Andrew D. Frugé

Associations between Obesity, Body Fat Distribution, Weight Loss and Weight Cycling on Serum Pesticide Concentrations

OBJECTIVE Preliminary studies suggest pesticides may be linked to increased cancer risk. Since most pesticides are lipophilic and stored within adipose tissue, serum levels of organochlorines are affected not only by environmental exposures, but also by factors related to lipid turnover and storage. Our objective was to investigate whether serum organochlorines are influenced by weight loss, body fat distribution, and weight cycling. METHODS Ten overweight women were recruited upon entry into a weight loss program and surveyed regarding weight history, childbearing/lactation, and exposure to environmental contaminants. Anthropometric measures and phlebotomy were conducted at baseline and at four weeks (mean weight loss=5.1 kg). Serum was analyzed for 19 common polychlorinated pesticides and metabolites and 10 PCB congeners. RESULTS Organochlorine levels were not significantly affected by weight loss nor associated with body mass index (BMI). Strong positive correlations were noted between levels of DDE/DDT and age (DDE β=0.6986/p=0.0246/DDT β=0.6536/p=0.0404) and between DDE/DDT and waist-to-hip ratio (WHR) (DDE β=0.4356/p=0.0447/DDT β=0.8108/p=0.0044). Trends were noted for decreased levels of DDT in women who reported more episodes of weight cycling. CONCLUSION Serum organochlorine levels may be affected not only by age, but also factors related to lipid turnover (i.e., episodes of weight cycling and WHR), and warrants further study.

Detailed methods of two home-based vegetable gardening intervention trials to improve diet, physical activity, and quality of life in two different populations of cancer survivors

BACKGROUND Cancer survivors suffer from long-term adverse effects that reduce health-related quality of life (QOL) and physical functioning, creating an urgent need to develop effective, durable, and disseminable interventions. Harvest for Health, a home-based vegetable gardening intervention, holds promise for these domains. METHODS This report describes the methods and recruitment experiences from two randomized controlled feasibility trials that employ a waitlist-controlled design. Delivered in partnership with Cooperative Extension Master Gardeners, this intervention provides one-on-one mentorship of cancer survivors in planning and maintaining three seasonal vegetable gardens over 12months. The primary aim is to determine intervention feasibility and acceptability; secondary aims are to explore effects on objective and subjective measures of diet, physical activity and function, and QOL and examine participant factors associated with potential effects. One trial is conducted exclusively among 82 female breast cancer survivors residing in the Birmingham, AL metropolitan area (BBCS); another broadly throughout Alabama among 46 older cancer survivors aged >60 (ASCS). RESULTS Response rates were 32.6% (BBCS) and 52.3% (ASCS). Both trials exceeded 80% of their accrual target. Leading reasons for ineligibility were removal of >10 lymph nodes (lymphedema risk factor), lack of physician approval, and unwillingness to be randomized to the waitlist. CONCLUSION To date, recruitment and implementation of Harvest for Health appears feasible. DISCUSSION Although both studies encountered recruitment challenges, lessons learned can inform future larger-scale studies. Vegetable gardening interventions are of interest to cancer survivors and may provide opportunities to gain life skills leading to improvements in overall health and QOL.

Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer

Background:Obesity is associated with aggressive prostate cancer. To explore whether weight loss favourably affects tumour biology and other outcomes, we undertook a presurgical trial among overweight and obese men with prostate cancer.Methods:This single-blinded, two-arm randomised controlled trial explored outcomes of a presurgical weight loss intervention (WLI) that promoted ∼1 kg per week loss via caloric restriction and increased physical activity (PA). Forty overweight/obese men with clinically confirmed prostate cancer were randomised to the WLI presurgery or to a control arm; changes in weight, body composition, quality-of-life, circulating biomarkers, gene expression, and immunohistochemical markers in tumour and benign prostatic tissue were evaluated.Results:The study period averaged 50 days. Mean (s.d.) change scores for the WLI vs control arms were as follows: weight: −4.7 (3.1) kg vs −2.2 (4.4) kg (P=0.0508); caloric intake: −500 (636) vs −159 (600) kcal per day (P=0.0034); PA: +0.9 (3.1) vs +1.7 (4.6) MET-hours per day (NS); vitality: +5.3 (7.l4) vs −1.8 (8.1) (P=0.0491); testosterone: +55.1 (86.0) vs −48.3 (203.7) ng dl−1 (P=0.0418); sex hormone-binding globulin: +14.0 (14.6) vs +1.8 (7.6) nmol l−1 (P=0.0023); and leptin: −2.16 (2.6) vs −0.03 (3.75) (P=0.0355). Follow-up Ki67 was significantly higher in WLI vs control arms; median (interquartile range): 5.0 (2.5,10.0) vs 0.0 (0.0,2.5) (P=0.0061) and several genes were upregulated, for example, CTSL, GSK3B, MED12, and LAMC2.Conclusions:Intentional weight loss shows mixed effects on circulating biomarkers, tumour gene expression, and proliferative markers. More study is needed before recommending weight loss, in particular rapid weight loss, among men with prostate cancer.

Dietary Changes Impact the Gut Microbe Composition in Overweight and Obese Men with Prostate Cancer Undergoing Radical Prostatectomy

BACKGROUND Diet and obesity influence prostate cancer risk and progression-effects that may be mediated through the gut microbiome. OBJECTIVE Our aim was to explore relationships among diet, gut microbes, and Gleason sum in overweight and obese prostate cancer patients enrolled in a presurgical weight-loss trial. DESIGN Randomized controlled trial (NCT01886677) secondary analysis. PARTICIPANTS/SETTING In 2013-2014, 40 prostate cancer patients in the southeastern United States were randomized and allocated equally to weight-loss and wait-list control arms while they awaited prostatectomy; stool samples were collected on a subset of 22 patients. INTERVENTION Registered dietitian nutritionists and exercise physiologists provided semi-weekly in-person and telephone-based guidance on calorie-restricted diets and exercise to promote an approximate weight loss of 0.91 kg/wk. MAIN OUTCOME MEASURES Baseline and follow-up 24-hour dietary recalls were conducted and analyzed (using the Automated Self-Administered 24-hour dietary recall system; National Cancer Institute, Bethesda, MD) for macronutrients, micronutrients, and food groups. Microbiome analysis targeting the V4 region of the 16S ribosomal RNA gene was performed on fecal samples. Biopsy Gleason sum data were accessed from diagnostic pathology reports. STATISTICAL ANALYSES PERFORMED Associations between dietary factors and operational taxonomic units were determined by β-diversity analysis. Wilcoxon signed rank, and Mann-Whitney U testing assessed within- and between-arm differences. Associations between Gleason sum and operational taxonomic units, and diet and operational taxonomic units, were analyzed using Spearman correlations. RESULTS At baseline, Proteobacteria (median 0.06, interquartile range 0.01 to 0.16) were abundant, with four orders positively associated with Gleason sum. Gleason sum was associated with Clostridium (ρ=.579; P=0.005) and Blautia (ρ=-0.425, P=0.049). Increased red meat consumption from baseline was associated with Prevotella (ρ=-.497; P=0.018) and Blautia (ρ=.422; P=0.039). Men who increased poultry intake had decreased Clostridiales abundance (P=0.009). CONCLUSIONS This hypothesis-generating study provides a starting point for investigating the relationships between the fecal microbiome, diet, and prostate cancer. Adequately powered studies are required to further explore and validate these findings.

Exploring effects of presurgical weight loss among women with stage 0–II breast cancer: protocol for a randomised controlled feasibility trial

Introduction Obesity is a known risk factor for postmenopausal breast cancer and is associated with poorer prognosis for premenopausal and postmenopausal patients; however, the aetiological mechanisms are unknown. Preclinical studies support weight loss via caloric restriction and increased physical activity as a possible cancer control strategy, though few clinical studies have been conducted. We undertook a feasibility trial among women recently diagnosed with stage 0–II breast cancer hypothesising that presurgical weight loss would be feasible, safe and result in favourable changes in tumour markers and circulating biomarkers. Methods and analysis A two-arm randomised controlled trial among 40 overweight or obese women, newly diagnosed with stage 0–II breast cancer and scheduled for surgery was planned. The attention control arm received upper body progressive resistance training and diet counselling to correct deficiencies in nutrient intake; the experimental arm received the same plus counselling on caloric restriction and aerobic exercise to achieve a weight loss of 0.68–0.919 kg/week. In addition to achieving feasibility benchmarks (accruing and retaining at least 80% of participants, and observing no serious adverse effects attributable to the intervention), we will explore the potential impact of an acute state of negative energy balance on tumour proliferation rates (Ki-67), as well as other tumour markers, serum biomarkers, gene expression, microbiome profiles and other clinical outcomes (eg, quality of life). Outcomes for the 2 study arms are compared using mixed models repeated-measures analyses. Ethics and dissemination Ethics approval was received from the University of Alabama at Birmingham Institutional Review Board (Protocol number F130325009). Study findings will be disseminated through peer-reviewed publications. Given that this is one of the first studies to investigate the impact of negative energy balance directly on tumour biology in humans, larger trials will be pursued if results are favourable. Trial registration number NCT02224807; Pre-results.

Fingernail and toenail clippings as a non-invasive measure of chronic cortisol levels in adult cancer survivors

PurposeCancer survivors are at greater risk of comorbidities and functional decline due to physiological and psychological stress which can be measured by salivary cortisol. If saliva is used, multiple samples must be collected to accurately quantify long-term stress; however, fingernail (FN) and toenail (TN) clippings offer an opportunity to measure retrospective cortisol levels in a non-invasive manner.MethodsThree sets of FN and TN clippings were collected at 12-month intervals in conjunction with saliva samples from cancer survivors (n = 109) participating in two clinical trials. FN and TN samples were stored at room temperature (RT); a subset underwent additional processing and freezing before analysis. Cortisol levels were determined via enzyme immunoassay, and correlation coefficients were generated to determine overall correspondence of the individual measures.ResultsMatched RT and frozen samples were highly correlated for TN (r = 0.950, p = 5.44 × 10−37) and FN (r = 0.784, p = 1.05 × 10−10). Correlations between RT FN and TN were statistically significant (r = 0.621, p = 3.61 × 10− 17), as were frozen FN and TN (r = 0.310, p = 0.0283). RT, but not frozen TN and FN correlated with salivary cortisol (r = 0.580, p = 1.65 × 10− 16 and r = 0.287, p = 0.00042 for TN and FN, respectively).ConclusionsFN and TN cortisol levels correlate with salivary cortisol in adult cancer survivors and may offer a less invasive and convenient means for measuring chronic cortisol levels.

Head and Neck Cancer Adherence to Dietary Recommendations using Theory-Based Tools: Future Research Directions

Head and Neck Cancer Adherence to Dietary Recommendations using Theory-Based Tools: Future Research Directions The possibility of applying social cognitive theory (SCT) as a potential framework in improving head and neck cancer (HNCa) patient adherence to dietary interventions as reported by Rogers et al. is very interesting. The very high internal reliability of the SCT scales related to diet adherence was impressive.This is the first study to examine predictors or correlates of diet adherence in HNCa patients based on a behavioral change theory. Further, this study supports the need and legitimacy of the use of SCT in assessing dietary adherence to recommendations by HNCa patients.

Physiological Effort in Submaximal Fitness Tests Predicts Weight Loss in Overweight and Obese Men with Prostate Cancer in a Weight Loss Trial

Background Obesity and weight gain after the diagnosis of prostate cancer are associated with an increased risk of prostate cancer recurrence and mortality; individualized plans to help prostate cancer survivors maintain or lose weight may be beneficial for recurrence risk reduction. Herein, we explore whether gains in cardiovascular fitness predict successful weight loss in men participating in a weight loss trial (NCT01886677). Methods Forty men were randomized to receive twice-weekly in-person and telephone-based guidance on calorie-restricted diets and aerobic exercise to promote ~0.91 kg/week weight loss, or wait-list control. Thirty-two men completed submaximal VO2 Treadmill Tests (TT), anthropometric measures and two 24-hour dietary recalls at baseline and follow-up. For this secondary analysis, study arms were combined and associations between baseline and longitudinal changes in physiological effort (PE, measured by heart rate during TT), predicted VO2max, caloric intake and weight loss were analyzed. Results Men lost 3.4 kg in 50 ± 23 days on the study. Multivariate linear regression indicated weight change was associated with change in PE at stage 2TT (Partial R = 0.635, p < 0.001), days on study (Partial R = −0.589, p = 0.002) and change in caloric intake (Partial R = 0.457, p = 0.019). Conclusions Untrained men experiencing elevated heart rates during stage 2TT at baseline were able to achieve greater weight loss over the study period; this association was strengthened by a decrease in PE at the same level from baseline to follow-up concomitant with reduced caloric intake. Therefore, for these middle-aged and older men with lower aerobic fitness, exercise appears to be a key factor in achieving higher degrees of weight loss.

Characteristics of cancer patients participating in presurgical lifestyle intervention trials exploring effects on tumor biology

Background Poor diet and insufficient physical activity are strongly associated with an increased risk of several cancers. Preclinical studies suggest that lifestyle modifications may exert favorable effects on tumor biology. Randomized controlled trials in the presurgical setting serve as an ideal means to translate this research to humans; however, little is known about the characteristics of patients who enroll in these presurgical trials versus those who do not. Methods Screening databases from three presurgical lifestyle intervention trials for breast and prostate cancer patients conducted at Duke University Medical Center (NCT00049309) and the University of Alabama at Birmingham (NCT02224807 and NCT01886677) were combined for analysis. Demographic and anthropometric differences between enrolled vs. non-enrolled individuals were assessed using Chi-square for categorical variables and t-tests for continuous variables. Results There was no difference in participation rate when comparing minority status or overweight and obese patients. However, obese females were slightly more likely to enroll than women who were overweight (p = 0.110), a trend not seen in men. Women were also less likely than men to participate if their study site was >25 miles from their home (p = 0.034). Patients who had completed a college degree were somewhat less likely to enroll than those with less educational attainment (p = 0.072). Of those who did not enroll, 80% cited a lack of time. Conclusion Similar to other clinical trials, lack of time is a leading barrier to enrollment, and travel/distance appears to be a greater barrier for women in presurgical studies. Larger presurgical lifestyle intervention trials will require tailored strategies to enhance recruitment.