Disparities in Breast Cancer Mortality: The Influence of Social Environment on Gene Expression

Background and Purpose: Black and white disparities in mortality from cancer have increased through time. Although white women are more likely than black women to get breast cancer, black women are 37% more likely to die from it. The National Cancer Institute estimates that 40% of the black/white breast cancer disparity can be accounted for by differential access to care. That leaves 60% unaccounted for. The vast majority of breast cancers are not due to hereditary mutations of breast cancer genes. Instead, 70% to 80% of breast cancers are due to sporadic mutations that occur throughout the life cycle. Taking a holistic approach to cancer incidence and mortality, the current study attempts to predict the occurrence of non-hereditary (sporadic) mutations of breast cancer genes based on factors at the neighborhood and community level (e.g. crime, collective efficacy) and psychosocial response to those factors. Methods: We report results from the Chicago arm of our multi-national study of gene and environment interactions in breast cancer. 230 African-American women newly diagnosed with their first occurrence of breast cancer were enrolled in the study from three Chicago hospitals that serve a range of socioeconomic and insurance statuses (e.g., no insurance, Medicaid, private insurance). Tumors are collected at the time of surgery and analyzed for evidence of sporadic mutations. Data on community, neighborhood, and psychosocial factors are gathered, beginning four to six weeks pst-surgery, in three ways: (1) women are interviewed in their homes on three occasions, six months apart, for 18 hours of face-to-face interviews, on topics including health history, living arrangements, social network, perceptions of social support, stress, and discrimination. Women complete daily diaries and collect salivary cortisol specimens four times per day over three days every six months to assess disrupted stress hormone response as a means in which factors in the social environment “get under the skin” to change breast cancer genes; (2) investigators map the built (physical) environment over the four blocks around women's homes to evaluate features that either impede or enhance social interactions. They measure traffic and developed a measure of the safety of each four-block area, based on vacant lots and buildings, etc.; and, (3) publicly-available data on crime, safety of housing, SES, collective efficacy, etc. are geo-coded to women's addresses. A number of analyses, including HLM, were used to test a model about neighborhood and community influences on gene functioning through psychosocial responses. Results: Neighborhood violent crime and frequent moves were associated with felt loneliness among women. A two-factor “psychological suite” (loneliness and depression and feelings of anomie) linked neighborhood factors to disrupted stress hormone response, which in turn was linked to sporadic mutations. Conclusions and Implications: The sporadic mutations that make up 70 to 80% of breast cancers can be predicted by neighborhood and community characteristics that impact psychosocial functioning, disrupt stress hormone response, and turn off the body's natural ability to repair sporadic mutations of breast cancer genes. This suggests interventions at multiple levels, such as risk profiles that combine individual and group factors.