G0 and G2 Chromosomal Assays in the Evaluation of Radiosensitivity in a Cohort of Italian Breast Cancer Patients

Poggioli, Tommaso; Sterpone, Silvia; Palma, Selena; Cozzi, Renata; Testa, Antonella

doi:10.1269/jrr.10052

Cited by 8 publications

(5 citation statements)

References 27 publications

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“…In our study, 89% of the patients were radiosensitive or highly radiosensitive, 11% of the patients had normal IRS and no patient was radioresistant (Table 1). The proportion of increased radiosensitive patients (89%) in this study is larger compared with numbers reported by other authors [20][21][22].…”

Section: Discussioncontrasting

confidence: 69%

Individual Radiosensitivity as a Risk Factor for the Radiation-Induced Acute Radiodermatitis

Kišonas

Venius

Sevriukova

et al. 2021

Life

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Background: Up to 95% of irradiated patients suffer from ionizing radiation (IR) induced early skin reaction, acute radiation dermatitis (ARD). Some experts think that additional skin hydration can reduce acute skin reactions. Individual radiosensitivity (IRS) determined from lymphocytes may help to predict acute radiation toxicity. The purpose of this study is to evaluate the clinical manifestation of ARD in different skincare groups during whole breast radiotherapy depending on IRS and other risk factors. Methods: A total of 108 early-stage breast cancer patients were randomized into best supportive care (BSC) and additional skincare (ASC) groups. IRS was evaluated using a G2 assay modified with caffeine-induced G2 checkpoint arrest. All patients received a 50 Gy dose to the breast planning target volume (PTV). Clinical assessment of ARD symptoms according to the CTCAE grading scale was performed once a week. Results: IRS was successfully determined for 91 out of 108 patients. A total of 10 patients (11%) had normal IRS, 47 patients (52%) were categorized as radiosensitive, and 34 (37%) as highly radiosensitive. There was no significant difference in the manifestation of ARD between patient groups by skincare or IRS. According to logistic regression, patients with bigger breasts were prone to more severe ARD (p = 0.002). Conclusions: The additional skincare did not improve skin condition during RT. A total of 89% of patients had increased radiosensitivity. IRS determined before RT did not show the predictive value for the manifestation of ARD. Logistic regression revealed that breast volume was the most significant risk factor for the manifestation of ARD.

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Section: Discussioncontrasting

confidence: 69%

Individual Radiosensitivity as a Risk Factor for the Radiation-Induced Acute Radiodermatitis

Kišonas

Venius

Sevriukova

et al. 2021

Life

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“…Increased G 2 chromosomal radiosensitivity of peripheral blood lymphocytes has been associated with a number of common sporadic cancers including breast (1)(2)(3)(4)(5)(6)(7)(8)(9), colorectal (5), prostrate (10), head and neck (11,12) and a range of early-onset cancers (13) and heritability of the radiosensitive phenotype has been demonstrated (4,(14)(15)(16)(17). These observations suggest that G 2 chromosomal radiosensitivity may be a marker of inherited low penetrance cancer predisposition genes (3,5,8,18,19).…”

Section: Introductionmentioning

confidence: 91%

Intra-individual variation in G2 chromosomal radiosensitivity

Curwen¹,

Cadwell²,

Tawn

et al. 2012

Mutagenesis

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Intra-individual variation in G(2) chromosomal radiosensitivity was examined by repeatedly taking blood samples from two individuals. Two healthy female volunteers provided a total of 44 blood samples, Donor 1 gave 28 samples in four time periods between 2001 and 2006 and Donor 2 gave 16 samples in two of the same time periods. Lymphocytes were cultured for 72 h prior to irradiation with 0.5 Gy, 300 kV X-rays. Colcemid was added 30 min post-irradiation. Cultures were harvested 90 min post-irradiation and analysed for chromatid gaps and breaks. Donor 1 exhibited significant intra-individual variation in G(2) chromosomal radiosensitivity for two of the four time periods. Variation was not significant for Period 1 (13 samples, P = 0.111) and Period 2 (six samples, P = 0.311) but was significant for Period 3 (two samples, P = 0.030) and Period 4 (seven samples, P = 0.005). Significant intra-individual variation was observed for both time periods involving Donor 2, these being Period 2 (nine samples, P = 0.002) and Period 4 (seven samples, P < 0.001). The combined data from all time periods exhibited a significant intra-individual variation for Donor 1 (P < 0.001) and Donor 2 (P < 0.001). These findings led to the conclusion that too much reliance should not be placed on the result from a single sample when assessing individual radiosensitivity status.

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“…In all reported results, G2 assay able to detect the RS differences in healthy donor and breast cancer patients [135,[147][148][149][150][151][152] (Table 2). About BRCA1/2 carriers, Ernestos et al [153] and Baeyens et al [139] have reported that breast cancer patients with BRCA1 or BRCA2 mutations were not radiosensitive than healthy women carrying no mutation.…”

Section: G2/0 Chromosomal Assaymentioning

confidence: 99%

“…BC cases (515) Lymphocyte 1.5 Gy non-Hispanic White 2. Healthy controls (402) γ-rays BC cases > Healthy control Mexican American BC cases > Healthy control African Americans BC cases ↔ Healthy controls Poggioli et al 2010 [ 150 ] G0 & G2 chromosomal assay 1. BC cases (23) Lymphocyte G2 assay G0 assay & G2 assay 2.…”

Section: Radiosensitivity Assays In Breast Cancermentioning

confidence: 99%

Molecular contribution of BRCA1 and BRCA2 to genome instability in breast cancer patients: review of radiosensitivity assays

et al. 2020

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Background DNA repair pathways, cell cycle arrest checkpoints, and cell death induction are present in cells to process DNA damage and prevent genomic instability caused by various extrinsic and intrinsic ionizing factors. Mutations in the genes involved in these pathways enhances the ionizing radiation sensitivity, reduces the individual’s capacity to repair DNA damages, and subsequently increases susceptibility to tumorigenesis. Body BRCA1 and BRCA2 are two highly penetrant genes involved in the inherited breast cancer and contribute to different DNA damage pathways and cell cycle and apoptosis cascades. Mutations in these genes have been associated with hypersensitivity and genetic instability as well as manifesting severe radiotherapy complications in breast cancer patients. The genomic instability and DNA repair capacity of breast cancer patients with BRCA1/2 mutations have been analyzed in different studies using a variety of assays, including micronucleus assay, comet assay, chromosomal assay, colony-forming assay, γ -H2AX and 53BP1 biomarkers, and fluorescence in situ hybridization. The majority of studies confirmed the enhanced spontaneous & radiation-induced radiosensitivity of breast cancer patients compared to healthy controls. Using G2 micronucleus assay and G2 chromosomal assay, most studies have reported the lymphocyte of healthy carriers with BRCA1 mutation are hypersensitive to invitro ionizing radiation compared to non-carriers without a history of breast cancer. However, it seems this approach is not likely to be useful to distinguish the BRCA carriers from non-carrier with familial history of breast cancer. Conclusion In overall, breast cancer patients are more radiosensitive compared to healthy control; however, inconsistent results exist about the ability of current radiosensitive techniques in screening BRCA1/2 carriers or those susceptible to radiotherapy complications. Therefore, developing further radiosensitivity assay is still warranted to evaluate the DNA repair capacity of individuals with BRCA1/2 mutations and serve as a predictive factor for increased risk of cancer mainly in the relatives of breast cancer patients. Moreover, it can provide more evidence about who is susceptible to manifest severe complication after radiotherapy.

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G0 and G2 Chromosomal Assays in the Evaluation of Radiosensitivity in a Cohort of Italian Breast Cancer Patients

Cited by 8 publications

References 27 publications

Individual Radiosensitivity as a Risk Factor for the Radiation-Induced Acute Radiodermatitis

Individual Radiosensitivity as a Risk Factor for the Radiation-Induced Acute Radiodermatitis

Intra-individual variation in G2 chromosomal radiosensitivity

Molecular contribution of BRCA1 and BRCA2 to genome instability in breast cancer patients: review of radiosensitivity assays

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