Allostatic Load—Measurement Issues in Cancer Patients and Other Populations

Introduction

An emerging hypothesis about disparities in cancer risk and outcomes among disparity populations is that psychological and social stressors impact biological processes that play a role in the initiation and progression of disease. Allostatic load is an indicator of biological dysregulation in response to psychological and social stress that is used to measure the impact of these stressors on biological functioning. AL is an index that is determined based on physiological biomarkers such as immune (C-Reactive protein), neuroendocrine (cortisol), metabolic (HbAIc), and autonomic (systolic and diastolic blood pressure) functioning also implicated in chronic diseases that are leading causes of morbidity and mortality among minority men. Several studies have examined racial differences in allostatic load, and this work has shown that individuals from disparity populations have greater allostatic load compared with those from other groups. For this reason, allostatic load has been examined as a mechanism of cancer health disparities ^{, ,} and is now being included as one of the pathways through which the social environment contributes to racial disparities in cancer risk and outcomes in emerging conceptual models of minority health and cancer health disparities. Nevertheless, important empirical questions remain about allostatic load because of inconsistencies in how this biomarker has been measured across studies and disease types and limited data about the longitudinal effects of allostatic load on disease risk and outcomes. Moreover, few efforts have been made to integrate calculation of allostatic load into clinical or public health practice; therefore, the utility of using allostatic load as a framework to improve cancer health disparities and other domains in minority health is unknown. The purpose of this chapter is to review allostatic load theory and describe key issues in measuring allostatic load in community and clinical samples. This chapter also presents findings from studies on allostatic load in cancer populations and includes a case example of how allostatic load was used as the framework to guide transdisciplinary translational research on precision medicine research within the context of cancer health disparities along with a discussion of priorities for future research on allostatic load.

Allostatic Load Theory and Conceptual Development

Allostatic load was first described by McEwen and Stellar as part of their work to describe the relationship between stress and disease risk. This work was foundational because it identified physiological systems that are activated as part of the stress response and made important distinctions between homeostasis and allostasis within the context of risk of developing chronic and acute diseases. McEwen and Stellar also introduced the concept of allostatic load as the cumulative result of physiological wear and tear across multiple systems, organs, and tissues and set the stage for future research that described the conceptual basis of this construct and investigations on the nature and distribution of allostatic load across diverse populations. According to these conceptual models, for instance, allostatic load can result when (1) there is repeated exposure to stressors, (2) adaptation to chronic stressors is reduced; (3) stress responses continue after the stressor has been alleviated; or (4) allostatic responses are not able to manage the stressor. ^,

Several aspects of allostatic load theory are relevant to minority health and cancer health disparities. First, this construct is based on the premise of physiological efforts to maintain stability when faced with challenges or stressors. The economic, social, and psychological challenges experienced by African Americans as a result of racism and discrimination are well documented, and these stressors, and the challenges that result from these sociopolitical factors, are included as precursors to physical and mental health outcomes in early conceptual models of health disparities. Further, stress exposure has been proposed as a central factor in health disparities, and allostatic load is one physical outcome included in conceptual models that are based on the stress process. In addition, many of the diseases for which there are racial disparities in risk and outcomes have been linked with stress responses (e.g., hypertension, cardiovascular disease) and are hormone dependent (e.g., breast cancer, prostate cancer). Data from animal studies have shown that exposure to social stressors (e.g., isolation) is associated with an increased likelihood of developing mammary tumors that are histologically similar to those that develop among African American women. This research has also shown that animals who had a dysregulated cortisol response in which hormonal levels do not decrease, or return to normal levels following stress exposure, are most likely to develop disease. Cortisol is the primary hormone that is responsible for the stress response; previous research has shown that African Americans have a dysregulated cortisol response because of exposure to chronic social and psychological stressors (e.g., low limited financial resources, racial discrimination). Using data from the Midlife in the US Study (MIDUS), Cohen et al. found that the typical diurnal rhythm of cortisol differs between African Americans and whites. Compared with whites, African Americans had lower cortisol levels in the morning and higher hormonal levels at the end of the day. Racial differences in cortisol were independent of SES factors, but low SES (e.g., education and income) was associated with a dysregulated cortisol response that was characterized by higher levels of cortisol during the evening among African Americans. Similar findings were reported in a recent analysis that compared diurnal cortisol slopes between African American and White men in the MIDUS II study; African American men were more likely than White men to exhibit blunted cortisol responses. In other work, Webb Hooper demonstrated that cortisol levels are lower at critical timepoints in the trajectory of a smoking cessation intervention (e.g., at baseline, end of treatment) among African Americans (vs. white). Cortisol slopes (from baseline, end of treatment, and 1-month follow-up) were also flattered among African American smokers compared with White smokers in this study. Lastly, allostatic load was higher among participants in the MIDUS II study who reported pervasive discrimination, but the association between allostatic load and discrimination was stronger among African American relative to whites.