Dietary patterns, insulin-related factors, lifetime weight history, and endometrial cancer risk

Two datasets were used for this dissertation: a case-control study of endometrial cancer in the San Francisco Bay Area, and a prospective cohort study, the California Teachers Study, established in 1995. This dissertation consists of five chapters. The first chapter briefly describes endometrial cancer, its known risk factors, and an introduction to the topic of diet and obesity and their associations with endometrial cancer. The second chapter examines dietary patterns measured in different ways, and their impact on endometrial cancer risk in the case-control study. The third chapter examines dietary factors affecting insulin levels such as glycemic index, glycemic load, and fiber, and their association with endometrial cancer risk. The potential modification of these associations by presence of diabetes, obesity, and/or hypertension is also examined. These analyses are done in the California Teachers Study (CTS). The fourth chapter examines lifetime weight history and endometrial cancer risk in the casecontrol study including weight change, weight gain patterns, and body composition measures such as waist circumference, hip circumference, waist to hip, and waist to height ratio. The final chapter consists of concluding remarks.; This dissertation found that the "Western" dietary pattern identified through PCA was associated with a marginally significantly increased risk of endometrial cancer in a subgroup of non-supplement users; however, no other patterns were associated with risk overall or in subgroups. In addition, glycemic index(GI), glycemic load (GL), and fiber were not associated with endometrial cancer risk in the CTS. The effects of GI, GL, and fiber were not modified by the presence of obesity or hypertension. The findings of reduced risk estimates associated with higher glycemic load in those with diabetes or both obesity and hypertension are likely an artifact. Finally, with regard to lifetime weight history in the case-control study, substantial weight gain in adult life was associated with increased risk of endometrial cancer. In addition, persistent obesity throughout adulthood was associated with the highest risk of endometrial cancer, followed by obesity at later time points. Measures of body composition representing central obesity (waist circumference, waist to height ratio, and hip circumference) were associated with increased risk of endometrial cancer risk, independent of recent body mass index. The role of diet in endometrial cancer etiology is still unclear. While obesity is an established risk factor for endometrial cancer risk, investigations of body composition and patterns of weight loss and gain seek to clarify biological mechanisms.