{"id":{"repo_id":"arizona-thes","oai_identifier":"oai:repository.arizona.edu:10150/193888"},"canonical_url":"https://search.dev.ndltd.org/etd/arizona-thes/oai:repository.arizona.edu:10150/193888","repository":{"repo_id":"arizona-thes","name":"University of Arizona","base_url":"https://repository.arizona.edu/oai/request"},"display":{"title":"Using Genetic Epidemiologic Methods to Explore the Influence of Gene-Environment Interactions on Colorectal Adenoma Recurrence","abstract":"Introduction: There is evidence to suggest that common genetic polymorphisms can modify the effect of environmental risk factors on colorectal neoplasia. Methods: Data on 1430 individuals were obtained from two chemoprevention trials, the Wheat Bran Fiber Trial (WBF) (1) and the Effects of Ursodeoxycholic Acid on Adenomatous Polyp Recurrence Trial (URSO) (2). Data were analyzed to test for gene-environment interactions between allelic variation in PPAR-γ (Pro12Ala, C1431T), body mass index (BMI) and waist circumference, and the biochemical biomarkers of metabolic syndrome. Simulated data were then used to determine if the sample size required to formally test the relationship between gene-exposure interactions could be reduced by using a genetically enriched study population. For this simulation aspect of the work, an established gene-drug interaction (i.e.: flavin monooxygenase 3 (FMO3) and sulindac) was used as a model system. Results: There was a borderline significant interaction between BMI and PPAR-γ for the Pro12Ala genotype (p(inter)=0.11) and significant interactions between BMI and the C1431T genotype (p(inter)=0.09). Results from the recursive partition model identified BMI (p = 0.007) and baseline fasting glucose levels (p =0.033) as significant predictors of colorectal adenoma recurrence for carriers of Ala12 and waist circumference as a significant predictor for the Pro12Pro12 carriers (p=0.002). Results from the simulated studies indicated that using genetically pre-screened and enriched populations can result in a 50% savings in the number of subjects required to test the candidate gene-drug interaction. Conclusions: These findings provide evidence that the effect of allelic variation in PPAR-γ on colorectal adenoma recurrence is modified by BMI and that component traits of metabolic syndrome differentially affect the risk of colorectal adenoma recurrence depending on genotype. In addition, using genotype as an inclusion criterion in future studies of adenoma recurrence will result in a smaller sample size required to test gene-environment interactions.","abstract_html":"Introduction: There is evidence to suggest that common genetic polymorphisms can modify the effect of environmental risk factors on colorectal neoplasia. Methods: Data on 1430 individuals were obtained from two chemoprevention trials, the Wheat Bran Fiber Trial (WBF) (1) and the Effects of Ursodeoxycholic Acid on Adenomatous Polyp Recurrence Trial (URSO) (2). Data were analyzed to test for gene-environment interactions between allelic variation in PPAR-γ (Pro12Ala, C1431T), body mass index (BMI) and waist circumference, and the biochemical biomarkers of metabolic syndrome. Simulated data were then used to determine if the sample size required to formally test the relationship between gene-exposure interactions could be reduced by using a genetically enriched study population. For this simulation aspect of the work, an established gene-drug interaction (i.e.: flavin monooxygenase 3 (FMO3) and sulindac) was used as a model system. Results: There was a borderline significant interaction between BMI and PPAR-γ for the Pro12Ala genotype (p(inter)=0.11) and significant interactions between BMI and the C1431T genotype (p(inter)=0.09). Results from the recursive partition model identified BMI (p = 0.007) and baseline fasting glucose levels (p =0.033) as significant predictors of colorectal adenoma recurrence for carriers of Ala12 and waist circumference as a significant predictor for the Pro12Pro12 carriers (p=0.002). Results from the simulated studies indicated that using genetically pre-screened and enriched populations can result in a 50% savings in the number of subjects required to test the candidate gene-drug interaction. Conclusions: These findings provide evidence that the effect of allelic variation in PPAR-γ on colorectal adenoma recurrence is modified by BMI and that component traits of metabolic syndrome differentially affect the risk of colorectal adenoma recurrence depending on genotype. In addition, using genotype as an inclusion criterion in future studies of adenoma recurrence will result in a smaller sample size required to test gene-environment interactions.","abstract_has_math":false,"creators":["Lowe, Kimberly Anne"],"institution":"The University of Arizona.","degree_name":"PhD","degree_level":"doctoral","degree_discipline":"Epidemiology","degree_department":null,"school":null,"contributors":[],"advisors":["Martinez, M. Elena"],"committee_chairs":[],"committee_members":["Ranger-Moore, James","Sherrill, Duane","Guerra, Stefano","Thompson, Patricia"],"year":2008,"date_issued":"2008","date_published":"2008","updated_at":"2026-07-24T00:56:22Z","subjects":["genetic epidemiology","gene-environment interactions","colorectal adenoma recurrence"],"languages":["EN"],"rights":["Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10150/193888","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Martinez, M. Elena"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Ranger-Moore, James","Sherrill, Duane","Guerra, Stefano","Thompson, Patricia"]},{"key":"dc:creator","label":"Author","values":["Lowe, Kimberly Anne"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2011-12-05T22:07:25Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2011-12-05T22:07:25Z"]},{"key":"dc:date.issued","label":"Date","values":["2008"]},{"key":"dc:publisher","label":"Institution","values":["The University of Arizona."]},{"key":"dc:type","label":"Dc Type","values":["text","Electronic Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Epidemiology","Graduate College"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["PhD"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Arizona"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["genetic epidemiology","gene-environment interactions","colorectal adenoma recurrence"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["EN"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10150/193888"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Introduction: There is evidence to suggest that common genetic polymorphisms can modify the effect of environmental risk factors on colorectal neoplasia. Methods: Data on 1430 individuals were obtained from two chemoprevention trials, the Wheat Bran Fiber Trial (WBF) (1) and the Effects of Ursodeoxycholic Acid on Adenomatous Polyp Recurrence Trial (URSO) (2). Data were analyzed to test for gene-environment interactions between allelic variation in PPAR-γ (Pro12Ala, C1431T), body mass index (BMI) and waist circumference, and the biochemical biomarkers of metabolic syndrome. Simulated data were then used to determine if the sample size required to formally test the relationship between gene-exposure interactions could be reduced by using a genetically enriched study population. For this simulation aspect of the work, an established gene-drug interaction (i.e.: flavin monooxygenase 3 (FMO3) and sulindac) was used as a model system. Results: There was a borderline significant interaction between BMI and PPAR-γ for the Pro12Ala genotype (p(inter)=0.11) and significant interactions between BMI and the C1431T genotype (p(inter)=0.09). Results from the recursive partition model identified BMI (p = 0.007) and baseline fasting glucose levels (p =0.033) as significant predictors of colorectal adenoma recurrence for carriers of Ala12 and waist circumference as a significant predictor for the Pro12Pro12 carriers (p=0.002). Results from the simulated studies indicated that using genetically pre-screened and enriched populations can result in a 50% savings in the number of subjects required to test the candidate gene-drug interaction. Conclusions: These findings provide evidence that the effect of allelic variation in PPAR-γ on colorectal adenoma recurrence is modified by BMI and that component traits of metabolic syndrome differentially affect the risk of colorectal adenoma recurrence depending on genotype. In addition, using genotype as an inclusion criterion in future studies of adenoma recurrence will result in a smaller sample size required to test gene-environment interactions."]},{"key":"dc:title","label":"Title","values":["Using Genetic Epidemiologic Methods to Explore the Influence of Gene-Environment Interactions on Colorectal Adenoma Recurrence"]}]}],"canonical_facts":{"dc:contributor.advisor":["Martinez, M. Elena"],"dc:contributor.committeemember":["Ranger-Moore, James","Sherrill, Duane","Guerra, Stefano","Thompson, Patricia"],"dc:creator":["Lowe, Kimberly Anne"],"dc:date.accessioned":["2011-12-05T22:07:25Z"],"dc:date.available":["2011-12-05T22:07:25Z"],"dc:date.issued":["2008"],"dc:description.abstract":["Introduction: There is evidence to suggest that common genetic polymorphisms can modify the effect of environmental risk factors on colorectal neoplasia. Methods: Data on 1430 individuals were obtained from two chemoprevention trials, the Wheat Bran Fiber Trial (WBF) (1) and the Effects of Ursodeoxycholic Acid on Adenomatous Polyp Recurrence Trial (URSO) (2). Data were analyzed to test for gene-environment interactions between allelic variation in PPAR-γ (Pro12Ala, C1431T), body mass index (BMI) and waist circumference, and the biochemical biomarkers of metabolic syndrome. Simulated data were then used to determine if the sample size required to formally test the relationship between gene-exposure interactions could be reduced by using a genetically enriched study population. For this simulation aspect of the work, an established gene-drug interaction (i.e.: flavin monooxygenase 3 (FMO3) and sulindac) was used as a model system. Results: There was a borderline significant interaction between BMI and PPAR-γ for the Pro12Ala genotype (p(inter)=0.11) and significant interactions between BMI and the C1431T genotype (p(inter)=0.09). Results from the recursive partition model identified BMI (p = 0.007) and baseline fasting glucose levels (p =0.033) as significant predictors of colorectal adenoma recurrence for carriers of Ala12 and waist circumference as a significant predictor for the Pro12Pro12 carriers (p=0.002). Results from the simulated studies indicated that using genetically pre-screened and enriched populations can result in a 50% savings in the number of subjects required to test the candidate gene-drug interaction. Conclusions: These findings provide evidence that the effect of allelic variation in PPAR-γ on colorectal adenoma recurrence is modified by BMI and that component traits of metabolic syndrome differentially affect the risk of colorectal adenoma recurrence depending on genotype. In addition, using genotype as an inclusion criterion in future studies of adenoma recurrence will result in a smaller sample size required to test gene-environment interactions."],"dc:identifier.uri":["http://hdl.handle.net/10150/193888"],"dc:language.iso":["EN"],"dc:publisher":["The University of Arizona."],"dc:rights":["Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author."],"dc:subject":["genetic epidemiology","gene-environment interactions","colorectal adenoma recurrence"],"dc:title":["Using Genetic Epidemiologic Methods to Explore the Influence of Gene-Environment Interactions on Colorectal Adenoma Recurrence"],"dc:type":["text","Electronic Dissertation"],"thesis:degree_discipline":["Epidemiology","Graduate College"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["PhD"],"thesis:institution_name":["University of Arizona"]},"updated_at":"2026-07-24T00:56:22Z"}