Correlates of health-related quality of life in African Americans diagnosed with cancer: a review of survivorship studies and the Detroit research on cancer survivors cohort.

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.

Evaluation of the Immune Response within the Tumor Microenvironment in African American and Non-Hispanic White Patients with Non-Small Cell Lung Cancer.

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 based on PDL1 or tertiary lymphoid structure (TLS) status to identify differences of translational relevance.

Methods: Using a cohort of 280 patients with non-small cell lung cancer from the Inflammation, Health, Ancestry, and Lung Epidemiology study (non-Hispanic White: n = 155; African American: n = 125), we evaluated PDL1 tumor proportion score (<1% vs.

Assessing a Polygenic Risk Score for Lung Cancer Susceptibility in Non-Hispanic White and Black Populations.

Background: Polygenic risk scores (PRS) have become an increasingly popular approach to evaluate cancer susceptibility, but have not adequately represented Black populations in model development.

Methods: We used a previously published lung cancer PRS on the basis of 80 SNPs associated with lung cancer risk in the OncoArray cohort and validated in UK Biobank. The PRS was evaluated for association with lung cancer risk adjusting for age, sex, total pack-years, family history of lung cancer, history of chronic obstructive pulmonary disease, and the top five principal components for genetic ancestry.

Germline Variants in DNA Damage Repair Genes and Among Black Patients With Early-Onset Prostate Cancer.

Purpose: Genetic studies of prostate cancer susceptibility have predominantly focused on non-Hispanic White men, despite the observation that Black men are more likely to develop prostate cancer and die from the disease. Therefore, we sought to identify genetic variants in Black patients diagnosed with early-onset prostate cancer.

Methods: Whole-exome sequencing of germline DNA from a population-based cohort of Black men diagnosed with prostate cancer at age 62 years or younger was performed.

Comprehensive association analysis of speech recognition thresholds after cisplatin-based chemotherapy in survivors of adult-onset cancer.

Purpose: Deficits in speech understanding constitute one of the most severe consequences of hearing loss. Here we investigate the clinical and genetic risk factors for symmetric deterioration of speech recognition thresholds (SRT) among cancer survivors treated with cisplatin.

Methods: SRT was measured using spondaic words and calculating the mean of measurements for both ears with symmetric SRT values.

Evaluation of health behaviors and overall quality of life in younger adult African American cancer survivors.

Background: Epidemiological studies of cancer survivors have predominantly focused on non-Hispanic White, elderly patients, despite the observation that African Americans have higher rates of mortality. Therefore, we characterized cancer survivorship in younger African American survivors using the Detroit Research on Cancer Survivors (ROCS) study to assess health behaviors and quality of life.

Methods: Five hundred and seventeen patients diagnosed with any cancer between the ages of 20-49 (mean age: 42 years; SD: 6.

Pharmacogenomics of cisplatin-induced neurotoxicities: Hearing loss, tinnitus, and peripheral sensory neuropathy.

Purpose: Cisplatin is a critical component of first-line chemotherapy for several cancers, but causes peripheral sensory neuropathy, hearing loss, and tinnitus. We aimed to identify comorbidities for cisplatin-induced neurotoxicities among large numbers of similarly treated patients without the confounding effect of cranial radiotherapy.

Methods: Utilizing linear and logistic regression analyses on 1680 well-characterized cisplatin-treated testicular cancer survivors, we analyzed associations of hearing loss, tinnitus, and peripheral neuropathy with nongenetic comorbidities.

Chemotherapy-induced peripheral neuropathy in African American cancer survivors: Risk factors and quality of life outcomes.

Background: Epidemiological studies of chemotherapy-induced peripheral neuropathy (CIPN) have predominantly focused on non-Hispanic White patients, despite the observation that African Americans are more likely to experience CIPN. To address this health disparities gap, we sought to identify non-genetic risk factors and comorbidities associated with CIPN in African American cancer survivors using the Detroit Research on Cancer Survivors study.

Methods: Logistic regression was used to evaluate relationships between presence of self-reported CIPN and relevant clinical characteristics in 1045 chemotherapy-treated African American cancer survivors.

Clinical and genetic risk factors for radiation-associated ototoxicity: A report from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort.

Background: Cranial radiation therapy (CRT) is associated with ototoxicity, which manifests as hearing loss and tinnitus. The authors sought to identify clinical determinants and genetic risk factors for ototoxicity among adult survivors of pediatric cancer treated with CRT.

Methods: Logistic regression evaluated associations of tinnitus (n = 1991) and hearing loss (n = 2198) with nongenetic risk factors and comorbidities among CRT-treated survivors in the Childhood Cancer Survivor Study.

Clinical and Genome-Wide Analysis of Multiple Severe Cisplatin-Induced Neurotoxicities in Adult-Onset Cancer Survivors.

Purpose: Cisplatin is a first-line chemotherapeutic for many cancers, but causes neurotoxicity including hearing loss, tinnitus, and peripheral sensory neuropathy. However, no study has comprehensively characterized risk factors for developing multiple (>1) severe neurotoxicities.

Experimental Design: The relationship between multiple severe neurotoxicities and age, cumulative cisplatin dose, medical history, and lifestyle/behavioral factors was evaluated in 300 cisplatin-treated testicular cancer survivors using logistic regression.

Clinical and Genome-Wide Analysis of Serum Platinum Levels after Cisplatin-Based Chemotherapy.

Purpose: Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1-35 years after CBC and evaluate genetic contributions to these levels.

Experimental Design: Eligible TCS given 300 or 400 (±15) mg/m cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured.

Clinical and Genome-wide Analysis of Cisplatin-induced Tinnitus Implicates Novel Ototoxic Mechanisms.

Purpose: Cisplatin, a commonly used chemotherapeutic, results in tinnitus, the phantom perception of sound. Our purpose was to identify the clinical and genetic determinants of tinnitus among testicular cancer survivors (TCS) following cisplatin-based chemotherapy.

Experimental Design: TCS ( = 762) were dichotomized to cases (moderate/severe tinnitus; = 154) and controls (none; = 608).

Genetic and Modifiable Risk Factors Contributing to Cisplatin-induced Toxicities.

Effective administration of traditional cytotoxic chemotherapy is often limited by off-target toxicities. This clinical dilemma is epitomized by cisplatin, a platinating agent, which has potent antineoplastic activity due to its affinity for DNA and other intracellular nucleophiles. Despite its efficacy against many adult-onset and pediatric malignancies, cisplatin elicits multiple off-target toxicities that can not only severely impact a patient's quality of life but also lead to dose reductions or the selection of alternative therapies that can ultimately affect outcomes.

Gene and MicroRNA Perturbations of Cellular Response to Pemetrexed Implicate Biological Networks and Enable Imputation of Response in Lung Adenocarcinoma.

Pemetrexed is indicated for non-small cell lung carcinoma and mesothelioma, but often has limited efficacy due to drug resistance. To probe the molecular mechanisms underlying chemotherapeutic response, we performed mRNA and microRNA (miRNA) expression profiling of pemetrexed treated and untreated lymphoblastoid cell lines (LCLs) and applied a hierarchical Bayesian method. We identified genetic variation associated with gene expression in human lung tissue for the most significant differentially expressed genes (Benjamini-Hochberg [BH] adjusted p < 0.

A p53-regulated apoptotic gene signature predicts treatment response and outcome in pediatric acute lymphoblastic leukemia.

Gene signatures have been associated with outcome in pediatric acute lymphoblastic leukemia (ALL) and other malignancies. However, determining the molecular drivers of these expression changes remains challenging. In ALL blasts, the p53 tumor suppressor is the primary regulator of the apoptotic response to genotoxic chemotherapy, which is predictive of outcome.