Meta-analysis of Associations between ATM Asp1853Asn and TP53 Arg72Pro Polymorphisms and Adverse Effects of Cancer Radiotherapy

Su, Meng; Yin, Zhihua; Wu, Wei; Li, Xuelian; Zhou, Baosen

doi:10.7314/apjcp.2014.15.24.10675

Cited by 12 publications

(12 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect size of the rs1801516 SNP demonstrated by our meta-analysis is below the detectable effect size in the radio-genomics GWASs published so far (2–8). Furthermore, the small effect size explains why the candidate gene studies conducted did not report consistent findings for this SNP [19–21]. As mentioned in the introduction, three literature based meta-analyses have addressed the impact of the rs1801516 SNP upon risk of normal tissue toxicity after radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…This SNP results in a non-conservative amino acid substitution from an aspartic acid to an asparagine in exon 37 (NM_000051.3). A number of relatively small studies indicated that the minor allele of this SNP increases the risk of normal tissue toxicity after radiotherapy (reviewed in [19–21]). Nevertheless, the findings have not been entirely consistent.…”

mentioning

confidence: 99%

“…Three literature based meta-analyses have addressed the impact of the rs1801516 SNP upon radiation-induced normal tissue toxicity. Two of these meta-analyses demonstrated a significantly increased risk of acute toxicity ( N = 1588) [20] and radiation-induced fibrosis ( N = 2000) [21] respectively among carriers of the minor (Asn) allele whereas the largest of these meta-analyses ( N = 2127) did not show a significant association between the SNP and risk of normal tissue toxicity in broader terms [19]. In order to bring this SNP to a test in the setting of a well-powered investigation, the International Radio-genomics Consortium (RgC) [22] conducted an individual patient data meta-analysis.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients

Andreassen

Rosenstein

Kerns

et al. 2016

Radiotherapy and Oncology

100

View full text Add to dashboard Cite

Purpose Several small studies have indicated that the ATM rs1801516 SNP is associated with risk of normal tissue toxicity after radiotherapy. However, the findings have not been consistent. In order to test this SNP in a well-powered study, an individual patient data meta-analysis was carried out by the International Radiogenomics Consortium. Materials and methods The analysis included 5456 patients from 17 different cohorts. 2759 patients were given radiotherapy for breast cancer and 2697 for prostate cancer. Eight toxicity scores (overall toxicity, acute toxicity, late toxicity, acute skin toxicity, acute rectal toxicity, telangiectasia, fibrosis and late rectal toxicity) were analyzed. Adjustments were made for treatment and patient related factors with potential impact on the risk of toxicity. Results For all endpoints except late rectal toxicity, a significantly increased risk of toxicity was found for carriers of the minor (Asn) allele with odds ratios of approximately 1.5 for acute toxicity and 1.2 for late toxicity. The results were consistent with a co-dominant pattern of inheritance. Conclusion This study convincingly showed a significant association between the ATM rs1801516 Asn allele and increased risk of radiation-induced normal tissue toxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients

Andreassen

Rosenstein

Kerns

et al. 2016

Radiotherapy and Oncology

100

View full text Add to dashboard Cite

show abstract

“…5 The functional impact of this polymorphism is unclear. 5 A recent meta-analysis 9 showed no significant association between the rs1801516 polymorphism and radiotherapy-induced adverse events in general. However, the studied adverse events included a variety of different clinical endpoints, involving a variety of different pathological mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

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.

show abstract

“…The discovery and introduction of anticancer drugs targeting molecules involved in the cell-cycle and checkpoint regulation, such as cell-cycle or checkpoint inhibitors 171 , can also influence ATM indirectly. The majority of cancer therapy studies related to ATM have focused on its significance in radiotherapy 172-175 . Molecular mechanisms that cause resistance to radiotherapy in glioma cells have been linked to the expression of ATM, in cooperation with other pro-survival networks 176 .…”

Section: Therapeutic Opportunitiesmentioning

confidence: 99%

ATM in breast and brain tumors: a comprehensive review

Estiar

Mehdipour

2018

Cancer Biology & Medicine

View full text Add to dashboard Cite

The ATM gene is mutated in the syndrome, ataxia-telangiectasia (AT), which is characterized by predisposition to cancer. Patients with AT have an elevated risk of breast and brain tumors Carrying mutations in ATM, patients with AT have an elevated risk of breast and brain tumors. An increased frequency of ATM mutations has also been reported in patients with breast and brain tumors; however, the magnitude of this risk remains uncertain. With the exception of a few common mutations, the spectrum of ATM alterations is heterogeneous in diverse populations, and appears to be remarkably dependent on the ethnicity of patients. This review aims to provide an easily accessible summary of common variants in different populations which could be useful in ATM screening programs. In addition, we have summarized previous research on ATM, including its molecular functions. We attempt to demonstrate the signiﬁcance of ATM in exploration of breast and brain tumors and its potential as a therapeutic target.

show abstract

Meta-analysis of Associations between ATM Asp1853Asn and TP53 Arg72Pro Polymorphisms and Adverse Effects of Cancer Radiotherapy

Cited by 12 publications

References 32 publications

Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients

Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients

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

ATM in breast and brain tumors: a comprehensive review

Contact Info

Product

Resources

About