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      Association between miR34b/c Polymorphism rs4938723 and Cancer Risk: A Meta-Analysis of 11 Studies including 6169 Cases and 6337 Controls

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          Abstract

          Background

          The functional polymorphism rs4938723 in the promoter region of pri-miR-34b/c is potentially associated with susceptibility to several cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer. Here we conducted a comprehensive meta-analysis to investigate the association between rs4938723 and cancer risk.

          Material/Methods

          Eligible studies extracted from the databases of PubMed, Web of Science, and Cochrane Library were evaluated. Statistical analysis was performed using Revman 5.2 and STATA 12.0 software.

          Results

          By characterizing the extracted data, a total of 11 studies reported in 10 publications including 6169 cases and 6337 controls were selected for further analysis. Our results revealed a significant association between the rs4938723 polymorphism and cancer risk in the codominant model (TC vs. TT: OR=1.10, 95% CI=1.02–1.19, P=0.009) but not in other genetic models. In the stratified analysis of different cancer types, a significant association was found in nasopharyngeal cancer, osteosarcoma, and renal cell cancer. Furthermore, stratified analysis of ethnicity indicated that a highly significant association was shown in the Asian population in a codominant model (TC vs. TT: OR=1.13, 95% CI=1.03–1.24, P=0.007) when compared with African-Americans and Caucasians.

          Conclusions

          Overall, the current study suggests that the miR-34b/c rs4938723 polymorphism may be associated with the risk of cancers, including nasopharyngeal cancer, osteosarcoma, and renal cell cancer, and to some extent this polymorphism is closely related to cancer susceptibility in Asians.

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          Most cited references25

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          Global cancer statistics

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            Cancer statistics, 2013.

            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. A total of 1,660,290 new cancer cases and 580,350 cancer deaths are projected to occur in the United States in 2013. During the most recent 5 years for which there are data (2005-2009), delay-adjusted cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.5% per year in women. Overall, cancer death rates have declined 20% from their peak in 1991 (215.1 per 100,000 population) to 2009 (173.1 per 100,000 population). Death rates continue to decline for all 4 major cancer sites (lung, colorectum, breast, and prostate). Over the past 10 years of data (2000-2009), the largest annual declines in death rates were for chronic myeloid leukemia (8.4%), cancers of the stomach (3.1%) and colorectum (3.0%), and non-Hodgkin lymphoma (3.0%). The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of approximately 1.18 million deaths from cancer, with 152,900 of these deaths averted in 2009 alone. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket and other underserved populations. Copyright © 2012 American Cancer Society, Inc.
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              Is Open Access

              MicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cells

              Background MicroRNAs (miRNAs) have been implicated in cancer initiation and progression via their ability to affect expression of genes and proteins that regulate cell proliferation and/or cell death. Transcription of the three miRNA miR-34 family members was recently found to be directly regulated by p53. Among the target proteins regulated by miR-34 are Notch pathway proteins and Bcl-2, suggesting the possibility of a role for miR-34 in the maintenance and survival of cancer stem cells. Methodology/Principal Findings We examined the roles of miR-34 in p53-mutant human pancreatic cancer cell lines MiaPaCa2 and BxPC3, and the potential link to pancreatic cancer stem cells. Restoration of miR-34 expression in the pancreatic cancer cells by either transfection of miR-34 mimics or infection with lentiviral miR-34-MIF downregulated Bcl-2 and Notch1/2. miR-34 restoration significantly inhibited clonogenic cell growth and invasion, induced apoptosis and G1 and G2/M arrest in cell cycle, and sensitized the cells to chemotherapy and radiation. We identified that CD44+/CD133+ MiaPaCa2 cells are enriched with tumorsphere-forming and tumor-initiating cells or cancer stem/progenitor cells with high levels of Notch/Bcl-2 and loss of miR-34. More significantly, miR-34 restoration led to an 87% reduction of the tumor-initiating cell population, accompanied by significant inhibition of tumorsphere growth in vitro and tumor formation in vivo. Conclusions/Significance Our results demonstrate that miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer cells. Our data support the view that miR-34 may be involved in pancreatic cancer stem cell self-renewal, potentially via the direct modulation of downstream targets Bcl-2 and Notch, implying that miR-34 may play an important role in pancreatic cancer stem cell self-renewal and/or cell fate determination. Restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic cancer with loss of p53–miR34, potentially via inhibiting pancreatic cancer stem cells.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2014
                19 October 2014
                : 20
                : 1977-1982
                Affiliations
                Department of General Surgery, Ruijin Hospital, affiliated with Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Surgery, Shanghai, China
                Author notes
                Corresponding Authors: Baiyong Shen, e-mail: profshenby@ 123456gmail.com , Xiaxing Deng, e-mail: dxx888888@ 123456gmail.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                [*]

                Xinjing Wang and Xiongxiong Lu contributed equally to this work

                Article
                892350
                10.12659/MSM.892350
                4213004
                25326793
                fb8776a8-0af8-4845-a12c-a2a5b63a7865
                © Med Sci Monit, 2014

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License

                History
                : 29 August 2014
                : 05 October 2014
                Categories
                Special Reports

                genes,neoplasm,meta-analysis,micrornas,polymorphism,genetic
                genes, neoplasm, meta-analysis, micrornas, polymorphism, genetic

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