Rad51 paralogs and the risk of unselected breast cancer: A case-control study

Grešner, Peter; Jabłońska, Ewa; Gromadzińska, Jolanta

doi:10.1371/journal.pone.0226976

Cited by 7 publications

(5 citation statements)

References 64 publications

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“…Studies have shown multiple altered variants in DNA repair genes implied in BC predisposition, development, and outcome [ 11 , 12 , 13 , 14 ], including BRCA and non-BRCA genes. Among these, pathogenic variants in the high penetrance BRCA1/2 genes account for 50–60% and the remaining variants, to non-BRCA genes of moderate and low penetrance, including ATM , PALB2 , RAD51 , and BARD1 , all involved in double-strand break repair pathways [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. For this reason, it is relevant to elucidate the mechanisms of DNA repair genes in BC, using different approaches such as in silico, in vitro, and in vivo models.…”

Section: Introductionmentioning

confidence: 99%

DNA Repair Genes as Drug Candidates for Early Breast Cancer Onset in Latin America: A Systematic Review

Urbina-Jara

Martinez-Ledesma

Rojas-Martínez

et al. 2021

IJMS

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The prevalence of breast cancer in young women (YWBC) has increased alarmingly. Significant efforts are being made to elucidate the biological mechanisms concerning the development, prognosis, and pathological response in early-onset breast cancer (BC) patients. Dysfunctional DNA repair proteins are implied in BC predisposition, progression, and therapy response, underscoring the need for further analyses on DNA repair genes. Public databases of large patient datasets such as METABRIC, TCGA, COSMIC, and cancer cell lines allow the identification of variants in DNA repair genes and possible precision drug candidates. This study aimed at identifying variants and drug candidates that may benefit Latin American (LA) YWBC. We analyzed pathogenic variants in 90 genes involved in DNA repair in public BC datasets from METABRIC, TCGA, COSMIC, CCLE, and COSMIC Cell Lines Project. Results showed that reported DNA repair germline variants in the LA dataset are underrepresented in large databases, in contrast to other populations. Additionally, only six gene repair variants in women under 50 years old from the study population were reported in BC cell lines. Therefore, there is a need for new approaches to study DNA repair variants reported in young women from LA.

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Section: Introductionmentioning

confidence: 99%

DNA Repair Genes as Drug Candidates for Early Breast Cancer Onset in Latin America: A Systematic Review

Urbina-Jara

Martinez-Ledesma

Rojas-Martínez

et al. 2021

IJMS

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“…XRCC3 rs861539 (p.Thr241Met) is a non-synonymous SNP in the ATP-binding domain of the protein that affects XRCC3 interactions with other proteins [ 43 ]. Several studies investigated the role of this SNP in response to RT in different cancer types.…”

Section: Discussionmentioning

confidence: 99%

NBN, RAD51 and XRCC3 Polymorphisms as Potential Predictive Biomarkers of Adjuvant Radiotherapy Toxicity in Early HER2-Positive Breast Cancer

Goričar

Dugar

Dolžan

et al. 2022

Cancers

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Radiotherapy (RT) for breast cancer significantly impacts patient survival and causes adverse events. Double-strand breaks are the most harmful type of DNA damage associated with RT, which is repaired through homologous recombination (HRR). As genetic variability of DNA repair genes could affect response to RT, we aimed to evaluate the association of polymorphisms in HRR genes with tumor characteristics and the occurrence of RT adverse events in early HER2-positive breast cancer. Our study included 101 breast cancer patients treated with adjuvant RT and trastuzumab. All patients were genotyped for eight single nucleotide polymorphisms in NBN, RAD51 and XRCC3 using competitive allele-specific PCR. Carriers of XRCC3 rs1799794 GG genotype were less likely to have higher tumor differentiation grade (OR = 0.05, 95% CI = 0.01–0.44, p = 0.007). Carriers of RAD51 rs1801321 TT genotype were more likely to have higher NYHA class in univariable (OR = 10.0; 95% CI = 1.63–61.33; p = 0.013) and multivariable (OR = 9.27; 95% CI = 1.28–67.02; p = 0.027) analysis. Carriers of RAD51 rs12593359 GG genotype were less likely to have higher NYHA class in univariable (OR = 0.09; 95% CI = 0.01–0.79; p = 0.030) and multivariable (OR = 0.07; 95% CI = 0.01–0.81; p = 0.034) analysis. Carriers of XRCC3 rs1799794 GG genotypes experienced more skin adverse events based on LENT-SOMA scale in univariable (OR = 5.83; 95% CI = 1.22–28.00; p = 0.028) and multivariable (OR = 10.90; 95% CI = 1.61–73.72; p = 0.014) analysis. In conclusion, XRCC3 and RAD51 polymorphisms might contribute to RT adverse events in early HER2-positive breast cancer patients.

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“…19 studies including 13 countries) [44], Polish [40], and European [22] women. We also observed that the mutant CC genotype elevated the risk of metastasis in individuals with the homozygous mutant genotype.…”

Section: Plos Onementioning

confidence: 99%

“…Last decade, there have been conflicting reports regarding the impact of the HRR gene polymorphisms on BC risk [20][21][22][23][24][25][26]. Besides, there is a paucity of information regarding the impact of HRR gene polymorphisms on South Indian women's BC etiology.…”

Section: Introductionmentioning

confidence: 99%

Homologous recombination DNA repair gene RAD51, XRCC2 & XRCC3 polymorphisms and breast cancer risk in South Indian women

et al. 2022

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Background Homologous recombination repair (HRR) accurately repairs the DNA double-strand breaks (DSBs) and is crucial for genome stability. Genetic polymorphisms in crucial HRR pathway genes might affect genome stability and promote tumorigenesis. Up to our knowledge, the present study is the first to investigate the impact of HRR gene polymorphisms on BC development in South Indian women. The present population-based case-control study investigated the association of polymorphisms in three key HRR genes (XRCC2-Arg188His, XRCC3-Thr241Met and RAD51-G135C) with BC risk. Materials and methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping the HRR variants in 491 BC cases and 493 healthy women. Results We observed that the XRCC3 Met allele was significantly associated with BC risk [OR:1.27 (95% CI: 1.02–1.60); p = 0.035]. In addition, the homozygous mutant (C/C) genotype of RAD51 G135C variant conferred 2.19 fold elevated risk of BC [OR: 2.19 (95% CI: 1.06–4.54); p = 0.034]. Stratified analysis of HRR variants and BC clinicopathological features revealed that the XRCC3-Thr241Met and RAD51-G135C variants are associated with BC progression. Combined SNP analysis revealed that the individuals with RAD51-C/C, XRCC2-Arg/Arg, and XRCC3-Thr/Thr genotype combination have three-fold increased BC risk. Conclusion The present study imparts additional evidence that genetic variants in crucial HRR pathway genes might play a pivotal role in modulating BC risk in South Indian women.

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Rad51 paralogs and the risk of unselected breast cancer: A case-control study

Cited by 7 publications

References 64 publications

DNA Repair Genes as Drug Candidates for Early Breast Cancer Onset in Latin America: A Systematic Review

DNA Repair Genes as Drug Candidates for Early Breast Cancer Onset in Latin America: A Systematic Review

NBN, RAD51 and XRCC3 Polymorphisms as Potential Predictive Biomarkers of Adjuvant Radiotherapy Toxicity in Early HER2-Positive Breast Cancer

Homologous recombination DNA repair gene RAD51, XRCC2 & XRCC3 polymorphisms and breast cancer risk in South Indian women

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