Aim 3: Risk Analysis
Determine if increased endogenous or exogenous hormones at different points in development alters the risk of gynecologic cancer
In our risk analysis, we will determine whether a person's risk of gynecologic cancer is affected by certain estrogen exposure during early fetal development. Several epidemiologic studies have suggested that high birth weight, the presence of an obstetrical complication called pre-eclampsia, preterm delivery and other conditions that are associated with high estrogen levels during pregnancy are associated with an increased risk of breast cancer as an adult.
In collaboration with Norwegian co-investigators, we are investigating the effects of obstetrical conditions (characterized by high estrogen levels) on the risk of adult onset endometrial cancer using Scandanavian birth and cancer registries.
The epidemiologic investigation is being complemented by experiments using transgenic mice (PTEN+/PTEN-) that are aimed at determining the effects of different exogenous estrogens given at different time points during pregnancy on the risk of future endometrial cancer risk. In addition the modulation of endogenous estrogens through variations in diet is being examined in the transgenic mice to identify effects on endometrial cancer risk. The mice will be examined using both magnetic resonance imaging as well as pathologic and microarray analysis of endometrial analysis of endometrial tissues harvested at necropsy.