Bradley E. Aouizerat

Abstract

Persistent pain following breast cancer surgery is a significant clinical problem. Although immune mechanisms may play a role in the development and maintenance of persistent pain, few studies have evaluated for associations between persistent breast pain following breast cancer surgery and variations in cytokine genes. In this study, associations between previously identified extreme persistent breast pain phenotypes (ie, no pain vs severe pain) and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes were evaluated. In unadjusted analyses, the frequency of 13 SNPs and 3 haplotypes in 7 genes differed significantly between the no pain and severe pain classes. After adjustment for preoperative breast pain and the severity of average postoperative pain, 1 SNP (ie, interleukin [IL] 1 receptor 2 rs11674595) and 1 haplotype (ie, IL10 haplotype A8) were associated with pain group membership. These findings suggest a role for cytokine gene polymorphisms in the development of persistent breast pain following breast cancer surgery. Perspective This study evaluated for associations between cytokine gene variations and the severity of persistent breast pain in women following breast cancer surgery. Variations in 2 cytokine genes were associated with severe breast pain. The results suggest that cytokines play a role in the development of persistent postsurgical pain.

Abstract

Oncology patients are at high risk for developing sleep disturbance and fatigue due a number of physiological and psychological factors associated with cancer, its treatment, and the burden of living with a chronic condition. Progress in our understanding of sleep disturbance and fatigue in oncology patients has been stymied by varying definitions for each symptom, as well as different instruments to measure each symptom. In addition, the co-occurrence of these and other common symptoms suggests that analytic methodologies that are currently available should be considered to model the relationships between these and among other common symptoms. The purpose of the chapter is to describe the prevalence, risk factors, measurement considerations, proposed mechanisms for and novel approaches to the study of these two common symptoms in oncology patients. Interventions to improve sleep and reduce fatigue are also described.

Abstract

Background: Lymphedema (LE) is a frequent complication following breast cancer treatment. While progress is being made in the identification of phenotypic risk factors for the development of LE, little information is available on the molecular characterization of LE. The purpose of this study was to determine if variations in pro-and anti-inflammatory cytokine genes were associated with LE following breast cancer treatment. Methods and Results: Breast cancer patients completed a number of self-report questionnaires. LE was evaluated using bioimpedance spectroscopy. Genotyping was done using a custom genotyping array. No differences were found between patients with (n=155) and without LE (n=387) for the majority of the demographic and clinical characteristics. Patients with LE had a significantly higher body mass index, more advanced disease, and a higher number of lymph nodes removed. Genetic associations were identified for three genes (i.e., interleukin (IL4) 4 (rs2227284), IL 10 (rs1518111), and nuclear kappa factor beta 2 (NFKB2 (rs1056890)) associated with inflammatory responses. Conclusions: These genetic associations suggest a role for a number of pro-and anti-inflammatory genes in the development of LE following breast cancer treatment.

Abstract

Purpose: This study explored the relationships between variations in cytokines genes and depressive symptoms in a sample of patients who were assessed prior to and for six months following breast cancer surgery. Phenotypic differences between Resilient (n = 155) and Subsyndromal (n = 180) depressive symptom classes, as well as variations in cytokine genes were evaluated. Method: Patients were recruited prior to surgery and followed for six months. Growth mixture modeling was used to identify distinct latent classes based on Center for Epidemiological Studies Depression (CES-D) Scale scores. Eighty-two single nucleotide polymorphisms and 35 haplotypes among 15 candidate cytokine genes were evaluated. Results: Patients in the Subsyndromal class were significantly younger, more likely to be married or partnered, and reported a significantly lower functional status. Variation in three cytokine genes (i.e., interferon gamma receptor 1 (IFNGR1 rs9376268), interleukin 6 (IL6 rs2069840), tumor necrosis factor alpha (TNFA rs1799964)), as well as age and functional status predicted membership in the Subsyndromal versus the Resilient class. Conclusions: A variation in TNFA that was associated with Subsyndromal depressive symptoms in a sample of patients and their family caregivers was confirmed in this sample. Variations in cytokine genes may place these patients at higher risk for the development of Subsyndromal levels of depressive symptoms.

Abstract

Fatigue has been associated with inflammation and cytokine activity among adults, but this relationship has not been evaluated among adults living with HIV. Diurnal patterns of fatigue have been previously identified in adults with HIV/AIDS. Thus, the purpose of this study was to describe these fatigue patterns in relation to cytokine plasma concentrations and gene polymorphisms. A convenience sample of 317 adults living with HIV/AIDS completed a measure of fatigue in the morning and evening for three consecutive days; participants reporting low levels of both morning and evening fatigue (n= 110) or high levels of fatigue in the morning and evening (n= 114) were included in the analysis, resulting in a final sample of 224 adults (151 men, 55 women, and 18 transgender). Plasma cytokines were analyzed, and genotyping was conducted for 15 candidate genes involved in cytokine signaling: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL), nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB-1 and -2), and tumor necrosis factor alpha (TNFA). Demographic and clinical variables were evaluated as potential covariates. Controlling for genomic estimates of ancestry and self-reported race/ethnicity and gender, the high fatigue pattern was associated with five single nucleotide polymorphisms (SNPs): IL1B rs1071676 and rs1143627, IL4 rs2243274, and TNFA rs1800683 and rs1041981. The IL1B and TNFA polymorphisms were not associated with plasma levels of IL-1β or TNFα, respectively. This study strengthens the evidence for an association between inflammation and fatigue. In this chronic illness population, the cytokine polymorphisms associated with high levels of morning and evening fatigue provide direction for future personalized medicine intervention research.

Abstract

Study Objectives: Cytokine activity and polymorphisms have been associated with sleep outcomes in prior animal and human research. The purpose of this study was to determine whether circulating plasma cytokines and cytokine polymorphisms are associated with the poor sleep maintenance commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Design: Cross-sectional descriptive study. Setting: HIV clinics and community sites in the San Francisco Bay area. Participants: A convenience sample of 289 adults (193 men, 73 women, and 23 transgender) living with HIV/AIDS. Interventions: None. Measurements and Results: A wrist actigraph was worn for 72 h to estimate the percentage of wake after sleep onset (WASO%) and total sleep time (TST), plasma cytokines were analyzed, and genotyping was conducted for 15 candidate genes involved in cytokine signaling: interferongamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL1B, IL1R2, IL1R2, IL2, IL4, IL6, IL8, IL10, IL13, IL17A), nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB1 and NFKB2), and tumor necrosis factor-alpha (TNFA). Controlling for demographic variables such as race and sex, and clinical variables such as CD4+ count and medications, higher WASO% was associated with single nucleotide polymorphisms (SNPs) of IL1R2 rs11674595 and TNFA rs1041981 and less WASO% was associated with IL2 rs2069776. IL1R2 rs11674595 and TNFA rs1041981 were also associated with short sleep duration. Conclusions: This study strengthens the evidence for an association between inflammation and sleep maintenance problems. In this chronic illness population, cytokine polymorphisms associated with wake after sleep onset provide direction for intervention research aimed at comparing anti-inflammatory mechanisms with hypnotic agents for improving sleep maintenance and total sleep time.

Abstract

Context The relatively low number of older patients in cancer trials limits knowledge of how older adults experience symptoms associated with cancer and its treatment. Objectives This study evaluated for differences in the symptom experience across four older age groups (60-64, 65-69, 70-74, 75 years). Methods Demographic, clinical, and symptom data from 330 patients aged >60 years who participated in one Australian and two U.S. studies were evaluated. The Memorial Symptom Assessment Scale was used to evaluate the occurrence, severity, frequency, and distress of 32 symptoms commonly associated with cancer and its treatment. Results On average, regardless of the age group, patients reported 10 concurrent symptoms. The most prevalent symptoms were physical in nature. Worrying was the most common psychological symptom. For 28 (87.5%) of the 32 Memorial Symptom Assessment Scale symptoms, no age-related differences were found in symptom occurrence rates. For symptom severity ratings, an age-related trend was found for difficulty swallowing. As age increased, severity of difficulty swallowing decreased. For symptom frequency, age-related trends were found for feeling irritable and diarrhea, with both decreasing in frequency as age increased. For symptom distress, age-related trends were found for lack of energy, shortness of breath, feeling bloated, and difficulty swallowing. As age increased, these symptoms received lower average distress ratings. Conclusion Additional research is warranted to examine how age differences in symptom experience are influenced by treatment differences, aging-related changes in biological or psychological processes, or age-related response shift.

Abstract

BACKGROUND A large amount of interindividual variability exists in the occurrence of symptoms in patients receiving chemotherapy (CTX). The purposes of the current study, which was performed in a sample of 582 oncology outpatients who were receiving CTX, were to identify subgroups of patients based on their distinct experiences with 25 commonly occurring symptoms and to identify demographic and clinical characteristics associated with subgroup membership. In addition, differences in quality of life outcomes were evaluated. METHODS Oncology outpatients with breast, gastrointestinal, gynecological, or lung cancer completed the Memorial Symptom Assessment Scale before their next cycle of CTX. Latent class analysis was used to identify subgroups of patients with distinct symptom experiences. RESULTS Three distinct subgroups of patients were identified (ie, 36.1% in Low class; 50.0% in Moderate class, and 13.9% in All High class). Patients in the All High class were significantly younger and more likely to be female and nonwhite, and had lower levels of social support, lower socioeconomic status, poorer functional status, and a higher level of comorbidity. CONCLUSIONS Findings from the current study support the clinical observation that some oncology patients experience a differentially higher symptom burden during CTX. These high-risk patients experience significant decrements in quality of life.

Abstract

Purpose/Objectives: To identify latent classes of individuals with distinct quality-of-life (QOL) trajectories, to evaluate for differences in demographic characteristics between the latent classes, and to evaluate for variations in pro- and anti-inflammatory cytokine genes between the latent classes. Design: Descriptive, longitudinal study. Setting: Two radiation therapy departments located in a comprehensive cancer center and a community-based oncology program in northern California. Sample: 168 outpatients with prostate, breast, brain, or lung cancer and 85 of their family caregivers (FCs). Methods: Growth mixture modeling (GMM) was employed to identify latent classes of individuals based on QOL scores measured prior to, during, and for four months following completion of radiation therapy. Single nucleotide polymorphisms (SNPs) and haplotypes in 16 candidate cytokine genes were tested between the latent classes. Logistic regression was used to evaluate the relationships among genotypic and phenotypic characteristics and QOL GMM group membership. Main Research Variables: QOL latent class membership and variations in cytokine genes. Findings: Two latent QOL classes were found: higher and lower. Patients and FCs who were younger, identified with an ethnic minority group, had poorer functional status, or had children living at home were more likely to belong to the lower QOL class. After controlling for significant covariates, between-group differences were found in SNPs in interleukin 1 receptor 2 (IL1R2) and nuclear factor kappa beta 2 (NFKB2). For IL1R2, carrying one or two doses of the rare C allele was associated with decreased odds of belonging to the lower QOL class. For NFKB2, carriers with two doses of the rare G allele were more likely to belong to the lower QOL class. Conclusions: Unique genetic markers in cytokine genes may partially explain interindividual variability in QOL. Implications for Nursing: Determination of high-risk characteristics and unique genetic markers would allow for earlier identification of patients with cancer and FCs at higher risk for poorer QOL. Knowledge of these risk factors could assist in the development of more targeted clinical or supportive care interventions for those identified.

Abstract

Purpose: In this prospective, longitudinal study, we extend our findings on persistent breast pain in patients (n=398) following breast cancer surgery and evaluate the prevalence and characteristics of persistent pain in the arm/shoulder. In addition, differences in the severity of common symptoms and quality of life outcomes measured prior to surgery, among the arm pain classes, were evaluated. Methods and sample: Patients were recruited from Breast Care Centers located in a Comprehensive Cancer Center, two public hospitals, and four community practices. Patients were assessed prior to and monthly for six months following breast cancer surgery. Results: Using growth mixture modeling, patients were classified into no (41.6%), mild (23.6%), and moderate (34.8%) arm pain classes based on ratings of worst arm/shoulder pain. Compared to the no pain class, patients in the moderate pain class were significantly younger, had a higher body mass index, and were more likely to report preoperative breast pain and swelling in the affected breast. In addition, patients in the moderate pain class reported higher levels of depression, anxiety, and sleep disturbance than the no pain class. Conclusions: Findings suggest that approximately 35% of women experience persistent levels of moderate arm/shoulder pain in the first six months following breast cancer surgery. Moderate arm/shoulder pain is associated with clinically meaningful decrements in functional status and quality of life.