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Advances in cancer screening and treatment have improved survival after a diagnosis of cancer. As the number of cancer survivors as well as their overall life-expectancy increases, investigations of health-related quality of life (HRQOL) are critical in understanding the factors that promote the optimal experience over the course of survivorship. However, there is a dearth of information on determinants of HRQOL for African American cancer survivors as the vast majority of cohorts have been conducted predominantly among non-Hispanic Whites. In this review, we provide a review of the literature related to HRQOL in cancer survivors including those in African Americans. We then present a summary of published work from the Detroit Research on Cancer Survivors (ROCS) cohort, a population-based cohort of more than 5000 African American cancer survivors. Overall, Detroit ROCS has markedly advanced our understanding of the unique factors contributing to poorer HRQOL among African Americans with cancer. This work and future studies will help inform potential interventions to improve the long-term health of this patient population.
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BACKGROUND: African Americans have higher incidence and mortality from lung cancer than non-Hispanic Whites, but investigations into differences in immune response have been minimal. Therefore, we compared components of the tumor microenvironment among African Americans and non-Hispanic Whites diagnosed with non-small cell lung cancer (NSCLC) based on PD-L1 or tertiary lymphoid structure (TLS) status to identify differences of translational relevance. METHODS: Using a cohort of 280 NSCLC patients from the INHALE study (non-Hispanic White: n=155; African American: n=125), we evaluated PD-L1 tumor proportion score (<1% vs. ≥1%) and TLS status (presence/absence), comparing differences within the tumor microenvironment based on immune cell distribution and differential expression of genes. RESULTS: Tumors from African Americans had a higher proportion of plasma cell signatures within the tumor microenvironment than non-Hispanic Whites. In addition, gene expression patterns in African American PD-L1 positive samples suggest these tumors contained greater numbers of γδ T-cells and resting dendritic cells, along with fewer CD8+ T-cells after adjusting for age, sex, pack-years, stage, and histology. Investigation of differential expression of B-cell/plasma cell related genes between the two patient populations revealed that two immunoglobulin genes (IGKV2-29 and IGLL5) were associated with decreased mortality risk in African Americans. CONCLUSIONS: In the first known race-stratified analysis of tumor microenvironment components in lung cancer based on PD-L1 expression or TLS status, differences within the immune cell composition and transcriptomic signature were identified that may have therapeutic implications. IMPACT: Future investigation of racial variation within the tumor microenvironment may help direct the use of immunotherapy.
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BACKGROUND: Immune checkpoint inhibitors (ICI) have profoundly impacted survival among patients with metastatic non-small cell lung cancer (NSCLC). However, population-based studies evaluating this impact on survival by race and socioeconomic factors are lacking. METHODS: We utilized the SEER-Medicare database to identify patients with metastatic NSCLC diagnosed between 2015 and 2019. The primary study outcomes were the receipt of an ICI and overall survival (OS). Chi-square tests and logistic regression were utilized to identify demographic factors associated with receipt of ICI. The Kaplan-Meier method was used to calculate 2-year OS rates, and log-rank tests were used to compared survival by race/ethnicity. RESULTS: Out of 17,134 patients, approximately 39% received an ICI. Those diagnosed with cancer recently (in 2019), who are relatively younger (<85 years old), non-Hispanic white, non-Hispanic Asian, or Hispanic, living in high socioeconomic status or metropolitan areas, not Medicaid eligible, and with adenocarcinoma histology were more likely to receive ICI. The 2-year OS rate from diagnosis was 21% for the overall population. The 2-year OS rate from ICI initiation was 30%, among those who received at least one cycle and 11% among those who did not receive ICI. The 2-year OS rates were higher among non-Hispanic whites (22%) and non-Hispanic Asians (23%) compared to non-Hispanic Blacks (15%) and Hispanics (17%). There was no significant racial differences in survival for those who received ICI. CONCLUSION: ICI utilization rates and the resulting outcomes were inferior for certain vulnerable groups, mandating the need for strategies to improve access to care.
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PURPOSE: Sleep disturbances represent a modifiable target to improve quality of life and longer-term outcomes in cancer survivors. However, the association between sleep health and overall quality of life in African American cancer survivors has been poorly assessed, a population at increased risk for morbidity and mortality. METHODS: Seven hundred and eighteen Detroit Research on Cancer Survivors (ROCS) cohort participants completed a supplemental sleep survey at the time of enrollment, which included the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Insomnia Severity Index (ISI). Linear and logistic regression was used to evaluate the association between sleep and mental health, while block regression models were used to estimate the contribution of clustered factors to Health-Related Quality of Life (HRQOL). RESULTS: Nearly 60% of the cohort reported symptoms indicative of poor sleep quality on the PSQI, 15% reported excessive daytime sleepiness on the ESS, and 12% reported moderate to severe insomnia on the ISI. Survivors with elevated ISI scores reported FACT-G scores that were 17 points lower than those without symptoms of insomnia (95% CI: - 13.1, - 21.2). Poor sleep health accounted for the largest proportion of variability in FACT-G scores (R2 = 0.27) and change in R2 value (0.18) when compared to comorbidities, health behaviors, cancer-related factors, and demographics. CONCLUSIONS: Overall sleep health was significantly associated with poorer HRQOL and variability in FACT-G scores. Additional studies investigating a causal relationship between sleep and HRQOL are needed to determine whether sleep quality could affect disparities in cancer outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Addressing sleep quality in cancer survivors may improve long-term health and HRQOL.
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BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. RESULTS: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior. CONCLUSIONS: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. IMPACT: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.
Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Fumadores , Estudio de Asociación del Genoma Completo , Proyectos de Investigación , Fumar/efectos adversosRESUMEN
BACKGROUND: Social risks are common among cancer survivors who have the fewest financial resources; however, little is known about how prevalence differs by age at diagnosis, despite younger survivors' relatively low incomes and wealth. METHODS: The authors used data from 3703 participants in the Detroit Research on Cancer Survivors (ROCS) cohort of Black cancer survivors. Participants self-reported several forms of social risks, including food insecurity, housing instability, utility shut-offs, not getting care because of cost or lack of transportation, and feeling unsafe in their home neighborhood. Modified Poisson models were used to estimate prevalence ratios and 95% confidence intervals (CIs) of social risks by age at diagnosis, controlling for demographic, socioeconomic, and cancer-related factors. RESULTS: Overall, 35% of participants reported at least one social risk, and 17% reported two or more risks. Social risk prevalence was highest among young adults aged 20-39 years (47%) followed by those aged 40-54 years (43%), 55-64 years (38%), and 65 years and older (24%; p for trend < .001). Compared with survivors who were aged 65 years and older at diagnosis, adjusted prevalence ratios for any social risk were 1.75 (95% CI, 1.42-2.16) for survivors aged 20-39 years, 1.76 (95% CI, 1.52-2.03) for survivors aged 40-54 years, and 1.41 (95% CI, 1.23-1.60) for survivors aged 55-64 years at diagnosis. Similar associations were observed for individual social risks and experiencing two or more risks. CONCLUSIONS: In this population of Black cancer survivors, social risks were inversely associated with age at diagnosis. Diagnosis in young adulthood and middle age should be considered a risk factor for social risks and should be prioritized in work to reduce the financial effects of cancer on financially vulnerable cancer survivors.