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      CASP8 -652 6N insertion/deletion polymorphism and overall cancer risk: evidence from 49 studies

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          Abstract

          The CASP8 -652 6N insertion/deletion (I/D) polymorphism reduces expression of caspase 8. We conducted a meta-analysis to clarify the relationship between this polymorphism and cancer risk. Eligible articles were retrieved from PubMed, EMBASE, CNKI, and WANFANG databases through February 2017. A total of 33 articles with 49 studies, including 33,494 cases and 36,397 controls, were analyzed. We found that the CASP8 -652 6N ins/del polymorphism was associated with decreased overall cancer risk in five genetic models [DD vs. II: odds ratio (OR)=0.76, 95% confidence interval (CI)=0.69–0.84, ID vs. II: OR=0.87, 95% CI=0.83–0.92, DD vs. ID/II: OR=0.82, 95% CI=0.75–0.89, ID/DD vs. II: OR=0.85, 95% CI=0.80–0.90, and D vs. I: OR=0.87, 95% CI=0.83–0.91]. Stratified analyses showed that the polymorphism was associated with decreased risk of colorectal, breast, esophageal, renal cell, lung, cervical, bladder, gastric, and other cancers. Overall cancer risk was reduced in Asian and Caucasian patients, both hospital- and population-based studies, and both high and low quality studies. Our results highlight the role of the CASP8 -652 6N ins/del polymorphism in decreasing cancer risk. Further studies with large-cohort populations, especially for specific cancer types and ethnic groups, are needed to confirm our findings.

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          Cell death: critical control points.

          Programmed cell death is a distinct genetic and biochemical pathway essential to metazoans. An intact death pathway is required for successful embryonic development and the maintenance of normal tissue homeostasis. Apoptosis has proven to be tightly interwoven with other essential cell pathways. The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics.
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            Association studies for finding cancer-susceptibility genetic variants.

            Cancer is the result of complex interactions between inherited and environmental factors. Known genes account for a small proportion of the heritability of cancer, and it is likely that many genes with modest effects are yet to be found. Genetic-association studies have been widely used in the search for such genes, but success has been limited so far. Increased knowledge of the function of genes and the architecture of human genetic variation combined with new genotyping technologies herald a new era of gene mapping by association.
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              Association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma susceptibility: Evidence from a meta-analysis

              Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism and DNA synthesis. A number of studies have examined the association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma (NHL) susceptibility; however, the conclusions were contradictory. We searched available publications assessing the polymorphisms of MTHFR and NHL susceptibility from MEDLINE, EMBASE and CBM. Genotype-based mRNA expression analysis was performed using data from 270 individuals with three different ethnicities. Ultimately, a total of 7448 cases and 11146 controls from 25 studies were included for the C677T polymorphism, 6173 cases and 9725 controls from 19 studies for the A1298C polymorphism. Pooled results indicated that neither C677T nor A1298C polymorphism was associated with NHL susceptibility. However, C677T polymorphism showed a statistically significantly increased risk for Caucasians, but a decreased risk for Asians in the subgroup analysis by ethnicity. The same variants may confer increased susceptibility to develop follicular lymphoma (FL). Moreover, A1298C polymorphism was associated with increased NHL risk for Asians. This meta-analysis indicated that C677T polymorphism was associated with altered NHL susceptibility for Caucasians, Asians and FL. Increased NHL risk was also shown for A1298C among Asians. These findings warrant validation in large and well-designed prospective studies.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                22 August 2017
                25 May 2017
                : 8
                : 34
                : 56780-56790
                Affiliations
                1 Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
                2 Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
                3 Department of Otolaryngology, The First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-Sen University), Foshan 528000, China
                4 Department of Joint Surgery and Orthopaedic Trauma, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
                5 The Second People's Hospital of FuTian District, Shenzhen 518000, China
                6 School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China
                7 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
                8 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
                Author notes
                Correspondence to: Juan Cheng, mdchengjuan@ 123456sohu.com
                Article
                18187
                10.18632/oncotarget.18187
                5593601
                0dd82d96-ca34-443c-b481-34da5655953b
                Copyright: © 2017 Cai et al.

                This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 13 March 2017
                : 24 April 2017
                Categories
                Research Paper

                Oncology & Radiotherapy
                casp8,-652 6n insertion/deletion,polymorphism,cancer risk,meta-analysis
                Oncology & Radiotherapy
                casp8, -652 6n insertion/deletion, polymorphism, cancer risk, meta-analysis

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