This project covers a broad base of studies aimed at assessing the epidemiology of the majority of hormonally-related cancers. Major efforts are underway for breast, endometrial, ovarian, and testicular cancers. We also have an active research program on prostate cancer, covered in a separate report (Z01 CP010180-02). Our efforts for all of these cancers relate to a variety of environmental, genetic and hormonal predictors of risk.[unreadable] [unreadable] A large multi-disciplinary study has been completed in Poland to assess risk factors for breast, ovarian and endometrial cancers. The study involved collection of multiple biologic samples, with a primary aim of assessing the interactive effects of genetic and environmental determinants of risk. In addition, special components of the study addressed effects of physical activity, occupational factors, and household chemical exposures. For physical activity, special efforts were expended to improve exposure assessment, with women being asked to wear accelerometers to obtain more objective measures than interview data alone. The study also involved collection of tissue samples to enable precise tumor classification as well as assays of tumor biomarkers (including utilizing newly developed tissue microarray techniques). The large amount of data collected in this investigation are enabling a number of analyses. With respect to breast cancer, analyses are currently underway to assess effects of occupational exposures, physical activity levels, anthropometric factors, perinatal exposures, and etiologic heterogeneity by tumor stage and hormone receptor status.[unreadable] [unreadable] Another large case-control study, focused on breast cancer, has involved collection of buccal cell specimens. This effort required extensive methodologic work to determine the optimal means of collecting, processing and storing samples in order to maximize DNA yield. Breast cancer risk is also of major interest in a follow-up of a cohort of women previously screened for bone density. This resource, which previously involved collection of serologic samples and currently is collecting buccal swabs, will enable an assessment of the interrelationship of bone density, genetic factors and endogenous hormones in predicting subsequent cancer occurrence.[unreadable] [unreadable] A collaboration has recently been established with the Gynecologic Oncology Group to determine means of collecting epidemiologic data within the context of a number of ongoing trials. A standardized questionnaire has been developed and has been integrated into a large trial of endometrial. This effort should be useful in assessing epidemiologic predictors and molecular markers associated with carefully defined histologic subgroups of tumors. It is hoped that this questionnaire can be integrated into trials of other cancer sites and that additional more targeted questionnaires can be developed to address specific hypotheses of interest to gynecologic oncologists. [unreadable] [unreadable] We have learned much about the natural history of cervical cancer (as described in another project report) and are now anxious to expand our knowledge in this area to address the natural history of another gynecologic tumor, namely endometrial cancer. Endometrial hyperplasias are recognized as predisposing to risk but many unresolved questions remain regarding intervening effects of other risk predictors. We have launched an exploratory effort within a prepaid health plan to determine the feasility of initiating a larger scale study on the topic. We are also in the pilot phases of developing a study to assess early markers which may be important to the development of ovarian and endometrial cancers. This study involves the collection of ovarian and endometrial tissues from patients undergoing a variety of gynecologic conditions; tissue samples will be linked with epidemiologic data to determine markers which may correlate with the future occurrence of malignancies.