The Shanghai Endometrial Cancer Study (R01 CA92585) is thus far the largest population-based study of endometrial cancer, involving 1204 cases and 1212 controls. Over the past 6 years we have produced many significant, novel research findings from this study, particularly those related to soy food intake, tea consumption, genetic polymorphisms in the estrogen pathway, and gene-diet interactions in relation to the risk of endometrial cancer. In this renewal application, we propose to evaluate a new set of hypotheses related to the role of genetic variations in inflammation pathway genes in the developm ent of endometrial cancer. These genes were chosen because of the recently recognized critical role that inflammation and because of laboratory evidence indicating their interaction with estrogens and diet in the developm ent and progression of endometrial cancer. To reduce type I errors and enhance the statistical power of the study for gene-disease association studies, as well as gene-gene and gene-diet interactions, w e propose to recruit an additional 400 cases and 400 controls as part of this renewal proposal which will be used to validate all promising associations identified in the funding cycle and during the initial funding cycle. The proposed study, with its strong methodology and novel hypotheses, has great potential for discovering genetic markers and gene-d iet interactions that will be valuable for the prevention of endometrial cancer, one of the most common gynecological malignancies in the United States and many other parts of the world.
Chronic inflammation and miRNA may play a critical role in the development of endometrial cancer; constituents of soy and tea have been shown in experimental studies to have many anti-cancer properties, some of which are believed to act by regulating gene expression and thus may interact with inflammation genes and miRNA. The proposed study will comprehensively evaluate these hypotheses and the results will have a significant impact on endometrial cancer prevention among U.S. women, who are at high risk for endometrial cancer and whose consumption of soy food and tea has increased dramatically over the last decade.
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