AIM To perform a meta-analysis of observational studies on inflammatory markers levels and occurrence of colorectal adenoma.METHODS Pub Med and EMBASE databases were searched until March 2016 for the articles reportin...AIM To perform a meta-analysis of observational studies on inflammatory markers levels and occurrence of colorectal adenoma.METHODS Pub Med and EMBASE databases were searched until March 2016 for the articles reporting on the circulating levels of inflammatory markers, including: C-reactive protein(CRP), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-a) and risk of colorectal adenoma. Random-effects models were used to calculate summary odds ratios(ORs) with 95%CIs for the highest vs lowest category of exposure. Heterogeneity was assessed by using the Q test and I2 statistic. Subgroup analyses were also performed to test for potential source of heterogeneity.RESULTS A total of 14 case-control studies were included. Ten studies on CRP including a total of 3350 cases and 4168 controls showed non-significant summary(OR = 1.23, 95%CI: 0.98-1.54; I2 = 54%, P heterogeneity = 0.01) in the general analysis, but significant increased odds when considering only advanced adenoma(OR = 1.59, 95%CI: 1.09-2.32; I2 = 44%, P heterogeneity = 0.15). Subgroup and stratified analyses revealed a potential influence of smoking status and aspirin use on the association between CRP levels and colorectal adenoma. Five studies examined the association between circulating levels of TNF-a and colorectal adenoma risk, including a total of 1,568 cases and 2,832 controls. The summary OR for the highest vs the lowest category of exposure was 1.00(95%CI: 0.77-1.29). The relationship between circulating IL-6 levels and colorectal adenoma risk was investigated in 7 studies including a total of 1936 cases and 3611 controls. The summary OR for the highest vs the lowest category of exposure was 1.19(95%CI: 0.92-1.55).CONCLUSION Summary of current evidence suggests a positive association of CRP levels and advanced colorectal adenoma risk. The role of potential confounding factors should be further evaluated.展开更多
Regulation of the Hippo signaling pathway is essential for normal organ growth and tissue homeostasis.The proteins that act to regulate this pathway are important for ensuring proper function and cellular location.Deu...Regulation of the Hippo signaling pathway is essential for normal organ growth and tissue homeostasis.The proteins that act to regulate this pathway are important for ensuring proper function and cellular location.Deubiquitinases(DUBs)are a family of proteases that act upon many proteins.While ubiquitinases add ubiquitin and target proteins for degradation,DUBs act by removing ubiquitin(Ub)moieties.Changes in ubiquitin chain topology results in the stabilization of proteins,membrane trafficking,and the alteration of cellular localization.While the roles of these proteins have been well established in a cancer setting,their convergence in cancer is still under investigation.In this review,we discuss the roles that DUBs play in the regulation of the Hippo signaling pathway for homeostasis and disease.展开更多
Background:DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer(PCa).However,it has not yet been possible to incorporate information of DNA me...Background:DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer(PCa).However,it has not yet been possible to incorporate information of DNA methylation and gene expression into polygenic risk scores(PRSs).Here,we aimed to develop and validate an improved PRS for PCa risk by incorporating genetically predicted gene expression and DNA methylation,and other genomic information using an integrative method.Methods:Using data from the PRACTICAL consortium,we derived multiple sets of genetic scores,including those based on available single-nucleotide polymorphisms through widely used methods of pruning and thresholding,LDpred,LDpred-funt,AnnoPred,and EBPRS,as well as PRS constructed using the genetically predicted gene expression and DNA methylation through a revised pruning and thresholding strategy.In the tuning step,using the UK Biobank data(1458 prevalent cases and 1467 controls),we selected PRSs with the best performance.Using an independent set of data from the UK Biobank,we developed an integrative PRS combining information from individual scores.Furthermore,in the testing step,we tested the performance of the integrative PRS in another independent set of UK Biobank data of incident cases and controls.Results:Our constructed PRS had improved performance(C statistics:76.1%)over PRSs constructed by individual benchmark methods(from 69.6%to 74.7%).Furthermore,our new PRS had much higher risk assessment power than family history.The overall net reclassification improvement was 69.0%by adding PRS to the baseline model compared with 12.5%by adding family history.Conclusions:We developed and validated a new PRS which may improve the utility in predicting the risk of developing PCa.Our innovative method can also be applied to other human diseases to improve risk prediction across multiple outcomes.展开更多
文摘AIM To perform a meta-analysis of observational studies on inflammatory markers levels and occurrence of colorectal adenoma.METHODS Pub Med and EMBASE databases were searched until March 2016 for the articles reporting on the circulating levels of inflammatory markers, including: C-reactive protein(CRP), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-a) and risk of colorectal adenoma. Random-effects models were used to calculate summary odds ratios(ORs) with 95%CIs for the highest vs lowest category of exposure. Heterogeneity was assessed by using the Q test and I2 statistic. Subgroup analyses were also performed to test for potential source of heterogeneity.RESULTS A total of 14 case-control studies were included. Ten studies on CRP including a total of 3350 cases and 4168 controls showed non-significant summary(OR = 1.23, 95%CI: 0.98-1.54; I2 = 54%, P heterogeneity = 0.01) in the general analysis, but significant increased odds when considering only advanced adenoma(OR = 1.59, 95%CI: 1.09-2.32; I2 = 44%, P heterogeneity = 0.15). Subgroup and stratified analyses revealed a potential influence of smoking status and aspirin use on the association between CRP levels and colorectal adenoma. Five studies examined the association between circulating levels of TNF-a and colorectal adenoma risk, including a total of 1,568 cases and 2,832 controls. The summary OR for the highest vs the lowest category of exposure was 1.00(95%CI: 0.77-1.29). The relationship between circulating IL-6 levels and colorectal adenoma risk was investigated in 7 studies including a total of 1936 cases and 3611 controls. The summary OR for the highest vs the lowest category of exposure was 1.19(95%CI: 0.92-1.55).CONCLUSION Summary of current evidence suggests a positive association of CRP levels and advanced colorectal adenoma risk. The role of potential confounding factors should be further evaluated.
基金This work was supported by the Roswell Park Cancer Institute and National Cancer Institute(NCI)Grant#P30 CA016056,Roswell Park Alliance Foundation,the National Cancer Institute(NCI)R01 CA207504 and the American Cancer Society Research Scholar Grant RSG-14-214-01-TBE(to J.Z.).
文摘Regulation of the Hippo signaling pathway is essential for normal organ growth and tissue homeostasis.The proteins that act to regulate this pathway are important for ensuring proper function and cellular location.Deubiquitinases(DUBs)are a family of proteases that act upon many proteins.While ubiquitinases add ubiquitin and target proteins for degradation,DUBs act by removing ubiquitin(Ub)moieties.Changes in ubiquitin chain topology results in the stabilization of proteins,membrane trafficking,and the alteration of cellular localization.While the roles of these proteins have been well established in a cancer setting,their convergence in cancer is still under investigation.In this review,we discuss the roles that DUBs play in the regulation of the Hippo signaling pathway for homeostasis and disease.
基金NIH,Grant/Award Number:R03 AG070669Canadian Institutes of Health Research,European Commission’s Seventh Framework Programme grant agreement,Grant/Award Number:HEALTH-F2-2009-223175+11 种基金Cancer Research UK,Grant/Award Numbers:C5047/A7357,C1287/A10118,C1287/A16563,C5047/A3354,C5047/A10692,C16913/A6135The National Institute of Health(NIH)Cancer Post-Cancer GWAS,Grant/Award Number:1 U19 CA 148537-01The National Health and Medical Research Council,Australia,Grant/Award Numbers:126402,209057,251533,396414,450104,504700,504702,504715,623204,940394,614296US National Institutes of Health(NIH),Grant/Award Number:U19 CA 148537Prostate cancer SuscEptibility(ELLIPSE),Grant/Award Number:X01HG007492Center for Inherited Disease Research(CIDR),Grant/Award Number:HHSN268201200008INIH NCI,Grant/Award Number:U01 CA188392European Community’s Seventh Framework Programme,Grant/Award Number:223175Post-Cancer GWAS initiative,Grant/Award Numbers:1U19 CA148537,1U19 CA148065,1U19 CA148112U.S.National Institutes of Health,National Cancer Institute,Grant/Award Numbers:U01-CA98233,U01-CA98710,U01-CA98216,U01-CA98758Swedish Cancer Foundation,Grant/Award Numbers:09-0677,11-484,12-823Swedish Research Council,Swedish Research Council,Grant/Award Numbers:K2010-70X-20430-04-3,2014-2269。
文摘Background:DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer(PCa).However,it has not yet been possible to incorporate information of DNA methylation and gene expression into polygenic risk scores(PRSs).Here,we aimed to develop and validate an improved PRS for PCa risk by incorporating genetically predicted gene expression and DNA methylation,and other genomic information using an integrative method.Methods:Using data from the PRACTICAL consortium,we derived multiple sets of genetic scores,including those based on available single-nucleotide polymorphisms through widely used methods of pruning and thresholding,LDpred,LDpred-funt,AnnoPred,and EBPRS,as well as PRS constructed using the genetically predicted gene expression and DNA methylation through a revised pruning and thresholding strategy.In the tuning step,using the UK Biobank data(1458 prevalent cases and 1467 controls),we selected PRSs with the best performance.Using an independent set of data from the UK Biobank,we developed an integrative PRS combining information from individual scores.Furthermore,in the testing step,we tested the performance of the integrative PRS in another independent set of UK Biobank data of incident cases and controls.Results:Our constructed PRS had improved performance(C statistics:76.1%)over PRSs constructed by individual benchmark methods(from 69.6%to 74.7%).Furthermore,our new PRS had much higher risk assessment power than family history.The overall net reclassification improvement was 69.0%by adding PRS to the baseline model compared with 12.5%by adding family history.Conclusions:We developed and validated a new PRS which may improve the utility in predicting the risk of developing PCa.Our innovative method can also be applied to other human diseases to improve risk prediction across multiple outcomes.
