No association between TGF-β1 polymorphisms and radiation-induced lung toxicity in a European cohort of lung cancer patients

Voets, A.M.; Oberije, Cary; Struijk, Robert B.; Reymen, Bart; Ruyck, Kim De; Thierens, Hubert; Vandecasteele, Katrien; Neve, Wilfried De; Houben, Ruud; Ruysscher, Dirk De; Smeets, Hubert J.M.; Lambin, Philippe

doi:10.1016/j.radonc.2012.09.016

Cited by 26 publications

(19 citation statements)

References 19 publications

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“…-1552delAGG/-509C>T/L10P TGFB1 compound homozygotes BMI = body mass index CHT = chemotherapy PALU -paraaortic EBRT Our observation that single nucleotide polymorphism of TGFB1 does not correlate with normal tissue radiosensitivity corresponds with results of recent studies [20,21]. We think that the finding the statistically significant relationship between compound homozygosity and late complications, even in the small patients group, is interesting and deserves further evaluation.…”

supporting

confidence: 83%

ATM and TGFB1 genes polymorphisms in prediction of late complications of chemoradiotherapy in patients with locally advanced cervical cancer

Paulíková¹,

Petera²,

Sirák³

et al. 2014

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The purpose of our study was to evaluate a possible correlation between genetic polymorphisms in ATM and TGFB1 genes and late toxicity of chemoradiotherapy for locally advanced cervical cancer. Fifty five patients with FIGO stage IIB and higher without a disease recurrence with a mean follow up of 6 years were included. Late toxicity was assessed by EORTC/RTOG late toxicity criteria. Univariate and multivariate logistic regression model was used for statistical analysis. Degree of association between polymorphisms and late toxicity of chemotherapy was assessed on the basis of phi-coefficient (φ) as well. We did not find any association between 5557G>A polymorphism in the ATM gene or single TGFB1 polymorphisms and late toxicity. TGFB1 compound homozygosity (-1552delAGG, -509C>T, L10P) was a significant predictive factor of grade III-IV and any grade of complications in both univariate and multivariate logistic regression analyses and statistical significance of association between polymorphisms and late toxicity of chemoradiotherapy was confirmed also by the evaluation of phi-coefficient (φ). We conclude that haplotypes instead of single nucleotide polymorphic sites in the genes may better characterize the individual radiosensitivity.

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supporting

confidence: 83%

ATM and TGFB1 genes polymorphisms in prediction of late complications of chemoradiotherapy in patients with locally advanced cervical cancer

Paulíková¹,

Petera²,

Sirák³

et al. 2014

neo

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“…Subsequent larger validation studies and meta-analyses were unable to confirm associations between breast shrinkage and SNPs in TGFB1 and various other genes (36, 72-74). Similarly, TGFB1 polymorphisms were not significantly associated with radiation-induced lung toxicity (pneumonitis) in two of three studies on lung cancer patients (75-77). However, a significant association was found between a SNP in the TNF promoter and combined late reactions (telangiectasia and fibrosis) using the standardized total average toxicity (STAT) score (78) and pooling a discovery and three replication cohorts (79).…”

Section: ‘Omics’ Approachesmentioning

confidence: 94%

Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?

et al. 2016

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Adverse reactions in normal tissue after radiotherapy (RT) limit the dose that can be given to tumour cells. Since 80% of individual variation in clinical response is estimated to be caused by patient-related factors, identifying these factors might allow prediction of patients with increased risk of developing severe reactions. While inactivation of cell renewal is considered a major cause of toxicity in early-reacting normal tissues, complex interactions involving multiple cell types, cytokines, and hypoxia seem important for late reactions. Here, we review ‘omics’ approaches such as screening of genetic polymorphisms or gene expression analysis, and assess the potential of epigenetic factors, posttranslational modification, signal transduction, and metabolism. Furthermore, functional assays have suggested possible associations with clinical risk of adverse reaction. Pathway analysis incorporating different ‘omics’ approaches may be more efficient in identifying critical pathways than pathway analysis based on single ‘omics’ data sets. Integrating these pathways with functional assays may be powerful in identifying multiple subgroups of RT patients characterized by different mechanisms. Thus ‘omics’ and functional approaches may synergize if they are integrated into radiogenomics ‘systems biology’ to facilitate the goal of individualised radiotherapy.

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“…Associations between the TGFβ1 869C/T polymorphism and susceptibility to radiation pneumonitis have been documented earlier (95, 96). A comprehensive meta-analysis in this regard reports that there was a significant association between TGFβ1 869C/T polymorphism and RP susceptibility (OR = 1.77; 95% CI, 1.27–2.47; p = 0.0007).…”

Section: Current Treatment Strategiesmentioning

confidence: 70%

Immunological Aspect of Radiation-Induced Pneumonitis, Current Treatment Strategies, and Future Prospects

et al. 2017

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Delivery of high doses of radiation to thoracic region, particularly with non-small cell lung cancer patients, becomes difficult due to subsequent complications arising in the lungs of the patient. Radiation-induced pneumonitis is an early event evident in most radiation exposed patients observed within 2–4 months of treatment and leading to fibrosis later. Several cytokines and inflammatory molecules interplay in the vicinity of the tissue developing radiation injury leading to pneumonitis and fibrosis. While certain cytokines may be exploited as biomarkers, they also appear to be a potent target of intervention at transcriptional level. Initiation and progression of pneumonitis and fibrosis thus are dynamic processes arising after few months to year after irradiation of the lung tissue. Currently, available treatment strategies are challenged by the major dose limiting complications that curtails success of the treatment as well as well being of the patient’s future life. Several approaches have been in practice while many other are still being explored to overcome such complications. The current review gives a brief account of the immunological aspects, existing management practices, and suggests possible futuristic approaches.

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No association between TGF-β1 polymorphisms and radiation-induced lung toxicity in a European cohort of lung cancer patients

Cited by 26 publications

References 19 publications

ATM and TGFB1 genes polymorphisms in prediction of late complications of chemoradiotherapy in patients with locally advanced cervical cancer

ATM and TGFB1 genes polymorphisms in prediction of late complications of chemoradiotherapy in patients with locally advanced cervical cancer

Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?

Immunological Aspect of Radiation-Induced Pneumonitis, Current Treatment Strategies, and Future Prospects

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