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dc.contributor.authorGogna, Priyanka
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date.accessioned2018-08-21T20:23:48Z
dc.date.available2018-08-21T20:23:48Z
dc.identifier.urihttp://hdl.handle.net/1974/24459
dc.description.abstractIntroduction: This study examined the association between established colorectal cancer (CRC) risk factors and LINE-1 DNA methylation in healthy colon tissue, and whether genes involved in one-carbon metabolism modify relationships between established CRC risk factors and LINE-1 DNA methylation. This study was undertaken in order to inform on the role of LINE-1 DNA methylation as a mechanism by which established risk factors may lead to carcinogenesis. Reduced LINE-1 DNA methylation and one-carbon metabolism-related gene variants are both shown to increase CRC risk. Exposures related to LINE-1 DNA methylation may have a greater effect on methylation levels for individuals already susceptible to reduced methylation due to possession of a genetic variant. When considered together, these effects may impact methylation patterns in individuals beyond what would be expected if effects were purely additive. Methods: The study population consisted of 317 individuals scheduled for a routine colonoscopy. Multivariable linear regression was used to study the associations of alcohol consumption, smoking, body mass index, non-steroidal anti-inflammatory drug use, physical activity, and fruit and vegetable consumption with LINE-1 DNA methylation. Product terms between MTHFR 677C>T (rs1801133), MTR 2756A>G (rs1805087), and MTRR 66A>G (rs1801394) genotypes and exposures of interest were used to examine effect modification by genotype. Results: There were no statistically significant relationships observed between each risk factor of interest and LINE-1 DNA methylation. Statistically significant interactions between alcohol consumption and MTHFR and MTR genotypes were observed (p-value interaction=0.009, 0.003) in relation to LINE-1 DNA methylation. Conclusion: This thesis presents novel results on the relationships between a comprehensive set of CRC risk factors and LINE-1 DNA methylation in healthy colon tissue. We observed significant interactions by gene variants in the relationships between CRC risk factors and LINE-1 DNA methylation in the healthy colon. Although effects were not consistently in hypothesized directions, they suggest that one-carbon metabolism-related gene status is an important effect modifier in the relationship between alcohol consumption and LINE-1 DNA methylation.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesCanadian thesesen
dc.rightsQueen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada*
dc.rightsProQuest PhD and Master's Theses International Dissemination Agreement*
dc.rightsIntellectual Property Guidelines at Queen's University*
dc.rightsCopying and Preserving Your Thesis*
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.*
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectEpidemiologyen_US
dc.subjectColorectal Canceren_US
dc.subjectDNA Methylationen_US
dc.titleInfluence of Environmental Risk Factors of Colorectal Cancer and Gene-Environment Interactions on Line-1 DNA Methylationen_US
dc.typethesisen
dc.description.degreeMaster of Scienceen_US
dc.contributor.supervisorKing, Will
dc.contributor.departmentPublic Health Sciencesen_US
dc.embargo.termsWe wish to publish both manuscripts in the submitted thesis, and do not want the work to be publicly accessible until after they individual chapters have been published.en_US
dc.embargo.liftdate2023-08-21T13:19:23Z
dc.embargo.liftdate2023-08-21T18:45:54Z


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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
Except where otherwise noted, this item's license is described as Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada