Variation in Telangiectasia Predisposing Genes Is Associated With Overall Radiation Toxicity

Tanteles, George A.; Murray, Robert; Mills, Jamie; Barwell, Julian; Chakraborti, Prabir; Chan, Steve; Cheung, Kwok-Leung; Ennis, Dawn; Khurshid, Nazish; Lambert, Kelly; Machhar, Rohan; Meisuria, Mitul; Osman, A. E.; Peat, Irene M; Sahota, Harjinder; Woodings, Pamela; Talbot, Chris J.; Symonds, R. Paul

doi:10.1016/j.ijrobp.2012.02.018

Cited by 20 publications

(16 citation statements)

References 23 publications

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“…18 studies were identified to investigate the rs1801516 polymorphism and the risk of developing late adverse events. After further exclusion of studies with nonextractable data (n = 2) and studies on late adverse events other than fibrosis (n = 8), 8 published studies 5,10,11,23–27 were identified to meet the inclusion criteria. In addition, 1 study 28 was identified from the references of a review article.…”

Section: Resultsmentioning

confidence: 99%

“…3 out of 9 studies were conducted in the United States, 5,24,28 2 in United Kingdom, 10,11 1 in Switzerland, 25 1 in Saudi Arabia, 26 1 in Brazil, 27 and 1 in Germany. 23 None of these studies stated the ethnicity of the participants (therefore, an assessment of the effects of population stratification was not conducted in the subsequent analyses).…”

Section: Resultsmentioning

confidence: 99%

“…5,25 The number of patients within each grade was given in 2 studies. 11,28 Therefore, a grade 2 cut-off was set for differentiating cases from controls in this meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Another concern for this meta-analysis was an incomplete coverage of studies, including some large studies with appropriate statistical power. 10,11 It is thus unclear whether there is a role of the rs1801516 polymorphism in the development of radiotherapy-induced adverse events. We have found that late fibrosis was the most frequently studied late adverse events (data unpublished).…”

Section: Introductionmentioning

confidence: 99%

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Single Nucleotide Polymorphism rs1801516 in Ataxia Telangiectasia-Mutated Gene Predicts Late Fibrosis in Cancer Patients After Radiotherapy

et al. 2016

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Studies on associations between ataxia telangiectasia-mutated (ATM) polymorphisms and late radiotherapy-induced adverse events vary in clinical settings, and the results are inconsistent.We conducted the first meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to investigate the role of the ATM polymorphism rs1801516 in the development of radiotherapy-induced late fibrosis.We searched PubMed, Embase, Web of Science, and Chinese National Knowledge Infrastructure databases to identify studies that investigated the effect of the ATM polymorphism rs1801516 on radiotherapy-induced late fibrosis before September 8, 2015. Summary odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were used to assess the association between late fibrosis and the rs1801516 polymorphism. Subgroup analyses were conducted to evaluate the influence of clinical features on the genetic association. Tests of interaction were used to compare differences in the effect estimates between subgroups.The overall meta-analysis of 2000 patients from 9 studies showed that the minor allele of the rs1801516 polymorphism was associated with a significantly increased risk of developing late fibrosis (OR = 1.78, 95% CI: 1.07, 2.94), with high between-study heterogeneity (I2 = 66.6%, P = 0.002). In subgroup analyses, we identified that the incidence of late fibrosis was a major source of heterogeneity across studies. The OR for patients with a high incidence of late fibrosis was 3.19 (95% CI: 1.86, 5.47), in contrast to 1.09 (95% CI: 1.01, 1.17) for those with a low incidence. There was a significant difference in the effect estimates between the 2 subgroups (ratio of OR = 2.94, 95% CI 1.70, 5.08, P = 0.031).This meta-analysis supported previously reported effect of the ATM polymorphism rs1801516 on radiotherapy-induced late fibrosis. This finding encouraged further researches to identify more genetic polymorphisms that were predictive for radiotherapy-induced adverse events. In addition, we showed that the inconsistency of the associations seen in these studies might be related to variations in the incidence of late fibrosis in the patients. This suggested that future studies should consider the incidence of radiotherapy-induced adverse events when investigating radiosensitivity signature genes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…5,25 The number of patients within each grade was given in 2 studies. 11,28 Therefore, a grade 2 cut-off was set for differentiating cases from controls in this meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Single Nucleotide Polymorphism rs1801516 in Ataxia Telangiectasia-Mutated Gene Predicts Late Fibrosis in Cancer Patients After Radiotherapy

et al. 2016

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“…Another consideration is that racial/ethnic differences in EASRs may be attributed to multiple genetic risk factors. For example, previous studies have shown that racial/ethnic differences in RT-induced skin reactions in ATM sequence variant carriers: 17% Hispanics, 23% African Americans and 8% Whites (9, 28). Therefore, future large genetic studies are warranted to elucidate contribution of genetic variants in racial/ethnic differences of RT-induced EASRs and late effects.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in Patients with Breast Cancer

Rodriguez-Gil

Takita

Wright

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Post-surgery adjuvant radiotherapy (RT) significantly reduced the local recurrence rate. However, many patients develop early adverse skin reactions (EASRs) that impact quality of life and treatment outcomes. Methods We evaluated an inflammatory biomarker, C-reactive protein (CRP) in predicting RT-induced EASRs in 159 breast cancer patients undergoing RT. In each patient, we measured pre- and post-RT plasma CRP levels using a highly-sensitive ELISA CRP assay. RT-induced EASRs were assessed at weeks 3 and 6 using the National Cancer Institute Common Toxicity Criteria (v3.0). Association between EASRs and CRP levels were assessed using logistic regression models after adjusting for potential confounders. Results RT-induced grade 2+ EASRs were observed in 8 (5%) and 80 (50%) patients at weeks 3 and 6 (end of RT), respectively. At the end of RT, significantly higher proportion of African Americans developed grade 3 EASRs (13.8% vs. 2.3% in others); grade 2+ EASRs were significantly associated with: change of CRP>1 mg/L (OR=2.51; 95%CI=1.06, 5.95, p=0.04), obesity (OR=2.08; 95%CI=1.03, 4.21, p=0.04), or combined both factors (OR=5.21; 95%CI=1.77, 15.38, p=0.003). Conclusion This is the first study to demonstrate that an inflammatory biomarker CRP is associated with RT-induced EASRs, particularly combined with obesity. Impact Future larger studies are warranted to validate our findings and facilitate the discovery and development of anti-inflammatory agents to protect normal tissue from RT-induced adverse effects and improve quality of life in breast cancer patients undergoing RT.

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Genetic susceptibility to cutaneous radiation injury

Huang

Glick

2016

Arch Dermatol Res

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The use of ionizing radiation is critical to cancer treatment and fluoroscopic procedures. However, despite efforts to minimize total radiation dose, many patients experience toxic cutaneous side-effects of ionizing radiation, ranging from mild erythema to subcutaneous fibrosis, telangiectasia formation, and ulceration. Extent of injury is highly variable among patients. Studying the genetic determinants of radiation injury can help develop protocols to reduce radiation toxicity, as well as drive research into effective modulators of the genes and gene products associated with radiation injury. Many studies in the past two decades have identified single-nucleotide polymorphisms that may be associated with susceptibility to cutaneous radiation injury, such as those in genes related to the following cellular responses to ionizing radiation: inflammation, DNA repair, oxidation and stress response, and cell-cycle and apoptosis. This review summarizes the current literature on potential major genes and polymorphisms, in the previously described damage response pathways, that are involved in susceptibility to cutaneous radiation injury. Potential pitfalls of current research and further avenues of discovery will be explored.

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Variation in Telangiectasia Predisposing Genes Is Associated With Overall Radiation Toxicity

Cited by 20 publications

References 23 publications

Single Nucleotide Polymorphism rs1801516 in Ataxia Telangiectasia-Mutated Gene Predicts Late Fibrosis in Cancer Patients After Radiotherapy

Single Nucleotide Polymorphism rs1801516 in Ataxia Telangiectasia-Mutated Gene Predicts Late Fibrosis in Cancer Patients After Radiotherapy

Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in Patients with Breast Cancer

Genetic susceptibility to cutaneous radiation injury

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