Erin Linnenbringer

Race-Ethnicity, Poverty, Urban Stressors, and Telomere Length in a Detroit Community-based Sample

Residents of distressed urban areas suffer early aging-related disease and excess mortality. Using a community-based participatory research approach in a collaboration between social researchers and cellular biologists, we collected a unique data set of 239 black, white, or Mexican adults from a stratified, multistage probability sample of three Detroit neighborhoods. We drew venous blood and measured telomere length (TL), an indicator of stress-mediated biological aging, linking respondents’ TL to their community survey responses. We regressed TL on socioeconomic, psychosocial, neighborhood, and behavioral stressors, hypothesizing and finding an interaction between poverty and racial-ethnic group. Poor whites had shorter TL than nonpoor whites; poor and nonpoor blacks had equivalent TL; and poor Mexicans had longer TL than nonpoor Mexicans. Findings suggest unobserved heterogeneity bias is an important threat to the validity of estimates of TL differences by race-ethnicity. They point to health impacts of social identity as contingent, the products of structurally rooted biopsychosocial processes.

“I know what you told me, but this is what I think:” Perceived risk of Alzheimer disease among individuals who accurately recall their genetics-based risk estimate

Purpose: This study evaluates the Alzheimer disease risk perceptions of individuals who accurately recall their genetics-based Alzheimer disease risk assessment.Methods: Two hundred forty-six unaffected first-degree relatives of patients with Alzheimer disease were enrolled in a multisite randomized controlled trial examining the effects of communicating APOE genotype and lifetime Alzheimer disease risk information.Results: Among the 158 participants who accurately recalled their Alzheimer disease risk assessment 6 weeks after risk disclosure, 75 (47.5%) believed their Alzheimer disease risk was more than 5% points different from the Alzheimer disease risk estimate they were given. Within this subgroup, 69.3% believed that their Alzheimer disease risk was higher than what they were told (discordant high), whereas 30.7% believed that their Alzheimer disease risk was lower (discordant low). Participants with a higher baseline risk perception were more likely to have a discordant-high risk perception (P < 0.05). Participants in the discordant-low group were more likely to be APOE ε4 positive (P < 0.05) and to score higher on an Alzheimer disease controllability scale (P < 0.05).Conclusion: Our results indicate that even among individuals who accurately recall their Alzheimer disease risk assessment, many people do not take communicated risk estimates at face value. Further exploration of this clinically relevant response to risk information is warranted.

Incorporating ethnicity into genetic risk assessment for Alzheimer disease: The REVEAL study experience

Purpose: To describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants.Methods: The following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicity-specific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease.Results: Review of epidemiological data suggested notable differences in risk between African Americans and whites and that Apolipoprotein E genotype predicts risk in both groups. Discussions about the benefits and risks of stratified risk assessments reached consensus that estimates based on data from whites should not preclude enrolling African Americans, but population-specific risk curves should be created if feasible. Risk models specific to ethnicity, gender, and Apolipoprotein E genotype were subsequently developed for the randomized clinical trial that oversampled African Americans.Conclusion: The Risk Evaluation and Education for Alzheimer Disease study provides an instructive example of a process to develop risk assessment protocols that are sensitive to the implications of genetic testing for multiple ethnic groups with differing levels of risk.

Comparing test-specific distress of susceptibility versus deterministic genetic testing for Alzheimer's disease.

Genetic risk for Alzheimers disease (AD) can be conferred by the susceptibility polymorphism apolipoprotein E (APOE), where the ε4 allele increases the risk of developing late‐onset AD but is not a definitive predictor of the disease, or by autosomal dominant mutations (eg, the presenilins), which almost inevitably result in early‐onset familial AD. The purpose of this study was to compare the psychological impact of using these two different types of genetic information to disclose genetic risk for AD to family members of affected patients.

A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease.

Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimers disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD.

A randomized controlled trial of disclosing genetic risk information for Alzheimer disease via telephone

PurposeTelephone disclosure of genetic test results can improve access to services. To date, studies of its impact have focused on return of Mendelian risk information, principally hereditary cancer syndromes.MethodsIn a multisite trial of Alzheimer disease genetic risk disclosure, asymptomatic adults were randomized to receive test results in person or via telephone. Primary analyses examined patient outcomes 12 months after disclosure.ResultsData from 257 participants showed that telephone disclosure occurred 7.4 days sooner and was 30% shorter, on average, than in-person disclosure (both P < 0.001). Anxiety and depression scores were well below cutoffs for clinical concern across protocols. Comparing telephone and in-person disclosure protocols, 99% confidence intervals of mean differences were within noninferiority margins on scales assessing anxiety, depression, and test-related distress, but inconclusive about positive impact. No differences were observed on measures of recall and subjective impact. Subanalyses supported noninferiority on all outcomes among apolipoprotein E (APOE) ɛ4–negative participants. Subanalyses were inconclusive for APOE ɛ4–positive participants, although mean anxiety and depression scores were still well below cutoffs for clinical concern.ConclusionTelephone disclosure of APOE results and risk for Alzheimer disease is generally safe and helps providers meet demands for services, even when results identify an increased risk for disease.

Black-White Disparities in Breast Cancer Subtype: The Intersection of Socially Patterned Stress and Genetic Expression

Hormone receptor negative (HR-) breast cancer subtypes are etiologically distinct from the more common, less aggressive, and more treatable form of estrogen receptor positive (ER+) breast cancer. Numerous population-based studies have found that, in the United States, Black women are 2 to 3 times more likely to develop HR- breast cancer than White women. Much of the existing research on racial disparities in breast cancer subtype has focused on identifying predisposing genetic factors associated with African ancestry. This approach fails to acknowledge that racial stratification shapes a wide range of environmental and social exposures over the life course. Human stress genomics considers the role of individual stress perceptions on gene expression. Yet, the role of structurally rooted biopsychosocial processes that may be activated by the social patterning of stressors in an historically unequal society, whether perceived by individual black women or not, could also impact cellular physiology and gene expression patterns relevant to HR- breast cancer etiology. Using the weathering hypothesis as our conceptual framework, we develop a structural perspective for examining racial disparities in breast cancer subtypes, integrating important findings from the stress biology, breast cancer epidemiology, and health disparities literatures. After integrating key findings from these largely independent literatures, we develop a theoretically and empirically guided framework for assessing potential multilevel factors relevant to the development of HR- breast cancer disproportionately among Black women in the US. We hypothesize that a dynamic interplay among socially patterned psychosocial stressors, physiological & behavioral responses, and genomic pathways contribute to the increased risk of HR- breast cancer among Black women. This work provides a basis for exploring potential alternative pathways linking the lived experience of race to the risk of HR- breast cancer, and suggests new avenues for research and public health action.

Abstract A83: Development of a New Inter-Institutional Partnership to Assess Health Literacy Disparities in the Context of Kidney Cancer and Smoking

Background: Kidney cancer mortality rates are significantly higher among individuals diagnosed with later-stage disease, but there are currently no efficacious methods for kidney cancer screening. As a result, primary prevention via reduction of modifiable risk factors such as smoking, as well prompt diagnosis following early symptoms of the disease, are key to reducing kidney cancer mortality. Recent research conducted at Southern Illinois University School of Medicine (SIUSOM) has found that rural residents of Southern and Central Illinois have some of the highest kidney cancer incidence and mortality rates in the nation. However, this disparity is not fully explained by the limited number of urologists practicing within this region. Higher rates of smoking, higher thresholds for medical help-seeking behavior, and/or lower levels of health literacy may contribute to the increased incidence and mortality rates within this population, but urban-rural differences in these factors have not be examined within the region. Partnership Development: To address these critical research gaps, SIUSOM investigators with expertise in urology and clinical trial implementation developed a pilot research project with Washington University in St. Louis (WUSTL) investigators specializing in health behavior and health disparities research. The pilot project was submitted as part of an NCI-funded P20 center exploring the feasibility of building a collaborative partnership between Simmons Cancer Institute at SIUSOM and WUSTL9s Siteman Cancer Center. Research Objectives: The goals of the pilot project are to assess potential geographic differences (urban vs. rural) in: 1) health literacy and cancer literacy; 2) knowledge of smoking as a kidney cancer risk factor; and 3) degree of bother caused by general urologic symptoms. During the development and implementation of the pilot project, the research team is also monitoring the progress and barriers in building new collaborative partnerships that span two institutions located approximately 100 miles apart. Research Methods: The pilot project is currently enrolling a total of 300 individuals attending primary care or urology clinic appointments in Springfield, IL (n=60); Carbondale, IL (n=120); and St. Louis, MO (n=120). Because the pilot project is designed to assess regional variation in relevant risk factors rather than the relationship between risk factors and kidney cancer development, all clinic patients must be at least 40 years old and must not have a personal history of kidney cancer. Individuals who consent to participate in the study complete a self-administered survey via Android tablet while waiting for their clinic appointment. Interim Findings: During the pilot project development and implementation phases, we have leveraged existing institutional resources, such as the Research Electronic Data Capture (REDCap) system, to streamline our data collection and management across multiple locations. However, we have encountered some challenges in establishing uniform practices for clinic-based recruitment and enrollment, given the unique clinic organization and patient flow issues in each geographic location. Recruitment and enrollment are currently underway, and preliminary quantitative results will be available by mid-September. Citation Format: Erin Linnenbringer, Shaheen Alanee, Katina Richardson, Nirek Sharma, Aimee James, Danuta Dynda, Kevin McVary. Development of a New Inter-Institutional Partnership to Assess Health Literacy Disparities in the Context of Kidney Cancer and Smoking. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A83.

Abstract B27: Neighborhood racial concentration and hormone receptor status among California women diagnosed with breast cancer

Introduction: Recent evidence indicates that black women living in highly segregated metropolitan areas when diagnosed with breast cancer may receive their diagnosis at an earlier stage and have reduced cancer-specific and all-mortality rates if their neighborhood has a higher proportion of black residents. We conducted a cross-sectional, multilevel analysis of California Cancer Registry records merged with data from the California Neighborhoods Data System to determine whether the odds of having estrogen and progesterone negative (ER-/PR-) breast cancer are also reduced under similar neighborhood sociodemographic conditions. Methods: A total of 88,205 non-Hispanic white, non-Hispanic black, and Hispanic women, ages 18 to 108 at diagnosis with invasive breast cancer between 1996 and 2004 and lived in a census block group within a California metropolitan statistical area (MSA) were included in the analysis. Block groups were used as the neighborhood-level unit of analysis. Racial residential segregation was assessed at the MSA level and was operationalized using the multigroup entropy index, a measure of “evenness,” or the degree to which all racial groups present in an MSA are evenly distributed across its component parts (i.e., census tracts). Results: Controlling for block group socioeconomic status and individual sociodemographic and tumor characteristics, higher percent of black residents in a neighborhood significantly reduced the odds of having ER-/PR- breast cancer relative to having ER+/PR+ cancer among black women (-3.7% for every 10% increase in black neighborhood residents; p = 0.01). When the analysis was further stratified by multigroup entropy scores, black women residing in highly segregated MSA9s had a similar reduction in ER-/PR- risk (-3.8% for every 10% increase in black neighborhood residents; p = 0.02), but the reduction was only marginally significant in less segregated MSA9s (-4.1% for every 10% increase in black neighborhood residents; p = 0.10). There was a modest increase in the risk of ER-/PR- subtype among Hispanics not accounting for segregation(+4.6% for every 10% increase in black neighborhood residents; p = 0.053), and among Hispanics living in less segregated MSA9s (+7.0% for every 10% increase in black neighborhood residents; p = 0.074), but not among Hispanics living in more segregated metropolitan areas. No associations between neighborhood black composition and ER-/PR- subtype were observed among whites. The neighborhood concentration of Hispanic residents generated a different pattern of ER-/PR- risk. Among Hispanic women, greater percentages of Hispanic neighborhood residents increased the odds of having ER-/PR- versus ER+/PR+ breast cancer (+2.7% for every 10% increase in Hispanic neighborhood residents, p Conclusions: The racial/ethnic composition of neighborhoods is associated with the risk of ER-/PR- subtype among Californian women diagnosed with breast cancer. This relationship differs across racial/ethnic groups, and to a lesser extent, by the degree of race-based residential segregation across the broader metropolitan area. Citation Format: Erin Linnenbringer, Scarlett Lin Gomez. Neighborhood racial concentration and hormone receptor status among California women diagnosed with breast cancer. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B27. doi:10.1158/1538-7755.DISP13-B27

P-004: Incorporating ethnicity into genetic risk assessment for Alzheimer’s disease: The reveal study experience

patients [average age 72 (range 61-90, SD 6), average education 11 years (range 4-20 years, SD 2.7)] who were randomly recruited from Grady Health Systems Medical clinics. Subjects were given the Folstein Mini Mental State Exam, Draw a Clock task, four item Memory Impairment Screen and Time and Change Task. Results: 186 patients were able to complete the MMSE, with an average completion time of 6.6 minutes (range 2.7-19.3 SD 2.5). The higher the z score, indicating better performance, the less time it took to complete the MMSE (r -.50, p .001). Impaired patients took significantly longer (mean 480.2 seconds, SE 19.8) than intact patients (mean 345.2 seconds, SE 10.5). Using norms from Crum et al., 63 patients (33.9%) scored in the impaired range. Thirty-six patients took longer than eight minutes to complete the MMSE. Of these, 24 (67%) scored impaired, and 12 (33%) scored non-impaired. Of the 12 non-impaired patients, four additional patients were impaired on the Clock Drawing Test, indicating that 78% of patients who took longer than eight minutes were impaired on one of the two screens. Conclusion: Results suggest that an eight minute time limit on the MMSE may be effective in identifying African Americans with mild cognitive impairment or other forms of dementia who are in need of more detailed evaluation and treatment.