Genetic Polymorphisms in Genes Relevant to One-carbon Metabolism and Colon Cancer Risk PDF Download

Author: Amy Yu-Ling Liu
Publisher:
ISBN:
Category :
Languages : en
Pages : 176

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Author: Sang-Woon Choi
Publisher: CRC Press
ISBN: 1000611337
Category : Medical
Languages : en
Pages : 325

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The complete mapping of the human genome, along with the development of sophisticated molecular technologies, has accelerated research on the relationship between nutrients and genes. This has led to compelling evidence garnered from epidemiological and experimental observations supporting the idea that the interaction between nutrients and genes i

Author: Paolo Vineis
Publisher:
ISBN:
Category : Medical
Languages : en
Pages : 530

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The study of interactions between genes and environmental exposures ha s expanded considerably in recent years. Highly penetrant genes that a re involved in familial cancer have been identified, but are likely to account for a relatively small proportion of total cancers. Other pre disposing genes have low penetrance, resulting in a moderate increase in the risk of specific cancers, but are widespread in the general pop ulation. This is the case for so-called metabolic polymorphisms. Scien tific interest in metabolic polymorphisms is based on the possibility of identifying subgroups of the population which are at elevated risk of developing environmentally-induced cancer. However, such studies ra ise a series of problems that are methodological - related to the stud y design and analysis - and ethical - related to the practical use tha t can be made of genetic information. This volume deals thoroughly wit h such problems.

Author: Nigel Trevellyan Brockton
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Author: Noha Sharafeldin
Publisher:
ISBN:
Category : Cancer
Languages : en
Pages : 172

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Genetic association studies have adopted for a long time a traditional analytic approach that focuses on individual genetic markers, usually single nucleotide polymorphisms (SNPs), in association with disease or phenotype. A standard single-SNP analysis that ignores combined effects of multiple SNPs and furthermore their interactions with environmental exposures, explains a small portion of disease heritability: an often cited issue of 'missing heritability'. A comprehensive approach that accounts for these interactions carries the potential for identifying novel susceptibility loci and is more suited to decipher causal relationships and underlying molecular mechanisms of disease. The overall goal of this dissertation is to develop a methodologically sound framework that examines interactions in genetic association studies that is able to represent the biologic underpinnings of disease and yield interpretations that are statistically valid and of clinical and/or public health relevance. We first examined interactions between genetic variants at the gene level in genome-wide association study (GWAS) data of six common chronic diseases of the Wellcome-Trust-Case-Control-Consortium (WTCCC): bipolar disorder (BD); coronary artery disease (CAD); hypertension (HT); rheumatoid arthritis (RA); type 2 diabetes (T2D); and type 1 diabetes (T1D). We used logic regression to search for biologically plausible forms of SNP-set interactions within genes. Next, we extended our approach to test for gene-environment interaction (GEI) effects at the pathway level and applied it to the population-based case-control data of the Diet, Activity and Lifestyle as a Risk Factor for Colorectal Cancer Study. We focused on the candidate pathway of angiogenesis and three hypothesized environmental exposures: dietary protein intake; smoking; and alcohol consumption. Our approach consisted of 3-steps: the first two summarized the within gene effects and the full pathway effects; and the third step modelled the GEI effects on colon and rectal cancer risk and survival. Our interaction analysis was able to detect an appreciable number of susceptibility loci showing strong evidence of association with the six diseases in WTCCC, including novel signals supported by biologically plausible links to the diseases. The number of genes with strong evidence of association was: 13 for BD; 16 for CAD; 15 for HT; 72 for RA; 105 for T1D; and 19 for T2D. The top significant genes were: NFIA with BD, CDKN2B with CAD, COL4A4 with HT, BTNL2 with RA, and TCF7L2 with T2D. The majority of strong single-SNP signals of WTCCC and on average 46% of recent GWAS meta-analyses signals were confirmed in our analysis. The results of the GEI pathway analysis also yielded an appreciable number of significant and novel interactions. Overall the magnitudes of gene interaction odds and hazard ratios increased with increasing levels of the interacting environmental exposure. This observed positive gradient supported the plausibility of the interactions. We found five statistically significant GEIs associated with colon cancer risk and three GEIs with colon cancer survival involving all three environmental exposures. For rectal cancer, we found eight significant GEIs in association with risk involving six genes and five GEIs with survival. This dissertation showed how exploring interactions of all measured SNPs within each gene can identify appreciable numbers of novel susceptibility loci in GWAS. We also showed that GEI effects on colorectal cancer risk and survival can be identified by adopting a comprehensive candidate pathway approach that emphasizes the biologic hypothesis in the selection of the pathway genes and environmental exposures and carries that logic through the analysis.

Author: Aga Syed Sameer
Publisher: Springer Nature
ISBN: 9813366990
Category : Medical
Languages : en
Pages : 353

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This book discusses the role of genetic polymorphism in susceptibility to cancers. The book explores the understanding of differences between the genetic polymorphisms and mutations.It reviews the mechanisms underlying the effect of polymorphism in genes encoding proteins that play an essential role in metabolism, signal transduction, cell cycle, and DNA repair mechanisms. Further, it investigates various techniques that are used for analyzing the genetic polymorphisms. The book contains many chapters which summarize the importance of genetic information obtained from polymorphism-based pharmaco-genetic tests to predict better drug response and life-threatening adverse reactions to chemotherapeutic agents, help in understanding of the impact of SNPs on gene function, and gives overview of the different SNP databases for examination. This book, therefore, serves as an essential guidebook for independent researchers as well as institutions working in this specialised field.

Author: Brendan Lee
Publisher: Oxford Monographs on Medical G
ISBN: 0199797587
Category : Medical
Languages : en
Pages : 393

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This volume is an expansion on the known treatment model of IEMs, one that establishes an innovative pathway approach and provides a new authority on this family of disease. Alongside the standard cadre of molecular and clinical underpinnings, this book includes coverage of newborn screening and an overarching treatment of IEMs as complex diseases.

Author: United States. Public Health Service. Office of the Surgeon General
Publisher:
ISBN:
Category : Government publications
Languages : en
Pages : 728

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This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.

Author: Miguel A. Rodriguez-Bigas
Publisher: Springer Science & Business Media
ISBN: 144196603X
Category : Medical
Languages : en
Pages : 615

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Colorectal cancer is the third most commonly diagnosed cancer in the US and the third most recently linked to cancer deaths. The national annual incidence rate of colorectal cancer is approximately 148,000+, striking slightly more females than males. The lifetime risk of colorectal cancer is 5-6%, however patients with a familial risk (with two or more first or second degree relatives) make up 20% of the patients. Persons who carry genetic mutations linked to hereditary colorectal cancer are the most likely to develop the disease.

Author: Trygve Tollefsbol
Publisher: Academic Press
ISBN: 012375710X
Category : Science
Languages : en
Pages : 639

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Book Description
Epigenetics is considered by many to be the "new genetics" because of the overwhelming evidence of the contribution of non-genetic factors such as nutrition, environment, and chemical exposure on gene expression. The effects of epigenetics are vast, including tissue/organ regeneration, X-chromosome inactivation, and stem cell differentiation and genomic imprinting and aging. Aberrations of epigenetics influence many diseases for which clinical intervention is already in place, and many novel epigenetic therapies for cancer, immune disorders, neurological and metabolic disorders, and imprinting diseases are on the horizon. This comprehensive collection of reviews written by leaders in the field of epigenetics provides a broad view of this important and evolving topic. From molecular mechanisms and epigenetic technology to discoveries in human disease and clinical epigenetics, the nature and applications of the science will be presented for those with interests ranging from the fundamental basis of epigenetics to therapeutic interventions for epigenetic-based disorders. Contributions by leading international investigators involved in molecular research and clinical and therapeutic applications Integrates methods and biological topics with basic and clinical discoveries Includes coverage of new topics in epigenetics such as prions, regulation of long-term memory by epigenetics, metabolic aspects of epigenetics, and epigenetics of neuronal disorders