Thesis (Ph.D.)--University of Washington, 2012

Stott-Miller, Marni

Thesis (Ph.D.)--University of Washington, 2012Abnormalities of glucose metabolism, such as impaired glucose tolerance and diabetes, have been associated with increased risk of multiple types of cancers. Similarly, metabolic syndrome, which is a cluster of health abnormalities including impaired fasting glucose, has been found to increase the risk of various cancers. Whether abnormal glucose metabolism is associated with risk of head and neck squamous cell carcinoma (HNSCC) has received little attention. To address this, we conducted three studies. First, we examined whether self-reported history of diabetes was associated with head and neck cancer in a pooled analysis of case-control studies. Second, we tested whether medical administrative records of type II diabetes or metabolic syndrome were associated with HNSCC using data from the SEER-Medicare database. Third, we compared gene expression profiles of oral squamous cell carcinoma (OSCC) and normal oral tissue from controls with respect to pathways and genes involved in glucose metabolism. In the pooled analysis, we observed a weak association between diabetes and head and neck cancer overall (OR=1.09; 95% CI: 0.95-1.24), but a modest association among never smokers (OR=1.59; 95% CI: 1.22-2.07) and no association among ever smokers. In the second study, we observed a marginal inverse association between type II diabetes and HNSCC (OR=0.92; 95% CI: 0.88-0.96) and a moderate inverse association for metabolic syndrome (OR=0.81; 95% CI: 0.78-0.85). We observed differential expression between normal tissue and OSCC, as well as dysplastic tissue, for pathways and genes involved in glucose metabolism. Contrasting results from the first two studies make conclusions about the role of diabetes and/or metabolic syndrome in HNSCC difficult. However, it is likely that results from the pooled study were closest to the truth, as we were better able to stratify by risk factors and adjust for important potential confounders. The third study provided some molecular evidence that glucose metabolism abnormalities play a role in HNSCC. Prospective studies incorporating biomarkers are needed to improve our understanding of the relationship between diabetes and HNSCC, possibly providing new prevention strategies. As rates of glucose metabolism abnormalities increase worldwide, even a small impact on HNSCC risk is of public health concern

Abnormal glucose metabolism and metabolic syndrome in the etiology of head and neck squamous cell carcinoma (HNSCC)

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