About the Branch
Overview
The Hormonal and Reproductive Epidemiology Branch conducts research to identify groups at high risk of cancer, clarify the natural history of various cancers, understand the interactive effects of genetic and environmental factors on cancer risk, and elucidate biologic mechanisms of carcinogenesis.
To identify risk factors for hormonally-related tumors, we assess:
- Reproductive and family history,
- Endogenous hormones,
- Exogenous hormones (oral contraceptives and menopausal hormones),
- Hormonal correlates of risk, and
- Conditions related to marked hormonal perturbations, such as infertility and endometriosis.
Another major area of research is focusing on the role of the human papillomaviruses in the etiology of genital tumors. Emphasis is also being given to defining risk factors for several rare malignancies, including cancers of the nasopharynx and biliary tract. Investigations are often preceded by methodologic studies to determine the best approaches to specific study-related issues.
Breast Cancer
Several major research efforts are focusing on assessing gene-environment interactions in two large case-control studies, one in two areas of Poland and the other in three U.S. centers. Biologic samples from these studies (buccal washes, blood samples) will be used to measure common polymorphisms in a variety of genes. Of interest will be genes involved in carcinogen and hormone metabolism as well as those involved with DNA repair mechanisms. It is hoped that by subdividing study subjects according to their ability to metabolize agents that it may be possible to clarify the role of a number of speculative environmental risk factors for breast cancer, including exogenous hormone use, alcohol consumption and cigarette smoking. The Poland study also involves collection of urine samples (which will be used to measure environmental chemicals) and breast tissue (for which microarray techniques will be used to assess a variety of biologic markers which may provide insights into mechanisms of carcinogenesis).
The effects of endogenous hormones have been investigated by studying cancer risks associated with a number of conditions related to hormonal perturbations, such as endometriosis and other gynecologic disorders, and by directly measuring hormone levels in analytic studies. Following a number of methodologic studies, several investigations are examining the relationship of a variety of hormones, including estrogen and androgen metabolites, to breast cancer risk. In addition, studies are investigating growth factors that influence hormone levels, such as insulin growth factors. Data from several of these studies are also being used to better understand how cancer risk factors relate to endogenous hormone levels.
Other Hormonally-Related Tumors: Endometrium and Ovary
A number of studies are attempting to identify risk factors for other malignancies affected by hormonal mechanisms. For endometrial and ovarian cancers, we are focusing on risk factors hypothesized to operate through hormonal mechanisms, such as obesity and physical activity. We also are interested in evaluating gene-environment interactions for these cancers and in identifying risk factor differences across specific pathologic subgroups. We are also assessing the effects of ovulation-stimulating drugs on ovarian and other cancers.
Prostate Cancer
Genetic and environmental determinants are being assessed in a population with rising rates. The role of endogenous hormones in prostate cancer risk is also being examined, and includes efforts to relate serologic hormone measurements with levels in prostate tissue. In addition, dietary influences on endogenous hormone levels are being evaluated using data from cross-sectional studies and clinical trials.
Human Papillomaviruses
A major objective of our interdisciplinary research activities is to clarify how human papillomaviruses (HPV) and host and environmental factors interrelate to influence the progression of cervical lesions to cancer. The major focus of this research are two large cohort studies, one in a low-risk setting (Portland, Oregon) and the other in a high-risk region (Guanacaste, Costa Rica). These studies provide the framework for gaining a better understanding the natural history of cervical lesions with respect to HPV, especially the influence of immunologic and hormonal factors. Clarifying the pathogenesis of this disease is being approached on four levels: (1) the molecular pathogenesis of progression to carcinoma in situ and on to invasive cancer, (2) microscopic pathogenesis using new computer-assisted cytologic techniques, (3) visual pathogenesis using new optical-galvanic examination techniques, and (4) immunologic assessment using serology and cell-mediated immune assays. The influence of HPV on cancer risk at other sites is also of research interest, especially for rare female reproductive tumors, such as cancers of the vulva and vagina, as well as cancers of the penis, esophagus, and oral cavity.
Rare Malignancies
Case-control studies are being conducted to advance our knowledge about the etiology of rare, poorly understood cancers. The studies are often conducted in foreign settings, where the cancers are more common or there are unusual relevant risk factors. Recent studies include investigations of nasopharyngeal cancer in Taiwan and biliary tract cancer in China. Attempts are made to clarify the interplay of genetic and environmental influences through analyses of risk factor information and genetic polymorphisms, endogenous hormones, specific metabolites, and tumor markers.
Testicular
Testicular germ cell cancer has been increasing among men during most of the 20th century. Despite this increase, the etiology of testicular cancer is poorly understood. To better understand the molecular epidemiology of testicular cancer, the National Cancer Institute and the Department of Defense are conducting a case-control study of testicular cancer among military servicemen. The project includes obtaining biosamples and questionnaire data from all participants. Pre-diagnostic serum samples are available from the approximately 1,100 cases and 1,100 controls enrolled in the study. Mothers of all participants are also invited to participate by donating a biosample and responding to a questionnaire.
Methodologic Studies
Many of our studies require methodologic work to determine the appropriate epidemiologic approach or biochemical adjuncts for large-scale efforts. This work includes attempts to reduce errors in exposure and disease classification, as well as to improve statistical approaches to study designs. In some research areas, such as with HPV, methods work evolved into limited diagnostic research. In the area of endogenous hormones, measurement assays have been assessed to determine their reliability and validity for use in analytic epidemiologic studies.
