by Amy Stone laine Flagg's interests in nutrition, the environment, and health began overlapping long ago. With an undergraduate degree in chemistry, Flagg, now an assistant professor at the Rollins School of Public Healt h, worked for several years as a laboratory chemist for the Environmental Protection Agency. Later, on the West Coast, she began developing working relationships with herbalists and others in the natural foods industry. At one point, Flagg even worked as a chef in a health food restaurant. As Flagg grew more interested in the field of nutrition, she returned to school to gain more expertise. After completing a master's degree at the University of Georgia, she enrolled in a doctoral program in epidemiology at the Rollins School of Public Health. Her dissertation examined the role of glutathione in the plasma and diet of humans. Flagg showed that glutathione, which acts as an antioxidant and helps metabolize toxins, may be protective against oral cancer when it is ingested from fruit and v egetable sources. Today, Flagg's interests happily coexist in research studies that focus on the impact of nutrition and the environment on health. A faculty member at the school since 1992, she is currently engaged in a number of projects that examine the role of nutri tion in many forms of cancer, including breast, ovarian, and prostate cancers, as well as melanoma. She targets much of her research toward understanding how the complexities of people's environments put them at risk for certain types of cancer.

tudying a person's exposure to certain foods or chemicals is often an inexact endeavor, since the researcher has to rely not only on subjects' recall but also on their truthfulness in answering questions. Am ong Flagg's arsenal of approaches are retrospective studies that ask research participants to recall prior events, which then help investigators search for common links to the disease under study. "In several studies, when asking subjects to recall past e vents, such as exposure to agricultural chemicals or exogenous hormones, we use a life events calendar, which uses both national events relevant to the study group and personal events or milestones to help jog memories," Flagg says. "The key is to create a list of events to which the subjects can relate." Flagg's most recent project is the development of a questionnaire for a large case control study of prostate cancer. The American Cancer Society estimates that 184,000 men will be diagnosed with prostate cancer in 1998, and approximately 39,200 men wil l die of it. The scenario is worse for African Americans, whose mortality rates of prostate cancer are about twice those of white men. Flagg and her colleagues in the departments of Epidemiology and Environmental and Occupational Health have created a det ailed life events calendar that examines past agricultural practices of farmers based on focus groups and pilot interviews in several counties in rural Georgia. Accompanying the calendar is a food frequency questionnaire that evaluates the current dietary practices of the farmers. A number of metropolitan Atlanta and rural Georgia counties are included in the Surveillance, Epidemiology, and End Results (SEER) registries, from which the researchers will draw their study sample. The National Cancer Institute established the SEER r egistry program in 1973. Because the Georgia cancer registry includes a large number of African Americans as well as whites with cancer, it offers unusual opportunities to study cancers that differentially affect African Americans and Caucasians, Flagg sa ys. Racial disparities in incidence and survival also exist in breast cancer.

One of Elaine Flagg's research interests is understanding the risk factors for the differences in aggressive and nonaggressive breast cancer. Here, a patient prepares for mammography.

hile some breast cancers act aggressively, spreading quickly to other parts of the body, others may remain localized for years. A prospective, case control study on which Flagg is collaborating will follow wo men who have invasive breast cancer that has spread to at least one node. "Being able to understand the differences between the types of cancer will help physicians develop treatment plans for individual patients," Flagg says. The researchers--who include physician William Eley in the school's Department of Epidemiology and other investigators at the Centers for Disease Control and Prevention and the Fred Hutchinson Cancer Research Center--will examine tumor tissue samples as well as medical records from 850 women, who participated in an earlier multi-site national trial known as the Women's Interview Study of Health. The current study uses molecular markers to search for the cellular stage of differentiation of normal cells into cancerous cells or the presence of the her2/neu oncogene, a known precursor to breast cancer. With the medical record information, the stu dy also will be able to account for personal characteristics, such as smoking or other risk-related behaviors. By following this group of women over a number of years, the researchers hope to associate risk factors with the development of the aggressive f orm of breast cancer. "We know that African-American women are more likely to develop aggressive disease at a younger age," Flagg says. "By seeing what is happening at the genetic and cellular levels in women with breast cancer, we may be able to tell if there is a biologic difference that accounts for this racial variation rather than, or in addition to, differences in access to care or behavioral factors." Flagg also is collaborating on a study that will supply important information to women taking either birth control pills or hormone replacement therapy, both of which are suspected to increase the risk of breast cancer. Flagg's contribution to the stud y is a life events calendar and a detailed questionnaire that will identify exposures to estrogen and reproductive experiences. These retrospective tools will help pinpoint the risk these factors pose to the development of cancer. This research is part of a national multi-site, study called the Women's Contraceptive and Reproductive Experiences study. Investigators are drawing the women with breast cancer from the SEER registry and selecting the control group from the national p opulation the registry covers. The large size of this study, coupled with the detail of the questionnaires, promises to provide solid information about the effects of exogenous hormones on a woman's risk of breast cancer, says Flagg.

Doctoral students working with Flagg include Robert Greenlee, who is investigating melanoma incidence, and Carolyn Monteilh, who is helping identify risk factors for aggressive breast cancer.