Adult body mass and weight gain over the lifecourse and risk for postmenopausal breast cancer and endometrial cancer.

Overweight and obesity are well-established risk factors for breast and endometrial cancer in postmenopausal women. It has been speculated that the increased risk associated with increased adiposity is related to changes in the internal hormonal environment that stimulates proliferation of both normal and neoplastic cells. It has been hypothesized that adult weight gain, because it is primarily a gain in fat mass, is a superior surrogate measure of adult adiposity compared to absolute weight or body mass index, as these more commonly used correlated measures are unable to distinguish fat mass from lean body mass. Most studies of adult weight gain and breast cancer in postmenopausal women have suggested a positive relationship beyond the contribution to overall body weight. However, because these studies in general have not examined weight change across the life span, they may have overlooked potentially critical periods in which target tissues may be more sensitive to endogenous hormonal exposures. This study examined the relationship between weight gain at different points in time and risk of postmenopausal breast and endometrial cancer, as well as potential interactions between body size and hormonal risk factors and diabetes. The results of this dissertation indicated that weight gain, particularly weight gain in the decade prior to diagnosis, was associated with an increased risk of breast cancer in postmenopausal women. Moreover, the risk of breast cancer associated with weight gain was enhanced among overweight women and most apparent in women who reported never using postmenopausal hormones. Adult weight gain was not associated with risk of endometrial cancer independently of the impact on body weight. Furthermore, it was observed that the odds of developing endometrial cancer among women who were both diabetic and obese was much greater compared to women who were either obese or diabetic, suggesting an interaction between these two risk factors. The results of this study provide further evidence that increased body weight is a significant predictor of risk of breast and endometrial cancer and suggest that weight maintenance in non-overweight women and weight loss in overweight and obese women may be an important strategy in the primary prevention of both breast and endometrial cancer.Ph.D.Health and Environmental SciencesPublic healthUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/127144/2/3029294.pd