Increased Radiosensitivity as an Indicator of Genes Conferring Breast Cancer Susceptibility

Varga, Dominic; Vogel, Walther; Bender, Ariane; Surowy, Harald; Maier, Christiane; Deissler, Helmut; Sauer, Georg

doi:10.1007/s00066-007-1774-2

Cited by 8 publications

(9 citation statements)

References 37 publications

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“…Several other groups have also reported the detection of cell-free EBV-DNA in the serum or plasma of NPC patients and healthy controls, with highly variable detection rates from 31% to 96% for NPC patients and from 0% to 14% for healthy controls [30,35,43]. There are several possibilities to account for these discrepancies, such as the number of PCR amplification cycles, the sensitivity of each PCR technique, the speci- [46] and EBV-DNA detection in peripheral whole blood using PCR with specific primers to amplify the targeted region of the EBNA-1 gene, suggesting the reported association between EBV and NPC could be higher, if different methods of EBV detection were used [12].…”

Section: Discussionmentioning

confidence: 99%

HLA Class II Alleles and the Presence of Circulating Epstein-Barr Virus DNA in Greek Patients with Nasopharyngeal Carcinoma

et al. 2008

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Section: Discussionmentioning

confidence: 99%

HLA Class II Alleles and the Presence of Circulating Epstein-Barr Virus DNA in Greek Patients with Nasopharyngeal Carcinoma

et al. 2008

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“…Nine studies compared the RS of breast cancer patients with control individuals ( Table 1). The majority of studies (77.8%) reported that radiation-induced frequency of micronucleus was significantly higher in breast cancer group in comparison to control [5,10,11,133,135,136,145]. In contrast, Djuzenova et al determined no significant difference between the level of MNi in breast cancer patients and healthy participants using G2 micronucleus test [12] and Francies et al reported breast cancer patients with luminal are more radiosensitive compared to healthy control, while no difference between those with triple-negative breast cancer and healthy control has been detected [132].…”

Section: Radiosensitivity Assays In Breast Cancermentioning

confidence: 99%

“…Studies have reported that BRCA1 −/− mouse embryonic fibroblasts (MEFs) and human breast cancer line, HCC1937 [7,8], are highly sensitive to ionizing radiation and retrovirally transfecting these cells with wild-type BRCA1 diminished the ionizing radiation sensitivity and improved the efficiency of DSBs repair [9]. Likewise, the clinical studies stated BRCA1/2 mutation carriers are more radiosensitive than healthy control [5,10,11] and manifest more severe radiotherapy complications [12,13] due to having defective DNA damage repair system.…”

Section: Introductionmentioning

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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“…In vitro CRS is therefore considered to be a hallmark for BC and a marker for low-penetrant gene mutations predisposing to BC (3,4,6,7,9). The most detrimental form of ionizing radiationinduced DNA damage is the double strand break (DSB) due to its ability to generate chromosomal aberrations when misrepaired or left unrepaired.…”

Section: Introductionmentioning

confidence: 99%

Combined effect of polymorphisms in Rad51 and Xrcc3 on breast cancer risk and chromosomal radiosensitivity

et al. 2011

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Abstract. Enhanced in vitro chromosomal radiosensitivity (CRS) has been proposed as a marker for low-penetrance gene mutations predisposing to breast cancer (BC). Since the double strand break (DSB) is the most detrimental form of DNA damage induced by ionizing radiation, it is possible that mutations in genes encoding proteins involved in DSB repair affect breast cancer risk. The purpose of the present study was to examine whether five single nucleotide polymorphisms (SNPs) in Rad51 and Xrcc3 (rs1801320, rs1801321, rs1799796, rs861539 and rs1799794) exhibited an association with breast cancer susceptibility in a Belgian population of BC patients with a known or putative genetic predisposition. We also ascertained whether a relationship exists between the occurrence of the 'variant' alleles of these variations and in vitro CRS. Blood samples were obtained from BC patients and from healthy female individuals. Variations in the 5' UTR of Rad51 and Xrcc3 were genotyped, and statistical analysis was performed. The results showed that low-penetrant variations in Rad51 and Xrcc3, two proteins belonging to the homologous recombination DSB repair pathway, may modify BC risk in patients already carrying a pathological mutation in the highly penetrant BC genes BRCA1 and BRCA2. Combined risk genotype analysis revealed that Rad51 SNPs enhance BC risk in BRCA2 patients, whereas Xrcc3 SNPs significantly enhance BC risk in carriers of BRCA1 mutations and in patients with hereditary BC. When four putative risk genotypes of Rad51 and Xrcc3 were combined, positive significant odds ratios were obtained in the entire patient population and in patients with a hereditary history of disease. Although obtained from a limited number of patients, our data are supportive of a polygenic model whereby combinations of weak variations are responsible for an enhanced BC risk by acting jointly with high-penetrant mutations in BRCA1 or BRCA2.

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Increased Radiosensitivity as an Indicator of Genes Conferring Breast Cancer Susceptibility

Cited by 8 publications

References 37 publications

HLA Class II Alleles and the Presence of Circulating Epstein-Barr Virus DNA in Greek Patients with Nasopharyngeal Carcinoma

HLA Class II Alleles and the Presence of Circulating Epstein-Barr Virus DNA in Greek Patients with Nasopharyngeal Carcinoma

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

Combined effect of polymorphisms in Rad51 and Xrcc3 on breast cancer risk and chromosomal radiosensitivity

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