Genetic Susceptibility to Endometrial Cancer

Endometrial cancer, cancer of the epithelial lining of the uterine corpus, is the most common gynecological malignancy in the United States and is the eighth leading cause of cancer death in U.S. women. The endometrium is highly responsive to hormonal stimuli; cyclic production of estrogen and progesterone during the menstrual cycle, and declining sex steroid levels after menopause are correlated with endometrial proliferation and/or atrophic morphological changes. Excess exposure to endogenous and exogenous estrogens, unopposed by progesterone, increases endometrial cell division and is suggested to be the mechanism through which established risk factors for endometrial cancer influence risk. In searching for endometrial cancer susceptibility genes, components of the sex steroid hormone pathway are likely candidates. Data suggest that sequence variations within genes involved in the sex steroid hormone pathway may be responsible for altered levels of steroid hormones and hormone metabolites, and hence, associated with an increased risk of endometrial cancer. A number of molecular epidemiological studies have been conducted to evaluate associations between variations within genes involved in the steroid hormone pathway and endometrial cancer risk. In this report, we review the role of sequence variations within the genes encoding for proteins involved in sex steroid biosynthesis, metabolism, and transport in modulating individual susceptibility to endometrial cancer.