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      Five zinc finger protein 350 single nucleotide polymorphisms and the risks of breast cancer: a meta-analysis

      research-article
      1 , 2
      Oncotarget
      Impact Journals LLC
      breast cancer, meta-analysis, SNP, ZNF350, DNA damage

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          Abstract

          Some studies have reported an association between the zinc-finger protein 350 (ZNF350), also known as zinc-finger and BRCA1-interacting protein with a Kruppel-associated box (KRAB) domain (ZBRK1), and risks of breast cancer, although the results remain controversial. A systematic search was conducted on PubMed, Web of Science, EMBASE, Ovid, Chinese National Knowledge Databases, and WanFang databases with relevant keywords. Four studies of five distinct populations involving 5824 breast cancer cases were used to conduct a meta-analysis that summarizes the current evidence of 5 genetic polymorphisms: Asp35Asp, Leu66Pro, Pro373Pro, Ser472Pro, and Ser501Arg in the ZNF350 gene. The T allele in Asp35Asp polymorphisms not significantly associated with increased risk of breast cancer (OR: 1.08; 95% CI: 0.96–1.21). The minor C allele of the Asp35Asp polymorphism is protective in the overdominant model (OR = 1.14; 95% CI: 1.02–1.28). The Pro allele in the Leu66Pro polymorphism is protective in all of the models examined (allelic, dominant, recessive, and overdominant). The Pro373Pro is not associated with breast cancer in all of the models tested. The Pro allele of the Ser472Pro polymorphism is protective using the dominant model (OR = 0.10; 95% CI: 0.04–0.23) but deleterious using the overdominant model (OR = 1.14; 95% CI: 1.02–1.28). The Ser501Arg polymorphism is deleterious only when using the recessive model (OR = 1.21; 95% CI: 1.02–1.44). In conclusion, this meta-analysis suggests that genetic polymorphisms in the ZNF350 variant can increase, decrease, or have no effect on the risks of breast cancer depending on the polymorphism and genetic model used. Further studies will be required to validate these findings.

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          Most cited references27

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          A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.

          A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods. Probable predisposing mutations have been detected in five of eight kindreds presumed to segregate BRCA1 susceptibility alleles. The mutations include an 11-base pair deletion, a 1-base pair insertion, a stop codon, a missense substitution, and an inferred regulatory mutation. The BRCA1 gene is expressed in numerous tissues, including breast and ovary, and encodes a predicted protein of 1863 amino acids. This protein contains a zinc finger domain in its amino-terminal region, but is otherwise unrelated to previously described proteins. Identification of BRCA1 should facilitate early diagnosis of breast and ovarian cancer susceptibility in some individuals as well as a better understanding of breast cancer biology.
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            Is Open Access

            BRCA1 Recruitment to Transcriptional Pause Sites Is Required for R-Loop-Driven DNA Damage Repair

            Summary The mechanisms contributing to transcription-associated genomic instability are both complex and incompletely understood. Although R-loops are normal transcriptional intermediates, they are also associated with genomic instability. Here, we show that BRCA1 is recruited to R-loops that form normally over a subset of transcription termination regions. There it mediates the recruitment of a specific, physiological binding partner, senataxin (SETX). Disruption of this complex led to R-loop-driven DNA damage at those loci as reflected by adjacent γ-H2AX accumulation and ssDNA breaks within the untranscribed strand of relevant R-loop structures. Genome-wide analysis revealed widespread BRCA1 binding enrichment at R-loop-rich termination regions (TRs) of actively transcribed genes. Strikingly, within some of these genes in BRCA1 null breast tumors, there are specific insertion/deletion mutations located close to R-loop-mediated BRCA1 binding sites within TRs. Thus, BRCA1/SETX complexes support a DNA repair mechanism that addresses R-loop-based DNA damage at transcriptional pause sites.
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              The global breast cancer burden: variations in epidemiology and survival.

              Breast cancer is the most common type of cancer and the most common cause of cancer-related mortality among women worldwide. However, the burden is not evenly distributed, and, according to the best available data, there are large variations in the incidence, mortality, and survival between different countries and regions and within specific regions. Many complex factors underlie these variations, including population structure (eg, age, race, and ethnicity), lifestyle, environment, socioeconomic status, risk factor prevalence, mammography use, disease stage at diagnosis, and access to high-quality care. We review recent breast cancer incidence and mortality statistics and explore why these vary so greatly across the world. Further research is needed to fully understand the reasons for variations in breast cancer outcomes. This will aid the development of tailored strategies to improve outcomes in general as well as the standard of care for underserved populations and reduce the burden of breast cancer worldwide.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                5 December 2017
                7 October 2017
                : 8
                : 63
                : 107273-107282
                Affiliations
                1 From the Bachelor of Health Sciences, McMaster University, Hamilton, Ontario, Canada
                2 Department of General Surgery, Nanjing Drum Tower Hospital, Nanjing, China
                Author notes
                Correspondence to: Jianfeng Sang, glyy8c@ 123456163.com
                Article
                21620
                10.18632/oncotarget.21620
                5739812
                0ef3fe12-b937-44df-9c8f-46363e10b6f3
                Copyright: © 2017 Zeng et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 June 2017
                : 4 August 2017
                Categories
                Meta-Analysis

                Oncology & Radiotherapy
                breast cancer,meta-analysis,snp,znf350,dna damage
                Oncology & Radiotherapy
                breast cancer, meta-analysis, snp, znf350, dna damage

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