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Effect of dietary glycemic load and single nucleotide polymorphisms in the adipogenesis pathway on colon cancer susceptibility

Zelenskiy, Svetlana
http://rave.ohiolink.edu/etdc/view?acc_num=case1386349030

Abstract Details

2014, Doctor of Philosophy, Case Western Reserve University, Epidemiology and Biostatistics.
Background: Colorectal cancer is one of the most potentially curable and preventable of gastrointestinal cancers (2) with dietary and other modifiable factors accounting for approximately 90% of colorectal tumors (3, 4). Insulin resistance is proposed to underlie many of the lifestyle risk factors-colon cancer associations and high incidence rates of colon cancer in developed countries (5). The insulin resistance-colon cancer hypothesis postulates that many independent risk factors for colon cancer lead to hyperinsulinemia, and excess of insulin in turn promotes colon carcinogenesis. Genetic influence also affects colon carcinogenesis. Objectives: Therefore, this dissertation examined whether genetic variants in the adipogenesis pathway, alone or in combination with environmental risk factors, affect colon cancer risk among residents of the Kentucky state. Aim 1 assessed the association of dietary glycemic load (GL) and colon cancer risk. Aim 2 examined the association of single nucleotide polymorphisms (SNPs) and haplotypes in leptin, adiponectin, and PPAR-γ genes with colon cancer risk. Aim 3 explored colon cancer risk when latent constructs of each gene and environmental risk factors were modeled simultaneously using structural equation modeling (SEM). Methods: Associations of colon cancer risk with genetic and environmental risk factors were examined in a population-based case-control study, conducted in the state of Kentucky between April 2003 and December 2010. Participants donated blood sample and completed a self-administered lifestyle risk factor questionnaire (RFQ) and Arizona Food Frequency Questionnaire (AFFQ). Descriptive statistics, logistic regression analyses, and SEM were performed to describe colon cancer risk factors and measure their impact on cancer risk. Results: Consumption of high GL diet significantly increased individual’s risk of colon cancer, and this association was modified by age. A total of eight variants, representing all three genes, and haplotype analysis revealed statistically significant associations with colon cancer risk. Leptin may not be solely responsible for increased risk of cancer, but becomes a risk factor in the presence of other genes. Conclusions: Low GL diet could be a potential preventive measure against colon cancer risk. Identified polymorphisms could serve as biomarkers to identify high risk individuals through genetic screening in order to help tailor prevention strategies.
Daniel Tisch (Committee Chair)
Li Li (Advisor)
Cheryl Thompson (Committee Member)
Mark Schluchter (Committee Member)
171 p.
Biostatistics; Epidemiology; Oncology; Public Health
Diet; glycemic load; single nucleotide polymorphisms; adiponectin; leptin; PPAR-gamma; structural equation modeling; insulin resistance; colon cancer

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Citations

  • Zelenskiy, S. (2014). Effect of dietary glycemic load and single nucleotide polymorphisms in the adipogenesis pathway on colon cancer susceptibility [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1386349030

    APA Style (7th edition)

  • Zelenskiy, Svetlana. Effect of dietary glycemic load and single nucleotide polymorphisms in the adipogenesis pathway on colon cancer susceptibility. 2014. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1386349030.

    MLA Style (8th edition)

  • Zelenskiy, Svetlana. "Effect of dietary glycemic load and single nucleotide polymorphisms in the adipogenesis pathway on colon cancer susceptibility." Doctoral dissertation, Case Western Reserve University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1386349030

    Chicago Manual of Style (17th edition)

case1386349030
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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.