Association between the<i>BRCA2</i>rs144848 polymorphism and cancer susceptibility: a meta-analysis

Li, Qiuyan; Guan, Rongwei; Qiao, Yuandong; Liu, Chang; He, Ning; Zhang, Xuelong; Jia, Xueyuan; Sun, Haiming; Yu, Jingcui; Xu, Lei

doi:10.18632/oncotarget.16242

Cited by 21 publications

(15 citation statements)

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“…3,6,25,26 The BRCA2 gene has an important role in the repair of double-strand DNA breaks, functioning by regulating the intracellular transport and the activity of RAD51, a critical protein in homologous recombination. [27][28][29] The most frequent variants found for this gene, such as rs169547, rs206075, rs206076, and rs9534262, are similar to those found in other studies. 30,31 These have been considered benign mutations [32][33][34] -the first three were reported in…”

Section: Discussionsupporting

confidence: 86%

Frequency of Variants in DNA-Repair Genes in a Southwest Colombian Population

2019

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Objective To describe the frequency of mutations in DNA-repair genes in a southwestern Colombian population. Methods We have designed an observational study, including 162 people from all ages from southwest Colombia. We have extracted and collected their DNA in filters. We have immersed the DNA in a phosphate buffer along with DNeasy package (Thermo Fisher Scientific, Waltham, MA, USA). The preparation process was with the TruSeq Exome Library Prep (Illumina, Inc. San Diego, CA, USA), then the obtained libraries were normalized with TruSeq Rapid Exome (Illumina, Inc. San Diego, CA, USA). We sequenced the full exome and identified the variants associated with 12 genes (ataxia telangiectasia mutated [ATM], BRCA1 DNA repair associated [BRCA1], BRCA2 DNA repair associated [BRCA2], checkpoint kinase 2 [CHEK2], epithelial cell adhesion molecule [EPCAM], homeobox protein Hox-B13 [HOXB13], mutS homolog 1, 2 and 6 [MLH1, MSH2, MSH6], nibrin [NBN], PMS1 homolog 2, mismatch repair system component [PMS2], and tumor protein p53 [TP53]). Descriptive statistics were performed with the R software (The R Foundation for Statistical Computing, Vienna, Austria). Results A total of 7,315,466 pieces of data were sequenced in this population. The most frequently mutated genes were ATM (1,221 pieces of data; 13.2%), BRCA1 (1,178 pieces of data; 12.8%), BRCA2 (1,484 pieces of data; 16.12%), and NBN (965 pieces of data; 10.42%). The most common single nucleotide polymorphisms (SNPs) in these 12 genes were the following: BRCA2 (rs169547, rs206075, rs206076); ATM (rs659243, rs228589); TP53 (rs1625895, rs1042522, rs1642785); PMS2 (rs2228006, rs1805319); NBN (rs709816); and MSH6 (rs3136367) Conclusion The BRCA2, ATM, BRCA1 and NBN DNA-repair genes were the most frequently mutated in this southwestern Colombian Population.

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Section: Discussionsupporting

confidence: 86%

Frequency of Variants in DNA-Repair Genes in a Southwest Colombian Population

2019

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“…Cells exhibited the TP53 mutation 796G > T (G266Ter). In addition, cells carried the 1114A > C (N372H) substitution in the BRCA2 gene, which has been associated with increased cancer risk ( Li et al., 2017 ). Both mutations were also found in the original tumor, which had been diagnosed as an HGSOC by a trained pathologist (G.B.).…”

Section: Methodsmentioning

confidence: 99%

CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells

et al. 2018

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SummaryCancer-initiating cells (CICs) have been implicated in tumor development and aggressiveness. In ovarian carcinoma (OC), CICs drive tumor formation, dissemination, and recurrence, as well as drug resistance, thus accounting for the high death-to-incidence ratio of this neoplasm. However, the molecular mechanisms that underlie such a pathogenic role of ovarian CICs (OCICs) remain elusive. Here, we have capitalized on primary cells either from OC or from its tissues of origin to obtain the transcriptomic profile associated with OCICs. Among the genes differentially expressed in OCICs, we focused on CD73, which encodes the membrane-associated 5′-ectonucleotidase. The genetic inactivation of CD73 in OC cells revealed that this molecule is causally involved in sphere formation and tumor initiation, thus emerging as a driver of OCIC function. Furthermore, functional inhibition of CD73 via either a chemical compound or a neutralizing antibody reduced sphere formation and tumorigenesis, highlighting the druggability of CD73 in the context of OCIC-directed therapies. The biological function of CD73 in OCICs required its enzymatic activity and involved adenosine signaling. Mechanistically, CD73 promotes the expression of stemness and epithelial-mesenchymal transition-associated genes, implying a regulation of OCIC function at the transcriptional level. CD73, therefore, is involved in OCIC biology and may represent a therapeutic target for innovative treatments aimed at OC eradication.

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“…These two variants are present in our patient suggesting that they could be in linkage disequilibrium. A recent metanalysis study reveals that the rs144848 H allele could be a low-penetrant risk factor enhancing carcinogenesis in breast cancer 60 . The K3326X, which co-segregates in some cases with other deleterious BRCA2 mutations, is described as a low penetrant variant associated with a modestly high risk of breast cancer 59,61 .…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing reveals a combination of rare high and low penetrance variants that correlates with familial breast cancer relative risk

Rekaya

Hamdi

Benna

et al. 2020

Preprint

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Background: Genetic risk factors of breast cancer are very heterogeneous and complex. They vary according to the familial relative risk, the age of cancer diagnosis of the index case and the age of the affected relatives.Objectives: We aimed to investigate and identify simultaneously all rare pathogenic and common variants in unrelated BC cases with different relative risk ratios for breast cancer and evaluate the contribution of these variants in genetic susceptibility to breast cancer.Patients and Methods: All frequent mutations in BRCA genes previously identified in Tunisia have been excluded by Sanger sequencing in 42 women affected with high family risk having at least 3 cancer affected related individuals. Two unrelated cases having two different family histories (in terms of different numbers of affected first-degree relatives and young age onset) have been selected for whole exome sequencing. The first family is composed of three sisters F1.1, F1.2 and F1.3 affected at 46, 50, and 32 years old, respectively. The second has only two breast cancer cases, F2.2 and F2.4, affected at late age 61 and 70 years old, respectively, in addition to other 5 members affected by different kinds of cancer. Selected high risk variants were confirmed and segregation analysis was performed using Sanger sequencing. Results and discussion: For F1.1 case, we identified a pathogenic frame-shift loss of function variant in BRCA2 p.Val1283Lysfs. For F2.2 we identified a pathogenic rare variant in OGG1, p.Arg46Gln that co-segregates with a rare non sense variant in BRCA2 p.K3326X, only in the breast cancer affected cases. Moreover, F2.2 patient has 9 other common low penetrant variants in different loci known to represent independently minor, but cumulatively significant, increased risk for breast cancer.Conclusion: Family history and the young age at onset for patient F1.1 correlate with the presence of a rare high penetrant variant (p.Val1283Lysfs) in BRCA2 gene. However, the late age at onset and the less severe phenotype for patient F2.2 are probably the consequence of the presence of a pathogenic variant p.Arg46Gln in OGG1 gene that co-segregate with a low penetrant variant Lys3326X in BRCA2 only in breast cancer cases.

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Association between theBRCA2rs144848 polymorphism and cancer susceptibility: a meta-analysis

Cited by 21 publications

References 50 publications

Frequency of Variants in DNA-Repair Genes in a Southwest Colombian Population

Frequency of Variants in DNA-Repair Genes in a Southwest Colombian Population

CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells

Whole exome sequencing reveals a combination of rare high and low penetrance variants that correlates with familial breast cancer relative risk

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