Semester

Fall

Date of Graduation

2013

Document Type

Dissertation

Degree Type

PhD

College

School of Public Health

Department

Epidemiology

Committee Chair

Ian R. H. Rockett

Committee Co-Chair

Matthew J. Gurka

Committee Member

Joel A. Halverson

Committee Member

George A. Kelley

Committee Member

Juhua Luo

Abstract

Introduction: The prevalence of metabolic risk factors (MRFs), individually and in the aggregate, is growing rapidly. There is limited biologic and epidemiologic evidence indicating an association between MRFs and cancer. The goal of this dissertation was to examine the association between individual and combined MRFs with subsequent risk of overall and site-specific cancers of the breast, digestive system, and lung.;Methods: A systematic review with meta-analysis on the association between metabolic syndrome (a cluster of MRFs) and breast cancer was conducted. In addition, associations between MRFs and risk of overall and site-specific cancers were assessed by multivariable Cox proportional hazards regression models. Lastly, associations between MRFs and age at cancer onset were examined by multiple linear regression analyses, using the general linear model. Data were derived from the NHANES I Epidemiologic Follow-up Study, and comprised participants ages 25 to 74 years at baseline. The primary metabolic risk factors were obesity (measured by BMI), high blood pressure, high total serum cholesterol, and diabetes. Analyses were adjusted for age, race, education, family income, physical activity, smoking status, and family history of cancer, and stratified by age and gender. All analyses incorporated the complex sample design and sample weights to produce national estimates.;Results: Results from the meta-analysis show that metabolic syndrome was modestly associated with an increased risk for breast cancer in adult women. Findings from the study on the association between individual and combined MRFs and cancer risk suggest that diabetes independently, and presence of a combination of MRFs, may serve as markers for postmenopausal breast cancer risk. The association between diabetes and a combination of three or four MRFs and earlier age at onset was observed not only for postmenopausal breast cancer, but also for overall cancer in women 50 and older, digestive cancer in women, and lung cancer in males.;Conclusion: Future research needs to examine this association between MRFs and site-specific cancers using specific, objective metabolic markers. The positive association of MRFs with postmenopausal breast cancer points toward the need to develop public health strategies to manage these risk factors.;Keywords: Metabolic syndrome, metabolic risk factors, cancer, meta-analysis, breast cancer.

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