Blog
About

8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin’s chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05). Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction ( P = 0.001). Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only ( P = 0.01 and P = 0.004, respectively), however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk ( P interaction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68–0.86; rs1105879 OR = 0.77 95% CI = 0.69–0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only ( P interaction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk ( P interaction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer risk.

          Related collections

          Most cited references 44

          • Record: found
          • Abstract: not found
          • Article: not found

          Measuring inconsistency in meta-analyses.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Meta-analysis in clinical trials.

            This paper examines eight published reviews each reporting results from several related trials. Each review pools the results from the relevant trials in order to evaluate the efficacy of a certain treatment for a specified medical condition. These reviews lack consistent assessment of homogeneity of treatment effect before pooling. We discuss a random effects approach to combining evidence from a series of experiments comparing two treatments. This approach incorporates the heterogeneity of effects in the analysis of the overall treatment efficacy. The model can be extended to include relevant covariates which would reduce the heterogeneity and allow for more specific therapeutic recommendations. We suggest a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Proteomics. Tissue-based map of the human proteome.

              Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body. Copyright © 2015, American Association for the Advancement of Science.
                Bookmark

                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Project administrationRole: Supervision
                Role: Formal analysisRole: SupervisionRole: Writing – review & editing
                Role: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Supervision
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: Project administrationRole: Writing – review & editing
                Role: Data curationRole: Funding acquisition
                Role: Data curationRole: Funding acquisition
                Role: Data curationRole: Funding acquisition
                Role: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisition
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: Resources
                Role: ConceptualizationRole: Data curationRole: Funding acquisition
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisition
                Role: ConceptualizationRole: Data curationRole: Funding acquisition
                Role: ConceptualizationRole: Data curationRole: Funding acquisition
                Role: ConceptualizationRole: Data curationRole: Funding acquisition
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                9 February 2018
                2018
                : 13
                : 2
                Affiliations
                [1 ] Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom
                [2 ] Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom
                [3 ] Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States of America
                [4 ] Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
                [5 ] School of Medicine, University of Dundee, Dundee, United Kingdom
                [6 ] Stanford Cancer Institute, Stanford, California, United States of America
                [7 ] Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America
                [8 ] Melbourne School of Population and Global Health, The University of Melbourne, Carlton, Australia
                [9 ] University of Hawaii, Manoa, Hawaii, United States of America
                [10 ] Mayo Clinic, Scottsdale, Arizona, United States of America
                [11 ] Mayo Clinic, Rochester, Minnesota, United States of America
                [12 ] Centre for Public Health Research, Massey University, Wellington, New Zealand
                National Institute of Environmental Health Sciences, UNITED STATES
                Author notes

                Competing Interests: John Burn and Cornelia M. Ulrich are consultant/advisory board member of Bayer Pharma who manufacture aspirin. Other authors have declared that no competing interest exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Article
                PONE-D-17-10794
                10.1371/journal.pone.0192223
                5806861
                29425227
                © 2018 Sheth et al

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

                Page count
                Figures: 2, Tables: 1, Pages: 17
                Product
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000054, National Cancer Institute;
                Award ID: U01 CA122839 and R01 CA143237
                Award Recipient :
                Funded by: National Cancer Institute
                Award ID: U01/U24 CA074783 and U01/U24 CA074794
                Funded by: funder-id http://dx.doi.org/10.13039/501100000289, Cancer Research UK;
                Award ID: C588/A19167
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000054, National Cancer Institute;
                Award ID: UM1 CA167551-NIH-CCFR
                Funded by: funder-id http://dx.doi.org/10.13039/100000054, National Cancer Institute;
                Award ID: U01 CA074778 and U01/U24 CA097735
                The UK-CCSG study was supported by the Cancer Research UK grant C588/A19167. The NIH-CCFR study was supported by grant UM1 CA167551 from the National Cancer Institute and through cooperative agreements with the following CCFR centers: Australasian Colorectal Cancer Family Registry (U01 CA074778 and U01/U24 CA097735), Ontario Familial Colorectal Cancer Registry (U01/U24 CA074783) and Seattle Colorectal Cancer Family Registry (U01/U24 CA074794). The Colon CFR Illumina GWAS was supported by funding from the National Cancer Institute, National Institutes of Health (U01 CA122839 and R01 CA143237 to Graham Casey). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Colon Cancer Family Registry (CCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CCFR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Colorectal Cancer
                Biology and Life Sciences
                Genetics
                Genetic Loci
                Alleles
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Medicine and health sciences
                Pharmacology
                Drugs
                Analgesics
                NSAIDs
                Medicine and health sciences
                Pain management
                Analgesics
                NSAIDs
                Biology and Life Sciences
                Genetics
                Molecular Genetics
                Biology and Life Sciences
                Molecular Biology
                Molecular Genetics
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Adenomas
                Biology and Life Sciences
                Genetics
                Heredity
                Genetic Mapping
                Variant Genotypes
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Gastrointestinal Tumors
                Rectal Cancer
                Custom metadata
                Anonymized UK-CCSG data are available in the Supporting Information files. The original UK-CCSG data are available at request from D. Timothy Bishop (email: D.T.Bishop@ 123456leeds.ac.uk ). The NIH-CCFR data are available at request from Allyson Templeton (email: atemplet@ 123456fredhutch.org ). Others would be able to access these data in the same manner as the authors and the authors did not have any special access privileges that others would not have.

                Uncategorized

                Comments

                Comment on this article