Bradley E. Aouizerat

Abstract

Interindividual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify 3 subgroups of women (N = 398) with distinct persistent breast pain trajectories (ie, mild, moderate, severe) over 6 months following surgery. The purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, to examine how changes over time and in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60 to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the severe pain class reported higher scores than women in the moderate pain class. In addition, women in the moderate pain class reported higher scores than women in the mild pain class. Compared to women in the mild pain class, women in the severe pain class had significantly impaired grip strength, and women in the moderate and severe pain classes had impaired flexion and abduction.Perspective Subgroups of women with persistent postsurgical breast pain differed primarily with respect to the severity rather than the nature or underlying mechanisms of breast pain. Pervasive sensory loss and the association between persistent breast pain and sustained interference with function suggest the need for long-term clinical follow-up.

Abstract

Objective: Dopamine, iron, and inflammatory pathways are considered important to the development of restless legs syndrome (RLS). Recent genetic studies support involvement of dopamine and iron; however, cytokine gene variation in the inflammatory component remains unexplored. A recent study reported a high prevalence of RLS among HIV-infected adults. We estimate occurrence of RLS in an ethnically diverse sample of HIV-infected adults and examine differences in demographic factors, clinical characteristics, and biomarkers relating to dopamine, iron, and inflammation between adults with and without RLS symptoms. Design: A prospective longitudinal study aimed at identifying biomarkers of RLS symptom experience among HIV-infected adults. Method: 316 HIV-positive adults were evaluated using International RLS Study Group criteria. Genes were chosen for hypothesized relationships to dopamine (NOS1, NOS2), iron (HFE) or inflammation-mediated by cytokine genes (interferon [IFN], interleukin [IL], nuclear factor kappa-B [NFKB], and tumor necrosis factor alpha [TNFA]). Results: Similar to general population estimates, 11% of the sample met all four RLS diagnostic criteria. Controlling for race, gender, and hemoglobin, carrying two copies of the minor allele for IL1B rs1143643, rs1143634, or rs1143633 or carrying the minor allele for IL17A rs8193036 was associated with increased likelihood of meeting RLS diagnostic criteria. Conclusion: This study provides preliminary evidence of a genetic association between IL1B and IL17A genes and RLS.

Abstract

Background: The diagnosis of breast cancer, in combination with the anticipation of surgery, evokes fear, uncertainty, and anxiety in most women. Objective: Study purposes were to examine in patients who underwent breast cancer surgery how ratings of state anxiety changed from the time of the preoperative assessment to 6 months after surgery and to investigate whether specific demographic, clinical, symptom, and psychosocial adjustment characteristics predicted the preoperative levels of state anxiety and/or characteristics of the trajectories of state anxiety. Interventions/Methods: Patients (n = 396) were enrolled preoperatively and completed the Spielberger State Anxiety inventory monthly for 6 months. Using hierarchical linear modeling, demographic, clinical, symptom, and psychosocial adjustment characteristics were evaluated as predictors of initial levels and trajectories of state anxiety. Results: Patients experienced moderate levels of anxiety before surgery. Higher levels of depressive symptoms and uncertainty about the future, as well as lower levels of life satisfaction, less sense of control, and greater difficulty coping, predicted higher preoperative levels of state anxiety. Higher preoperative state anxiety, poorer physical health, decreased sense of control, and more feelings of isolation predicted higher state anxiety scores over time. Conclusions: Moderate levels of anxiety persist in women for 6 months after breast cancer surgery. Implications for Practice: Clinicians need to implement systematic assessments of anxiety to identify high-risk women who warrant more targeted interventions. In addition, ongoing follow-up is needed to prevent adverse postoperative outcomes and to support women to return to their preoperative levels of function.

Abstract

Subgroups of individuals may be at greater risk of cytokine-induced changes in attentional function. The purposes of this study were to identify subgroups of individuals with distinct trajectories of attentional function and evaluate for phenotypic and genotypic (i.e., cytokine gene polymorphisms) differences among these subgroups. Self-reported attentional function was evaluated in 252 participants (167 oncology patients and 85 family caregivers) using the Attentional Function Index before radiation therapy and at six additional assessments over 6 months. Three latent classes of attentional function were identified using growth mixture modeling: moderate (36.5%), moderate-to-high (48.0%), and high (15.5%) attentional function. Participants in the moderate class were significantly younger, with more comorbidities and lower functional status, than those in the other two classes. However, only functional status remained significant in multivariable models. Included in the genetic association analyses were 92 single nucleotide polymorphisms (SNPs) among 15 candidate genes. Additive, dominant, and recessive genetic models were assessed for each SNP. Controlling for functional status, only Interleukin 6 (IL6) rs1800795 remained a significant genotypic predictor of class membership in multivariable models. Each additional copy of the rare "G" allele was associated with a 4-fold increase in the odds of belonging to the lower attentional function class (95% confidence interval: [1.78, 8.92]; p = .001). Findings provide preliminary evidence of subgroups of individuals with distinct trajectories of attentional function and of a genetic association with an IL6 promoter polymorphism.

Abstract

Background: Single nucleotide polymorphisms (SNPs) in the Ryanodine receptor 3 (RYR3) gene are associated with common carotid intima media thickness (CCA cIMT) in HIV-infected men. We evaluated SNPs in the RYR3 gene among HIV-infected women participating in Women's Interagency HIV Study (WIHS). Methods: CCA cIMT was measured using B-mode ultrasound and the 838 SNPs in the RYR3 gene region were genotyped using the Illumina HumanOmni2.5-quad beadchip. The CCA cIMT genetic association was assessed using linear regression analyses among 1213 women and also separately among White (n=139), Black (n=720) and Hispanic (n=354) women after adjusting for confounders. A summary measure of pooled association was estimated using a meta-analytic approach by combining the effect estimates from the three races. Haploblocks were inferred using Gabriel's method and haplotype association analyses were conducted among the three races separately. Results: SNP rs62012610 was associated with CCA cIMT among the Hispanics (p=4.41×10-5), rs11856930 among Whites (p=5.62×10-4), and rs2572204 among Blacks (p=2.45×10-3). Meta-analysis revealed several associations of SNPs in the same direction and of similar magnitude, particularly among Blacks and Hispanics. Additionally, several haplotypes within three haploblocks containing SNPs previously related with CCA cIMT were also associated in Whites and Hispanics. Discussion: Consistent with previous research among HIV-infected men, SNPs within the RYR3 region were associated with subclinical atherosclerosis among HIV-infected women. Allelic heterogeneity observed across the three races suggests that the contribution of the RYR3 gene to CCA cIMT is complex, and warrants future studies to better understand regional SNP function.

Abstract

Background: Understanding normal volume asymmetry is essential for accurate assessment of limb volume changes following breast cancer (BC) treatment in which lymphatic function is disrupted. The purposes of this study were to evaluate for differences in dominant and nondominant limb volumes and to evaluate for interactions between the effects of dominance and side of cancer on limb volume. Methods and Results: This study evaluated preoperative limb volumes of 397 women enrolled in a prospective, longitudinal study of neuropathic pain and lymphedema. Volume was calculated from circumference. Limb resistance was measured with bioimpedance. Women were dichotomized into two groups: those whose cancer was on their dominant side and those whose cancer was on their nondominant side. Analyses of variance were used to evaluate for differences. In 47%, BC occurred on the side of the dominant limb. Except for the 30 to 40 centimeter (cm) limb volume segment, a main effect of dominance was found for all measures. The volume of the dominant limb was significantly greater than that of the nondominant limb. No main effects were found for side of cancer. A statistically significant interaction was found only at the 0 to 10cm limb volume segment. Conclusions: Prior to BC treatment, the dominant limb demonstrated lower bioimpedance resistance (-2.09%) and greater total limb volume (1.12%) than the nondominant limb. Segmental volume differences were greatest at the proximal forearm segment (2.31%) and least at the proximal arm segment (0.21%). This study provides evidence that preoperative volume assessment is important due to normal variability associated with limb dominance.

Abstract

Background and Study Objective: Telomere length provides an estimate of cellular aging and is influenced by oxidative stress and health behaviors such as diet and exercise. This article describes relationships between telomere length and sleep parameters that included total sleep time (TST), wake after sleep onset (WASO), and self-reported sleep quality in a sample of adults with chronic illness. Design and Participants: Cross-sectional study of 283 adults (74% male, 42% Caucasian) infected with human immunodeficiency virus (HIV) while living in the San Francisco Bay area, CA, USA. Ages ranged from 22-77 y. Measurements and Results: TST and WASO were estimated with wrist actigraphy across 72 h; self-reported sleep quality was assessed with the Pittsburgh Sleep Quality Index. Relative telomere length (RTL) in leukocytes was estimated by quantitative polymerase chain reaction assays. Shorter RTL was associated with older age, and RTL was shorter in males than females. RTL was unrelated to HIV disease characteristics. RTL was not associated with WASO or self-reported sleep quality. Participants with at least 7 h sleep had longer RTL than those with less than 7 h, even after controlling for the effects of age, sex, race, education, body mass index, metabolic hormones (i.e., leptin, ghrelin, adiponectin, and resistin), depression and anxiety, and sleep quality. Conclusion: Results suggest that sleep duration is associated with preserving telomere length in a population of human immunodeficiency virusinfected adults. Getting at least 7 hours of sleep at night may either protect telomeres from damage or restore them on a nightly basis.

Abstract

Depressive symptoms are common in women with breast cancer. This study evaluated how ratings of depressive symptoms changed from the time of the preoperative assessment to 6 months after surgery and investigated whether specific demographic, clinical, and symptom characteristics predicted preoperative levels of and/or characteristics of the trajectories of depressive symptoms. Characteristics that predicted higher preoperative levels of depressive symptoms included being married/partnered; receipt of adjuvant chemotherapy; more fear of metastasis; higher levels of trait anxiety, state anxiety, sleep disturbance, problems with changes in appetite; more hours per day in pain; and lower levels of attentional function. Future studies need to evaluate associations between anxiety, fears of recurrence, and uncertainty, as well as personality characteristics and depressive symptoms.

Abstract

Preoperative breast pain in women with breast cancer may result from a number of causes. Previous work from our team found that breast pain occurred in 28.2% of women (n = 398) who were about to undergo breast cancer surgery. The occurrence of preoperative breast pain was associated with a number of demographic and clinical characteristics, as well as variation in two cytokine genes. Given that ion channels regulate excitability of sensory neurons, we hypothesized that variations in potassium channel genes would be associated with preoperative breast pain in these patients. Therefore, in this study, we evaluated for associations between single-nucleotide polymorphisms and inferred haplotypes among 10 potassium channel genes and the occurrence of preoperative breast pain in patients scheduled to undergo breast cancer surgery. Multivariable logistic regression analyses were used to identify those genetic variations that were associated with the occurrence of preoperative breast pain while controlling for age and genomic estimates of and self-reported race/ethnicity. Variations in four potassium channel genes: (1) potassium voltage-gated channel, delayed rectifier, subfamily S, member 1 (KCNS1); (2) potassium inwardly rectifying channel, subfamily J, member 3 (KCNJ3); (3) KCNJ6; and (4) potassium channel, subfamily K, member 9 (KCNK9) were associated with the occurrence of breast pain. Findings from this study warrant replication in an independent sample of women who report breast pain following one or more breast biopsies.

Abstract

Purpose: To introduce current and emerging approaches that are being utilized in the field of genomics so the reader can conceptually evaluate the literature and appreciate how these approaches are advancing our understanding of health-related issues. Organizing Construct: Each approach is described and includes information related to how it is advancing research, its potential clinical utility, exemplars of current uses, challenges related to technologies used for these approaches, and when appropriate information related to understanding the evidence base for clinical utilization of each approach is provided. Web-based resources are included for the reader who would like more in-depth information and to provide opportunity to stay up to date with these approaches and their utility. Conclusions: The chosen approaches-genome sequencing, genome-wide association studies, epigenomics, and gene expression-are extremely valuable approaches for collecting research data to help us better understand the pathophysiology of a variety of health-related conditions, but they are also gaining in utility for clinical assessment and testing purposes. Clinical Relevance: Our increased understanding of the molecular underpinnings of disease will assist with better development of screening tests, diagnostic tests, tests that allow us to prognosticate, tests that allow for individualized treatments, and tests to facilitate post-treatment surveillance.