Does variability in normal tissue reactions after radiotherapy have a genetic basis – where and how to look for it?

Andreassen, Christian Nicolaj; Alsner, Jan; Overgaard, Jens

doi:10.1016/s0167-8140(02)00154-8

Cited by 172 publications

(117 citation statements)

References 85 publications

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“…For about one third of the irradiated cancer patients, differences in dose volume metrics (e.g., tumour dose, fractionation scheme), additional treatment modalities (chemotherapy, surgery) and patient specific factors (e.g., age, gender, comorbidities) are the main contributors to the development of adverse reactions. For the majority of the cases, variation in intrinsic genetic determinants are responsible for the normal tissue toxicities (5).…”

Section: Introductionmentioning

confidence: 99%

Prediction of late normal tissue complications in RT treated gynaecological cancer patients: Potential of the γ-H2AX foci assay and association with chromosomal radiosensitivity

Werbrouck

Ruyck²,

Beels³

et al. 2009

Oncol Rep

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Abstract. In the present study, the Á-H2AX assay was investigated as a predictive test for the development of late normal tissue complications. Therefore, phosphorylated histone H2AX (Á-H2AX) foci were scored in peripheral blood T-lymphocytes of gynaecological radiotherapy patients, irradiated in vitro with a high dose rate (HDR) and a low dose rate (LDR) protocol. The G 2 chromatid break assay was used to compare chromosomal radiation sensitivity with DNA doublestrand-break (DSB) repair capacity. Late normal tissue reactions were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 scale. In our analyses, no differences in foci kinetics were found between the non to mild and moderate to severe patient groups after HDR irradiation. Furthermore, no relation was observed between the level of residual Á-H2AX foci and CTC score after LDR irradiation. On the contrary, the number of chromatid breaks was associated with late clinical radiation sensitivity. Comparison of G 2 chromatid break assay data with the residual number of radiationinduced foci after LDR irradiation and repair times after HDR irradiation showed no relationship between the assays. From this study we can conclude that scoring of Á-H2AX foci after in vitro irradiation of isolated T-lymphocytes of patients is not predictive for late radiotoxicity. This applies as well to the assessment of the repair kinetics after an HDR dose as to the determination of the number of residual foci after a LDR dose.

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Section: Introductionmentioning

confidence: 99%

Prediction of late normal tissue complications in RT treated gynaecological cancer patients: Potential of the γ-H2AX foci assay and association with chromosomal radiosensitivity

Werbrouck

Ruyck²,

Beels³

et al. 2009

Oncol Rep

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show abstract

“…Clinical sensitivity to ionizing radiation varies considerably among patients, and radiation-induced adverse effects developing in normal tissue can be therapy limiting in >10% of patients (1). Ionizing radiation induces both DNA singlestrand breaks and double-strand breaks (DSB), with the DSBs generally considered the lethal event (2).…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphisms in the DNA Double-Strand Break Repair Genes XRCC3, XRCC2, and NBS1 Are Not Associated with Acute Side Effects of Radiotherapy in Breast Cancer Patients

Popanda

Tan

Ambrosone

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Currently, increasing efforts are made to investigate whether clinical normal tissue radiosensitivity is influenced by genetic germline variation [1,6]. A recently published study, based on a cohort of 41 Danish breast cancer patients given post-mastectomy radiotherapy, has indicated a possible association between selected single nucleotide polymorphisms (SNPs) and the risk of subcutaneous fibrosis after radiotherapy [2].…”

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confidence: 99%

TGFB1 polymorphisms are associated with risk of late normal tissue complications in the breast after radiotherapy for early breast cancer

Andreassen

Alsner

Overgaard

et al. 2005

Radiotherapy and Oncology

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129

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Recent studies suggest that normal tissue radiosensitivity is influenced by single nucleotide polymorphisms (SNPs) in certain genes. In order to seek a confirmation of these findings, this study investigated SNPs in genes TGFB1 (position K509, codon 10 and codon 25), SOD2 (codon 16), XRCC1 (codon 399), XRCC3 (codon 241), APEX (codon 148) and ATM (codon 1853) in 26 breast cancer patients with marked changes in breast appearance after radiotherapy and 26 matched controls. Statistically significant associations were found between the TGFB1 codon 10 Pro allele (PZ0.005) as well as the TGFB1 position K509 T allele (PZ 0.018) and increased risk of altered breast appearance. No significant associations were found for the remaining SNPs.

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Does variability in normal tissue reactions after radiotherapy have a genetic basis – where and how to look for it?

Cited by 172 publications

References 85 publications

Prediction of late normal tissue complications in RT treated gynaecological cancer patients: Potential of the γ-H2AX foci assay and association with chromosomal radiosensitivity

Prediction of late normal tissue complications in RT treated gynaecological cancer patients: Potential of the γ-H2AX foci assay and association with chromosomal radiosensitivity

Genetic Polymorphisms in the DNA Double-Strand Break Repair Genes XRCC3, XRCC2, and NBS1 Are Not Associated with Acute Side Effects of Radiotherapy in Breast Cancer Patients

TGFB1 polymorphisms are associated with risk of late normal tissue complications in the breast after radiotherapy for early breast cancer

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