Claire Jungyoun Han

Breast Cancer Risk in Relation to Ambient Air Pollution Exposure at Residences in the Sister Study Cohort

Background: Some but not all past studies reported associations between components of air pollution and breast cancer, namely fine particulate matter ≤2.5 μm (PM2.5) and nitrogen dioxide (NO2). It is yet unclear whether risks differ according to estrogen receptor (ER) and progesterone receptor (PR) status. Methods: This analysis includes 47,591 women from the Sister Study cohort enrolled from August 2003 to July 2009, in whom 1,749 invasive breast cancer cases arose from enrollment to January 2013. Using Cox proportional hazards and polytomous logistic regression, we estimated breast cancer risk associated with residential exposure to NO2, PM2.5, and PM10. Results: Although breast cancer risk overall was not associated with PM2.5 [HR = 1.03; 95% confidence intervals (CI), 0.96–1.11], PM10 (HR = 0.99; 95% CI, 0.98–1.00), or NO2 (HR = 1.02; 95% CI, 0.97–1.07), the association with NO2 differed according to ER/PR subtype (P = 0.04). For an interquartile range (IQR) difference of 5.8 parts per billion (ppb) in NO2, the relative risk (RR) of ER+/PR+ breast cancer was 1.10 (95% CI, 1.02–1.19), while there was no evidence of association with ER−/PR− (RR = 0.92; 95% CI, 0.77–1.09; Pinteraction = 0.04). Conclusions: Within the Sister Study cohort, we found no significant associations between air pollution and breast cancer risk overall. But we observed an increased risk of ER+/PR+ breast cancer associated with NO2. Impact: Though these results suggest there is no substantial increased risk for breast cancer overall in relation to air pollution, NO2, a marker of traffic-related air pollution, may differentially affect ER+/PR+ breast cancer. Cancer Epidemiol Biomarkers Prev; 24(12); 1907–9. ©2015 AACR.

Serum Tryptophan Metabolite Levels During Sleep in Patients With and Without Irritable Bowel Syndrome (IBS)

Poor sleep and stress are more frequently reported by women with irritable bowel syndrome (IBS) than by healthy control (HC) women. The pathophysiology linking poor sleep and stress to gastrointestinal symptoms remains poorly understood. We used a metabolomic approach to determine whether tryptophan (TRP) metabolites differ between women with and without IBS and whether the levels are associated with sleep indices and serum cortisol levels. This study sample included 38 women with IBS and 21 HCs. The women were studied in a sleep laboratory for three consecutive nights. On the third night of the study, a social stressor was introduced, then blood samples were drawn every 20 min and sleep indices were measured. Metabolites were determined by targeted liquid chromatography tandem mass spectrometry in a sample collected 1 hr after the onset of sleep. The ratios of each metabolite to TRP were used for analyses. Correlations were controlled for age and oral contraceptive use. Melatonin/TRP levels were lower (p = .005) in the IBS-diarrhea group versus the IBS-constipation and HC groups, and kynurenine/TRP ratios tended to be lower (p = .067) in the total IBS and IBS-diarrhea groups compared to HCs. Associations within the HC group included melatonin/TRP with polysomnography-sleep efficiency (r = .61, p = .006) and weaker positive correlations with the other ratios for either sleep efficiency or percentage time in rapid eye movement sleep (r > .40, p = .025–.091). This study suggests that reductions in early nighttime melatonin/TRP levels may be related to altered sleep quality in IBS, particularly those with diarrhea.

COMT Val158Met Polymorphism and Symptom Improvement Following a Cognitively Focused Intervention for Irritable Bowel Syndrome

Background Our nurse-delivered comprehensive self-management (CSM) program, a cognitive behavioral therapy intervention, is effective in reducing gastrointestinal and psychological distress symptoms in patients with irritable bowel syndrome (IBS). Findings from non-IBS studies indicate that the catechol-O-methyltransferase (COMT) Val158Met polymorphism may moderate the efficacy of cognitive behavioral therapy. It is unknown whether this COMT polymorphism is associated with symptom improvements in patients with IBS. Objective We tested whether this COMT Val158Met polymorphism influences the efficacy of our 2-month CSM intervention. Methods We analyzed data from two published randomized controlled trials of CSM. The combined European American sample included 149 women and 23 men with IBS (CSM, n = 111; usual care [UC], n = 61). The primary outcomes were daily reports of abdominal pain, depression, anxiety, and feeling stressed measured 3 and 6 months after randomization. Secondary outcomes were additional daily symptoms, retrospective psychological distress, IBS quality of life, and cognitive beliefs about IBS. The interaction between COMT Val158Met polymorphism and treatment group (CSM vs. UC) in a generalized estimating equation model tested the main objective. Results At 3 months, participants with at least one Val allele benefited more from CSM than did those with the Met/Met genotype (p = .01 for anxiety and feeling stressed, and p < .16 for abdominal pain and depression). The moderating effect of genotype was weaker at 6 months. Discussion Persons with at least one Val allele may benefit more from CSM than those homozygous for the Met allele. Future studies with larger and more racially diverse samples are needed to confirm these findings. RCT Registration Parent studies were registered at ClinicalTrials.gov (NCT00167635 and NCT00907790).

Relationships of abdominal pain, reports to visceral and temperature pain sensitivity, conditioned pain modulation, and heart rate variability in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a heterogeneous condition with a number of pathophysiological mechanisms that appear to contribute to symptom chronicity. One of these is altered pain sensitivity.

Investigation of a Lifestyle Intervention in Women at High Risk of Breast Cancer

One fourth of breast cancer can be attributed to sedentary lifestyles and being overweight or obese. This pilot study was conducted to explore whether a 6-month lifestyle intervention affected body composition and obesity-related biomarkers among women at high risk of breast cancer. Overweight/obese women at high risk of breast cancer were randomized to the control group or to the intervention. The intervention was an individually tailored, cognitive-behavioral therapy program that assists women in identifying strategies to improve their nutrition and physical activity habits with the goal of reduced adiposity. We compared changes in body composition and plasma biomarkers from baseline to 6 months. Body weight, adiposity, leptin, insulin resistance, and C-reactive protein were significantly reduced in the intervention group versus controls. No significant differences were observed in adiponectin, insulin, glucose, or interleukin-6. Our findings suggest that this intervention improves the metabolic and inflammatory profiles of overweight/obese women at risk of breast cancer.

Stool and urine trefoil factor 3 levels: associations with symptoms, intestinal permeability, and microbial diversity in irritable bowel syndrome

Previously we showed that urine trefoil factor 3 (TFF3) levels were higher in females with irritable bowel syndrome (IBS) compared to non-IBS females. To assess if TFF3 is associated with symptoms and/or reflect alterations in gastrointestinal permeability and gut microbiota in an IBS population, we correlated stool and urine TFF3 levels with IBS symptoms, intestinal permeability, stool microbial diversity and relative abundance of predominant bacterial families and genera. We also tested the relationship of stool TFF3 to urine TFF3, and compared results based on hormone contraception use. Samples were obtained from 93 females meeting Rome III IBS criteria and completing 4-week symptom diaries. TFF3 levels were measured by ELISA. Permeability was assessed with the urine lactulose/mannitol (L/M) ratio. Stool microbiota was assessed using 16S rRNA. Stool TFF3, but not urine TFF3, was associated positively with diarrhoea and loose stool consistency. Higher stool TFF3 was also associated with lower L/M ratio and microbial diversity. Of the 20 most abundant bacterial families Mogibacteriaceae and Christensenellaceae were inversely related to stool TFF3, with only Christensenellaceae remaining significant after multiple comparison adjustment. There were no significant relationships between stool or urine TFF3 levels and other symptoms, nor between stool and urine levels. In premenopausal females, urine TFF3 levels were higher in those reporting hormone contraception. Collectively these results suggest that higher stool TFF3 levels are associated with IBS symptoms (loose/diarrhoeal stools), lower gut permeability, and altered stool bacteria composition (decreased diversity and decreased Christensenellaceae), which further suggests that TFF3 may be an important marker of host-bacteria interaction.

A Concept Analysis of Personalized Health Care in Nursing

Purpose The purpose of the study is to identify the concept of personalized health care in nursing and to address future direction in person-centered nursing care. Background Personalized health care has attracted increased attention in the twenty-first century. As more and more preclinical studies are focusing on cost-effective and patient-centered care, there also has been an identified need for a personalized health care in nursing. Yet the term lacks clear definition and interests among healthcare professionals. Review Methods Rodgers’ strategy for concept analysis was used in this analysis. A literature review for 1960–2014 was conducted for the following keywords: nursing care, personalized, and health care. Results The analysis demonstrates that personalized health care in nursing is an intangible asset, including explicit attributes (interprofessional collaboration and individualized care approach) and implicit attributes (managing personal vulnerabilities: molecular-based health information and self-health-seeking behaviors). The result of this analysis provides a guide for further conceptual and empirical research and clinical practice in the personalized healthcare era. Conclusion This concept analysis represents an effort to describe the attributes of a concept regarded as representing an important feature of nursing care and to promote discourse that will enhance maturation of the concept into one that is established with clearly delineated characteristics.

Abstract A34: Impact of a lifestyle intervention on metabolic pathways: Results from the Diet, Exercise, Emotional Processing, and Mindfulness (DEEM) intervention

Abstracts: AACR Special Conference: Metabolism and Cancer; June 7-10, 2015; Bellevue, WA Background: Breast cancer is the most common non-dermatologic malignancy in women. One-fifth of breast cancers can be attributed to sedentary lifestyles and overweight/obesity. More than two-thirds of U.S. women are overweight or obese. Excess body weight and body fat may affect breast cancer risk through a number of mechanisms, including metabolic pathways (i.e., adipokines, inflammation, and insulin) and estrogen metabolism. To date, limited research has investigated the impact of lifestyle interventions on metabolic changes among women at high risk for breast cancer. The purpose of this pilot study was to test the feasibility of the 6-month exercise and diet intervention and to explore the impact of lifestyle intervention versus control on metabolic changes. Methods: Participants were recruited through the Seattle Cancer Care Alliance. Sixteen women were randomized with half assigned to the control group. Eligible women were 35-65 years of age, had a body mass index (BMI) between 28-40, and were at high risk of breast cancer. Dual-energy X-ray Absorptiometry (DEXA) scans, questionnaire data, blood and urine samples were collected at baseline, 3, 6, and 9- months. The DEEM lifestyle intervention is an individually-tailored intervention that includes motivational enhancement therapy, cognitive and behavioral skills training, and psychological education. Group counseling sessions were conducted weekly for 3 months then tapered over next 3 months. We measured the changes in weight, percent adiposity, central waist/hip circumferences, plasma biomarkers (adiponectin, leptin, C-reactive protein [CRP], Interleukin-6 [IL-6], Homeostatic Model Assessment-Insulin Resistance [HOMA-IR]), and urinary estrogen metabolites (Estrogen DNA Adduct [EDA]). Results: Results showed an average weight loss of 4.1 kg (- 4.6 %) in intervention group versus controls (weight gain 1.4 kg, +1.6 %) at 6 months ( p = 0.02). Intervention participants experienced a decrease in percent mean adiposity (-3 %) and waist circumference (-0.2 inches) but no change in hip circumference; controls had increases in all 3 measures (+1.5 %, +0.7 inches, +2.9 inches). These changes were not significantly different. Self-reported physical activity differed between intervention and control participants (6.8 versus.1.4 hrs. /wk., p = 0.01). On average vegetable, fruit, protein intake increased and carbohydrate intake decreased only in intervention group, but not significantly different from controls. Women in the intervention arm reduced plasma CRP (mg/dL) from 0.39 to 0.26 (- 0.13 [34.5 %]) versus from 0.45 to 0.63 (+ 0.18 [39 %]) in controls ( p = 0.06); and reduced plasma leptin (ng/ml) from 18.1 to 14.7 (-3.4 [18 %]) versus from 21.8 to 21.9 (+0.1 [0.1 %]) in controls ( p = 0.10). Twenty-five percent of the intervention participants went from insulin resistant to non-insulin resistant (HOMA-IR< 2.0), while none of the controls reduced their HOMA-IR. No significant differences were observed in adiponectin, IL-6 and EDA. Conclusion: In this pilot study, the DEEM intervention facilitated weight loss and reduced adiposity. Our findings also suggest that a lifestyle intervention can improve the metabolic health of overweight/obese women at high risk of breast cancer. Future work is needed to confirm this finding in a large-scale study. Citation Format: Claire Jungyoun Han, Larissa Korde, Scott Reding, Kerryn Reding. Impact of a lifestyle intervention on metabolic pathways: Results from the Diet, Exercise, Emotional Processing, and Mindfulness (DEEM) intervention. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A34.

Fatigue Measures in Noncancer Gastrointestinal Disorders: A Critical Review.

Fatigue is commonly reported by patients with noncancer gastrointestinal (GI) disorders such as organic and functional GI disorders. This critical review was conducted to evaluate fatigue measures that have been used in these patients. A systematic search using six databases (PubMed, PsycINFO, EMBASE, CINAHL, ProQuest, and Cochrane Review) was conducted from January 2000 to June 2014, and evaluations and reviews of fatigue instruments were performed by two independent reviewers (author and medical librarian). Fourteen instruments from 25 studies were identified. Ten instruments were solely focused on fatigue and four were multisymptom instruments. The average quality score of the 14 instruments was 10.7 (range, 6–14) out of 14. There were five instruments with high overall scores based on usability/feasibility, clinical/research utility, and psychometric properties (3 fatigue-specific and 2 multisymptom). There are valid and reliable measures that are currently available to assess fatigue in noncancer GI patients. Utilization of these common measures may assist clinicians (GI healthcare providers) and researchers to better understand the impact of fatigue in these patients. The instruments with low-quality scores cannot be chosen for routine use without further validation.