Cancer Disparities: A Biological and Psychosocial Perspective
In 2003, four institutes at NIH, including NCI, funded eight Centers for Population Health and Health Disparities (CPHHD) to address this type of cross-disciplinary research, the cancer-related portions of which are overseen by staff in NCI's Division of Cancer Control and Population Sciences (DCCPS).
"These interrelated projects are scientifically ambitious because they address a more comprehensive set of pathways than traditional biomedical studies," says DCCPS Director Dr. Robert Croyle. "If the evidence suggests that looking at behavioral, environmental, and economic variables is an essential adjunct to biology, we may be on the way to resolving long-standing debates over which factors are necessary to account for health outcome disparities."
Four studies underway through the CPHHD initiative at the University of Chicago focus on the experience of 230 African American women living on Chicago's South Side who were newly diagnosed with breast cancer.
"Black women in the United States are twice as likely as whites to die from breast cancer that occurs before menopause," said Dr. Sarah Gehlert, who directs the CPHHD project at the University of Chicago. "This mortality gap has been known for years, but we haven't discovered any racial disparity in germ-line mutations for breast cancer - mutations that, in any case, don't explain even 10 percent of breast cancers," she adds.
Instead, since cancer is a multi-step process, she reasons that numerous health behaviors and environmental factors are likely to cause changes that are not inherited but can persist as cells divide. "Ultimately the CPHHD initiative and other trans-disciplinary studies will begin to point us to interventions that truly affect group health differences," she says.
In 2000 Dr. Suzanne Conzen, a colleague of Dr. Gehlert's at the University of Chicago, was looking into apoptosis - or induced cell suicide - in breast cancer. She reasoned that if mammary epithelial cells were proliferating abnormally, they must have found a pathway that enabled them to evade apoptosis and survive.
Research in her lab eventually showed that this survival pathway may be tied to glucocorticoids (GCs), neuroendocrine hormones produced when a person is under stress. "This surprised us," said Dr. Conzen, because GCs, which flood the body in response to stress, induce apoptosis in some cell types, an observation that has been exploited in the treatment of lymphomas.
However, in experiments with breast epithelial cancer cell lines, Dr. Conzen's lab found that prolonged exposure to elevated GC concentrations inhibited apoptosis through the activation of GC receptors, which was then associated with the expression of several "survival genes" - SGK1 and MKP1, for example - that interfered with apoptosis.
But further insight may be gained by looking at social factors, such as the neighborhoods the women live in, explained Dr. Gehlert. "We're only beginning to understand the causal pathways through which social context contributes to health disparities," she said.
At the community level, many studies have documented an association between neighborhood context - including the rates of violent crimes, the lack of, or availability of, social supports/networks, and factors in the built environment - and specific health outcomes, such as depression and cancer. "People engage, form relationships, and leverage resources based on how they perceive and fit into surrounding social structures, as well as economic realities," said Dr. Gehlert.
Building on these community level studies, the researchers in Chicago measured features in a four-block area around women's homes that might impede or enhance social interactions; for example, vacant buildings and lots, fences, and deteriorating infrastructure, or conversely, neighborhood watches or block clubs. "We gathered data on how people respond to these neighborhood contexts" in order to move down a level to the psychosocial, she explained. Interviewing the neighborhood women, the researchers looked for successful coping strategies.
"The connection between psychosocial factors and biological consequences makes enormous intuitive sense, despite the fact that it turns the reigning biology-centric paradigm on its head," said Dr. Gehlert. "But when you get to know the women and the stress-generating neighborhoods they live in, it's hard to maintain the belief that a biomedical approach alone is going to provide a meaningful solution to the problem of understanding health disparities."
"The CPHHD initiative highlights an increasingly sophisticated approach to the study of social context and its influence on cancer and cancer disparities," said Dr. Paige McDonald, chief of NCI's Basic and Biobehavioral Research Branch. "While preliminary, these studies are promising. However, more research is needed to understand how the macroenvironment may influence tumor biology in biologically relevant ways that contribute to differences in cancer outcomes."