Impact of VEGF gene polymorphisms and haplotypes on radiation-induced late toxicity in prostate cancer patients

Langsenlehner, Tanja; Renner, Wilfried; Gerger, Armin; Hofmann, Gunter; Thurner, E.M.; Kapp, Karin S.; Langsenlehner, Uwe

doi:10.1007/s00066-011-1106-4

Cited by 14 publications

(4 citation statements)

References 51 publications

(60 reference statements)

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“…On the contrary, a higher frequency of the II genotype and I allele of 18 bp I/D VEGF was found in patients with breast cancer in comparison to healthy individuals (21). This polymorphism was reported to be in complete linkage with single nucleotide polymorphism −2578 VEGF and individuals with the −2578A allele have an insertion of 18 bp (19,22). We observed similar results in our study.…”

Section: Discussionsupporting

confidence: 90%

Associations Between Gene Polymorphisms of Vascular Endothelial Growth Factor and Prostate Cancer

et al. 2019

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Background/Aim: The aim of this study was to evaluate the association between selected polymorphisms of the vascular endothelial growth factor gene (rs699947, rs144854329, rs833061, rs2010963, rs3025039) and the risk of prostate cancer development and progression. Materials and Methods: The present study included 446 patients with prostate cancer and 241 healthy men. Genotyping was performed by polymerase-chain reaction-restriction fragment length polymorphism analysis. Results: No significant association between the individual polymorphisms studied and the risk of prostate cancer development was detected. A statistically significantly increased risk of prostate cancer development associated with the presence of 9 or 10 risky alleles was found considering the whole group of patients, as well as in patients with low-grade carcinomas (Gleason score <7). Conclusion: Individual polymorphisms of VEGF do not appear to contribute to prostate cancer. However, a combination of risky alleles of the studied polymorphisms significantly increases the risk of prostate cancer in Slovak patients.

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Section: Discussionsupporting

confidence: 90%

Associations Between Gene Polymorphisms of Vascular Endothelial Growth Factor and Prostate Cancer

et al. 2019

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“…This has further been associated with interstitial hypertension and reduced blood flow, both features that contribute to hypoxic and acidic microenvironments that perpetuate a non-healing tissue response causing a secondary cycle of damage [42,43]. Some genetic variants in the VEGFA gene may influence the risk of high-grade late rectal toxicity after radiotherapy for prostate cancer [25]. We have previously seen an increase in both hypoxia and VEGFA gene expression patterns in both radiated adipose and vascular tissue from BC and HNC patients, respectively [44,45], but have never studied genetic variants related to this biology.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the analyses of plasma proteins, we analyzed 55 SNPs in both study sets by DNA genotyping of 31 genes that were reported in the literature to be involved in RS [23][24][25][26][27][28][29]. Among these, we found corresponding protein profiles for 8 genes from which only VEGFA was found significant in univariate analysis of the proteins, but without correction for multiple testing (Table S3).…”

Section: Patient Genotype and Its Association With Radiosensitivitymentioning

confidence: 99%

Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer

Drobin

Marczyk

Halle

et al. 2020

Cancers

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Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear during or long time after finishing radiotherapy and depend on the patient’s radiosensitivity. Currently, there is no assay available that can reliably predict the individual’s response to radiotherapy. We profiled two study sets from breast (n = 29) and head-and-neck cancer patients (n = 74) that included radiosensitive patients and matched radioresistant controls.. We studied 55 single nucleotide polymorphisms (SNPs) in 33 genes by DNA genotyping and 130 circulating proteins by affinity-based plasma proteomics. In both study sets, we discovered several plasma proteins with the predictive power to find radiosensitive patients (adjusted p < 0.05) and validated the two most predictive proteins (THPO and STIM1) by sandwich immunoassays. By integrating genotypic and proteomic data into an analysis model, it was found that the proteins CHIT1, PDGFB, PNKD, RP2, SERPINC1, SLC4A, STIM1, and THPO, as well as the VEGFA gene variant rs69947, predicted radiosensitivity of our breast cancer (AUC = 0.76) and head-and-neck cancer (AUC = 0.89) patients. In conclusion, circulating proteins and a SNP variant of VEGFA suggest that processes such as vascular growth capacity, immune response, DNA repair and oxidative stress/hypoxia may be involved in an individual’s risk of experiencing radiation-induced toxicity.

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“…The criticality of VEGF-α to carcinogenesis has been reviewed in detail elsewhere67. Photons, such as gamma rays, have been shown to increase VEGF-α and subsequent tumor initiation and/or progression6869. Likewise, high-LET radiation such as carbon ion radiation has been shown to induce transcription and translation of VEGF-α in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

High Energy Particle Radiation-associated Oncogenic Transformation in Normal Mice: Insight into the Connection between Activation of Oncotargets and Oncogene Addiction

Aravindan

Krishnan

et al. 2016

Sci Rep

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Concerns on high-energy particle radiation-induced tumorigenic transformation of normal tissue in astronauts, and in cancer patients undergoing radiotherapy, emphasizes the significance of elucidating the mechanisms involved in radiogenic transformation processes. Mostly used genetically modified or tumor-prone models are less reliable in determining human health risk in space or protracted post-treatment normal tissue toxicity. Here, in wild type C57BL/6 mice, we related the deregulation of distinctive set of tissue-specific oncotargets in major organs upon 56Fe (600 MeV/amu; 0.5 Gy/min; 0.8 Gy) particle radiation and compared the response with low LET γ-radiation (137Cs; 0.5 Gy/min; 2 Gy). One of the novel findings is the ‘tissue-independent’ activation of TAL2 upon high-energy radiation, and thus qualifies TAL2 as a potential biomarker for particle and other qualities of radiation. Heightened expression of TAL2 gene transcript, which sustained over four weeks post-irradiation foster the concept of oncogene addiction signaling in radiogenic transformation. The positive/negative expression of other selected oncotargets that expresses tissue-dependent manner indicated their role as a secondary driving force that addresses the diversity of tissue-dependent characteristics of tumorigenesis. This study, while reporting novel findings on radiogenic transformation of normal tissue when exposed to particle radiation, it also provides a platform for further investigation into different radiation quality, LET and dose/dose rate effect in healthy organs.

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Impact of VEGF gene polymorphisms and haplotypes on radiation-induced late toxicity in prostate cancer patients

Abstract: We conclude that genetic variants in the VEGF gene may influence the risk of high-grade late rectal toxicity after definitive radiotherapy for prostate cancer.

Cited by 14 publications

References 51 publications

Associations Between Gene Polymorphisms of Vascular Endothelial Growth Factor and Prostate Cancer

Associations Between Gene Polymorphisms of Vascular Endothelial Growth Factor and Prostate Cancer

Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer

High Energy Particle Radiation-associated Oncogenic Transformation in Normal Mice: Insight into the Connection between Activation of Oncotargets and Oncogene Addiction

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