs1695 and A313G. Only the SNP rs1801516 in ATM was found to be associated with adverse skin reactions by Alsbeih et al. (2014), Zhang et al.…”

Section: Prospects For Predicting Individual Response To Ionising mentioning

confidence: 99%

“…Although there was some overlap in the SNPs across studies, with the exception of ATM , no common SNPs were identified: XRCC1 was analysed by Seibold et al. (2015) and Alsbeih et al. (2014), who found an association between late effects and the following SNPs: rs2682585, G28152A, and rs25487.…”

Section: Prospects For Predicting Individual Response To Ionising mentioning

confidence: 99%

Human individual radiation sensitivity and prospects for prediction

et al. 2018

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“…Studies evaluating the long-term effects of radiation in humans are confounded by factors that include socioeconomic status, genetic variation, postirradiation survival interval and comorbidities such as cancer, hypertension and diabetes mellitus (33)(34)(35). These factors can be controlled for in rodent studies, and radiation-induced changes in the brain have been extensively characterized in rodents, including impairments in neurogenesis (36)(37)(38), changes in dendritic spine morphology and density (39)(40)(41), changes in neuroinflammation and ATP production (18), impaired glutamatergic neurotransmission (42)(43)(44)(45)(46), and increased astrocytic and microglial inflammation (47)(48)(49)(50)(51)(52)(53)(54)(55).…”

Section: Introductionmentioning

confidence: 99%

Non-Human Primates Receiving High-Dose Total-Body Irradiation are at Risk of Developing Cerebrovascular Injury Years Postirradiation

Andrews

Bloomer

Olson³

et al. 2020

Radiation Research

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Nuclear accidents and acts of terrorism have the potential to expose thousands of people to high-dose total-body iradiation (TBI). Those who survive the acute radiation syndrome are at risk of developing chronic, degenerative radiation-induced injuries [delayed effects of acute radiation (DEARE)] that may negatively affect quality of life. A growing body of literature suggests that the brain may be vulnerable to radiation injury at survivable doses, yet the long-term consequences of high-dose TBI on the adult brain are unclear. Herein we report the occurrence of lesions consistent with cerebrovascular injury, detected by susceptibility-weighted magnetic resonance imaging (MRI), in a cohort of non-human primate [(NHP); rhesus macaque, Macaca mulatta] long-term survivors of high-dose TBI (1.1-8.5 Gy). Animals were monitored longitudinally with brain MRI (approximately once every three years). Susceptibilityweighted images (SWI) were reviewed for hypointensities (cerebral microbleeds and/or focal necrosis). SWI hypointensities were noted in 13% of irradiated NHP; lesions were not observed in control animals. A prior history of exposure was correlated with an increased risk of developing a lesion detectable by MRI (P ¼ 0.003). Twelve of 16 animals had at least one brain lesion present at the time of the first MRI evaluation; a subset of animals (n ¼ 7) developed new lesions during the surveillance period (3.7-11.3 years postirradiation). Lesions occurred with a predilection for white matter and the gray-white matter junction. The majority of animals with lesions had one to three SWI hypointensities, but some animals had multifocal disease (n ¼ 2). Histopathologic evaluation of deceased animals within the cohort (n ¼ 3) revealed malformation of the cerebral vasculature and remodeling of the blood vessel walls. There was no association between comorbid diabetes mellitus or hypertension with SWI lesion status. These data suggest that long-term TBI survivors may be at risk of developing cerebrovascular injury years after irradiation.

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“…Over the last decade, a number of candidate gene association studies has been conducted in cancer patients to assess the role of the ATM rs1801516 gene polymorphism as risk factor for normal tissue complications of radiotherapy, in particular in prostate cancer, however inconsistent results have been reported due to insufficient statistical power of most studies [33, 35–37]. Looking at another pathology with high incidence and health impact as breast cancer, we attempted to evaluate the association of rs1801516 with late skin side effects of radiotherapy for breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Impact of ATM rs1801516 on late skin reactions of radiotherapy for breast cancer: Evidences from a cohort study and a trial sequential meta-analysis

et al. 2019

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The relationship between the ataxia-telangiectasia mutated (ATM) rs1801516 gene polymorphism and risk of radiation-induced late skin side effects remains a highly debated issue. In the present study, we assessed the role of ATM rs1801516 as risk factor for radiation-induced fibrosis and telangiectasia, using the LENT-SOMA scoring scale in 285 breast cancer patients who received radiotherapy after breast conserving surgery. A systematic review with meta-analysis and trial sequential analysis (TSA) was then conducted to assess reliability of the accumulated evidence in breast cancer patients. In our cohort study, no association was found between ATM rs1801516 and grade ≥ 2 telangiectasia (GA+AA vs GG, HRadjusted: 0.699; 95%CI: 0.273–1.792, P = 0.459) or grade ≥ 2 fibrosis (GA+AA vs GG, HRadjusted: 1.175; 95%CI: 0.641–2.154, P = 0.604). Twelve independent cohorts of breast cancer patients were identified through the systematic review, of which 11 and 9 cohorts focused respectively on the association with radiation-induced fibrosis and radiation-induced telangiectasia. Pooled analyses of 10 (n = 2928 patients) and 12 (n = 2783) cohorts revealed, respectively, no association of ATM rs1801516 with radiation-induced telangiectasia (OR: 1.14; 95%CI: 0.88–1.48, P = 0.316) and a significant correlation with radiation-induced fibrosis (OR: 1.23; 95%CI: 1.00–1.51, P = 0.049), which however did not remain significant after TSA adjustment (TSA-adjusted 95%CI: 0.85–1.78). These results do not support an impact of ATM rs1801516 on late skin reactions of radiotherapy for breast cancer, nevertheless further large studies are still required for conclusive evidences.

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Among 45 variants in 11 genes, HDM2 promoter polymorphisms emerge as new candidate biomarker associated with radiation toxicity

Cited by 12 publications

References 56 publications

Human individual radiation sensitivity and prospects for prediction

Human individual radiation sensitivity and prospects for prediction

Non-Human Primates Receiving High-Dose Total-Body Irradiation are at Risk of Developing Cerebrovascular Injury Years Postirradiation

Impact of ATM rs1801516 on late skin reactions of radiotherapy for breast cancer: Evidences from a cohort study and a trial sequential meta-analysis

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