Genetic factors in individual radiation sensitivity

Hornhardt, Sabine; Rößler, Ute; Sauter, Wiebke; Rosenberger, Albert; Illig, Thomas; Bickeböller, Heike; Wichmann, H.E.; Gomolka, Maria

doi:10.1016/j.dnarep.2014.02.001

Cited by 39 publications

(23 citation statements)

References 65 publications

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“…We found a significant difference between healthy controls and early onset lung cancer patients with respect to DNA repair capacity in a separate and independent case control study applying an identical comet assay protocol [30]. These data support the hypothesis that impaired repair capacity is also detectable in our patient cohort, may be due to genetic factors.…”

Section: Resultssupporting

confidence: 83%

Heritability of Radiation Response in Lung Cancer Families

Rosenberger

Rößler

Hornhardt

et al. 2012

Genes

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Radiation sensitivity is assumed to be a cancer susceptibility factor due to impaired DNA damage signalling and repair. Relevant genetic factors may also determine the observed familial aggregation of early onset lung cancer. We investigated the heritability of radiation sensitivity in families of 177 Caucasian cases of early onset lung cancer. In total 798 individuals were characterized for their radiation-induced DNA damage response. DNA damage analysis was performed by alkaline comet assay before and after in vitro irradiation of isolated lymphocytes. The cells were exposed to a dose of 4 Gy and allowed to repair induced DNA-damage up to 60 minutes. The primary outcome parameter Olive Tail Moment was the basis for heritability estimates. Heritability was highest for basal damage (without irradiation) 70% (95%-CI: 51%–88%) and initial damage (directly after irradiation) 65% (95%-CI: 47%–83%) and decreased to 20%–48% for the residual damage after different repair times. Hence our study supports the hypothesis that genomic instability represented by the basal DNA damage as well as radiation induced and repaired damage is highly heritable. Genes influencing genome instability and DNA repair are therefore of major interest for the etiology of lung cancer in the young. The comet assay represents a proper tool to investigate heritability of the radiation sensitive phenotype. Our results are in good agreement with other mutagen sensitivity assays.

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Section: Resultssupporting

confidence: 83%

Heritability of Radiation Response in Lung Cancer Families

Rosenberger

Rößler

Hornhardt

et al. 2012

Genes

Self Cite

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“…However, sample size was smaller and follow-up time of only 2 years was shorter compared to our data, and photographic assessment tools were used. On the other hand, rs3213334 was recently shown to be associated with basal DNA damage levels in lymphocytes of lung cancer patients (vs. cancer-free controls), assessed by comet assay technology (29). In addition, XRCC1 polymorphisms were clearly correlated with in vitro radiosensitivity in the lung cancer patients.…”

Section: Page 10 Of 17mentioning

confidence: 99%

XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients

Seibold

Behrens

Schmezer

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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“…Radioresistance is a common issue that results in treatment failure, and it has been reported that radioresistance is mediated by tumor-related genes affecting cellular processes (38,39). A number of factors are associated with cancer risk and radiosensitivity, including alterations in DNA repair, cell cycle or apoptotic pathways (40). Previous evidence has revealed that the downregulation of MTDH can reduce the viability, colony formation and invasion of U87 human glioma cells and 9L rat gliosarcoma cells (41,42).…”

Section: Discussionmentioning

confidence: 99%

Silencing the expression of MTDH increases the radiation sensitivity of SKOV3 ovarian cancer cells and reduces their proliferation and metastasis

Jia

Zhu

et al. 2018

Int J Oncol

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Ovarian cancer has a high mortality rate among women worldwide. Radiotherapy is considered an effective method of ovarian cancer treatment, however, radioresistance presents a challenge. It is necessary to develop techniques that can increase radiosensitivity in ovarian cancer, and gene therapy is a promising option. The aim of the present study was to investigate the effects of metadherin (MTDH) silencing on the radiosensitivity of ovarian cancer. Ovarian cancer tissues (n=273) and normal ovarian tissues (n=277) were used, as were SKOV3 ovarian cancer cells and the immortalized human ovarian epidermal HOSEpiC cell line. MTT, Transwell and wound-healing assays were performed to assess the proliferation, invasion and migration abilities of the SKOV3 cells. Colony-forming assays and flow cytometry were applied to detect the radiosensitivity and apoptosis of the SKOV3 cells. Nude mouse xenograft models were established to evaluate the effect of MTDH gene silencing on tumor growth and the efficacy of radiotherapy. Ovarian cancer, in tissues and cells, was demonstrated to have a high level of MTDH. Additionally, MTDH silencing was found to significantly inhibit proliferation, migration and invasion, and induce apoptosis in SKOV3 cells, and it was suggested that MTDH depletion significantly increased the sensitivity of the SKOV3 cells to X-ray radiation. MTDH silencing enhanced radiosensitivity and delayed tumor growth in the nude mouse xenograft model. Collectively, the results obtained in the present study suggest the potential role of MTDH silencing as a technique for ameliorating radioresistance in ovarian cancer. The present study provides a promising experimental basis for the improvement of ovarian cancer radiotherapy treatment.

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Genetic factors in individual radiation sensitivity

Cited by 39 publications

References 65 publications

Heritability of Radiation Response in Lung Cancer Families

Heritability of Radiation Response in Lung Cancer Families

XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients

Silencing the expression of MTDH increases the radiation sensitivity of SKOV3 ovarian cancer cells and reduces their proliferation and metastasis

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