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1.  Long-term Outcomes of the FRESH START Trial: Exploring the Role of Self-efficacy in Cancer Survivors’ Maintenance of Dietary Practices and Physical Activity 
Psycho-oncology  2012;22(4):876-885.
Objective
This study examined whether changes in self-efficacy explain the effects of a mailed print intervention on long-term dietary practices of breast and prostate cancer survivors. The relationship between change in self-efficacy and long-term physical activity (PA) also was examined.
Methods
Breast and prostate cancer survivors (N=543) from 39 U.S. states and two Canadian provinces participated in the FRESH START intervention trial. Participants were randomly assigned to receive a 10-month program of mailed print materials on diet and PA available in the public domain or a 10-month program of tailored materials designed to increase fruit and vegetable (F&V) intake, decrease fat intake, and/or increase PA. Changes in self-efficacy for F&V intake and fat restriction were analyzed as potential mediators of the intervention’s effects on diet at 2-year follow-up. Because we previously found that change in self-efficacy for PA did not vary by group assignment, the relationship between change in self-efficacy and PA at 2-year follow-up was examined across study conditions.
Results
Results suggest that change in self-efficacy for fat restriction partially explained the intervention’s effect on fat intake (mean indirect effect=-.28), and change in self-efficacy for F&V consumption partially explained the intervention’s effect on daily F&V intake (mean indirect effect=.11). Change in self-efficacy for fat restriction partially accounted for the intervention’s impact on overall diet quality among men only (mean indirect effect=.60). Finally, change in self-efficacy for PA predicted PA at 2-year follow-up.
Conclusions
Findings suggest that self-efficacy may influence long-term maintenance of healthy lifestyle practices among cancer survivors.
doi:10.1002/pon.3089
PMCID: PMC3429767  PMID: 22544562
cancer; oncology; survivors; diet; physical activity; randomized controlled trial
2.  Flaxseed-Derived Enterolactone Is Inversely Associated with Tumor Cell Proliferation in Men with Localized Prostate Cancer 
Journal of Medicinal Food  2013;16(4):357-360.
Abstract
Enterolactone and enterodiol, mammalian lignans derived from dietary sources such as flaxseed, sesame seeds, kale, broccoli, and apricots, may impede tumor proliferation by inhibiting activation of nuclear factor kappa B (NFκB) and vascular endothelial growth factor (VEGF). We examined the associations between urinary enterolactone and enterodiol with prostatic tumor expression of NFκB, VEGF, and Ki67 among 147 patients with prostate cancer who participated in a presurgical trial of flaxseed supplementation (30 g/day) for ∼30 days. Urinary enterolignans and tissue biomarkers were determined by high-performance liquid chromatography and immunohistochemistry, respectively. After supplementation, we observed significant correlations between intakes of plant lignan and urinary concentrations of total enterolignans (ρ=0.677, P<.0001), enterolactone (ρ=0.676, P<.0001), and enterodiol (ρ=0.628, P<.0001). Importantly, we observed that total urinary enterolignans and enterolactone were significantly and inversely correlated with Ki67 in the tumor tissue (ρ=−0.217, P=.011, and ρ=−0.230, P=.007, respectively), and a near-significant inverse association was observed for enterodiol (ρ=−0.159, P=.064). An inverse association was observed between enterolactone and VEGF (ρ=−0.143, P=.141), although this did not reach statistical significance. We did not observe an association between enterolignans and NFκB. In conclusion, flaxseed-derived enterolignans may hinder cancer cell proliferation via VEGF-associated pathways.
doi:10.1089/jmf.2012.0159
PMCID: PMC3624628  PMID: 23566060
diet; flaxseed; lignans; phytoestrogens; prostatic neoplasia
3.  Carbohydrate Restriction, Prostate Cancer Growth, and the Insulin-Like Growth Factor Axis 
The Prostate  2008;68(1):11-19.
BACKGROUND
Recent evidence suggests carbohydrate intake may influence prostate cancer biology. We tested whether a no-carbohydrate ketogenic diet (NCKD) would delay prostate cancer growth relative to Western and low-fat diets in a xenograft model.
METHODS
Seventy-five male SCID mice were fed a NCKD (84% fat–0% carbohydrate–16% protein kcal), low-fat (12% fat–72% carbohydrate–16% protein kcal), or Western diet (40% fat–44% carbohydrate–16% protein kcal). Low-fat mice were fed ad libitum and the other arms fed via a modified-paired feeding protocol. After 24 days, all mice were injected with LAPC-4 cells and sacrificed when tumors approached 1,000 mm3.
RESULTS
Despite consuming equal calories, NCKD-fed mice lost weight (up to 15% body weight) relative to low-fat and Western diet-fed mice and required additional kcal to equalize body weight. Fifty-one days after injection, NCKD mice tumor volumes were 33% smaller than Western mice (rank-sum, P = 0.009). There were no differences in tumor volume between low-fat and NCKD mice. Dietary treatment was significantly associated with survival (log-rank, P = 0.006), with the longest survival among the NCKD mice, followed by the low-fat mice. Serum IGFBP-3 was highest and IGF-1:IGFBP-3 ratio was lowest among NCKD mice while serum insulin and IGF-1 levels were highest in Western mice. NCKD mice had significantly decreased hepatic fatty infiltration relative to the other arms.
CONCLUSIONS
In this xenograft model, despite consuming more calories, NCKD-fed mice had significantly reduced tumor growth and prolonged survival relative to Western mice and was associated with favorable changes in serum insulin and IGF axis hormones relative to low-fat or Western diet.
doi:10.1002/pros.20683
PMCID: PMC3959866  PMID: 17999389
prostatic neoplasms; diet; carbohydrate; fat; ketogenesis; insulin; IGF-1
4.  Obesity is associated with higher 4E-BP1 expression in endometrial cancer 
Current biomarker findings  2014;2014(4):1-7.
Purpose
Obesity is associated with risk and prognosis of endometrial cancer (EC), and the mammalian target of rapamycin complex 1 (mTORC1) pathway may play an instrumental role. We sought to explore the associations between cellular proliferation, Akt, and 4E binding protein-1 (4E-BP1) (a downstream target of mTORC1), in obese and nonobese women with and without EC.
Methods
Archival tissue-specimens from endometrial biopsies were grouped into two broad categories based on the observed disease behavior and similarities in tissue staining patterns: benign/hyperplasia (without cytologic atypia) (n=18) versus atypia (complex hyperplasia with cytologic atypia)/carcinoma (n=25). The characteristics of the study population, including height and weight to determine body mass index (BMI: kg/m2), were abstracted from medical records. Immunohistochemistry was used to assess the phosphorylated (p)Akt, p4E-BP1, and antigen Ki67.
Results
Cytoplasmic and nuclear pAkt were significantly associated with cytoplasmic p4E-BP1 (ρ=+0.48, ρ=+0.50) (P<0.05) and nuclear p4E-BP1 (ρ=+0.40, ρ=+0.44) (P<0.05); cytoplasmic and nuclear p4E-BP1 were significantly associated with Ki67 (ρ=+0.46, ρ=+0.59) (P<0.05). Compared with the benign/hyperplasia group, the women with atypia/carcinoma had significantly higher cytoplasmic and nuclear p4E-BP1 and Ki67. This staining pattern was similar in obese women; however, in nonobese women, neither cytoplasmic nor nuclear p4E-BP1staining differed between benign/hyperplasia versus atypia/carcinoma.
Conclusion
The activation of 4E-BP1 was higher in the obese women with EC. Adiposity may be a key factor to consider in future studies investigating the role of 4E-BP1 as a biomarker and therapeutic target in EC.
doi:10.2147/CBF.S53530
PMCID: PMC3955094  PMID: 24639918
mTORC1; immunohistochemistry; gynecologic malignancy; corpus uterine; BMI; biomarker
5.  Reducing Breast Cancer Recurrence with Weight Loss, a Vanguard Trial: The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial 
Contemporary clinical trials  2012;34(2):282-295.
Breast cancer is the most common invasive cancer among women in developed countries. Obesity is a major risk factor for breast cancer recurrence and mortality in both pre-and postmenopausal women. Co-morbid medical conditions are common among breast cancer survivors. The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) study is a 4-year randomized clinical trial of 693 overweight/obese women aged ≥21 years diagnosed with any early stage breast cancer (stages I[≥1 cm]-III) within the previous five years, designed to demonstrate the feasibility of achieving sustained weight loss and to examine the impact of weight loss on quality of life and co-morbidities, and to enable future exploration of biochemical mechanisms linking obesity to lower likelihood of disease-free survival. This trial is strategically designed as a vanguard for a fully-powered trial of women who will be evaluated for breast cancer recurrence and disease-free survival. Participants were recruited between 2010 and 2012 at four sites, had completed initial therapies, and had a body mass index between 25 and 45 kg/m2. The intervention featured a group-based cognitive-behavioral weight loss program with telephone counseling and tailored newsletters to support initial weight loss and subsequent maintenance, with the goal of 7% weight loss at two years. This study has high potential to have a major impact on clinical management and outcomes after a breast cancer diagnosis. This trial initiates the effort to establish weight loss support for overweight or obese breast cancer survivors as a new standard of clinical care.
doi:10.1016/j.cct.2012.12.003
PMCID: PMC3593786  PMID: 23266440
Obesity; Weight Reduction; Breast Cancer; Quality of Life; Co-Morbidities
6.  Differences in Baseline Characteristics and Outcomes at One-and Two-Year Follow-up of Cancer Survivors Accrued via Self-Referral versus Cancer Registry in the FRESH START Diet and Exercise Trial 
Participant accrual to research studies is a challenge, and oftentimes advertisements are used to supplement cases ascertained through clinic caseloads and cancer registries. It is unknown however, if cases ascertained through these two sources differ. In this study, we compare self-referred (n=209) versus cancer registry-ascertained participants (n=334) enrolled in FRESH START, a randomized controlled trial promoting a healthy diet and increased exercise among breast and prostate cancer survivors. The two groups were compared on baseline characteristics, adherence, attrition, and outcomes by study arm. Compared to participants enrolled from registries, self-referrals were significantly younger (54.1±10.4 vs. 58.7±10.7 years), more likely to have later-staged disease and to have received chemotherapy (40% vs. 19%), and more likely to report “fighting spirit” coping styles (50% vs. 30%), lower quality-of-life (88.2+15.1 vs. 92.0+12.9), fewer co-morbid conditions (1.87±1.60 vs. 2.24±1.78), and lower consumption of 5 or more daily servings of fruits and vegetables (35% vs. 45%)(p-values <.05). While no differences in behavior change were observed between self-referred and registry-ascertained cases assigned to the tailored intervention arm, this was not the case within the attention control arm. Among those who received the attention control intervention of standardized materials in the public domain, self-referred versus registry-ascertained participants demonstrated significantly greater increases in exercise at 1-year follow-up, and significantly greater increases in fruit and vegetable consumption at both 1- and 2-year follow-up (p-values <.05). Several differences exist between self-referred versus registry-ascertained participants, including motivation to respond to standardized educational materials which appears significantly greater in self-referred populations.
doi:10.1158/1055-9965.EPI-07-0705
PMCID: PMC3842166  PMID: 18483353
patient selection; registries; neoplasms; advertising
7.  Developing an intervention to address physical activity barriers for African–American women in the deep south (USA) 
Women's health (London, England)  2013;9(3):10.2217/whe.13.20.
Aim
To address high rates of inactivity and related chronic diseases among African–American women.
Materials & methods
Eleven focus groups on physical activity barriers for African–American women in the deep south (USA) were conducted (n = 56). Feedback guided an intervention development process. The resulting Home-Based Individually Tailored Physical Activity Print intervention was vetted with the target population in a 1-month, single arm, pre–post test demonstration trial (n = 10).
Results
Retention was high (90%). Intent-to-treat analyses indicated increases in motivational readiness for physical activity (70% of sample) and physical activity (7-day Physical Activity Recall) from baseline (mean: 89.5 min/week, standard deviation: 61.17) to 1 month (mean: 155 min/week, standard deviation: 100.86). Small improvements in fitness (6-Min Walk Test), weight and psychosocial process measures were also found.
Conclusion
Preliminary findings show promise and call for future randomized controlled trials with larger samples to determine efficacy. Such low-cost, high-reach approaches to promoting physical activity have great potential for addressing health disparities and benefiting public health.
doi:10.2217/whe.13.20
PMCID: PMC3816507  PMID: 23638785
African–merican women; exercise; health disparity; physical activity
8.  Obesity, Energy Balance and Cancer: New Opportunities for Prevention 
Obesity is associated with increased risk and poor prognosis for many types of cancer. The mechanisms underlying the obesity-cancer link are becoming increasingly clear and provide multiple opportunities for primary to tertiary prevention. Several obesity-related host factors can influence tumor initiation, progression and/or response to therapy, and these have been implicated as key contributors to the complex effects of obesity on cancer incidence and outcomes. These host factors include insulin, insulin-like growth factor-1, leptin, adiponectin, steroid hormones, cytokines, and inflammation-related molecules. Each of these host factors is considered in the context of energy balance and as potential targets for cancer prevention. The possibility of prevention at the systems level, including energy restriction, dietary composition and exercise is considered as is the importance of the newly-emerging field of stem cell research as a model for studying energy balance and cancer prevention.
doi:10.1158/1940-6207.CAPR-12-0140
PMCID: PMC3641761  PMID: 23034147
neoplasms; obesity; diet; growth factors; hormones
9.  Weight Management and its Role in Breast Cancer Rehabilitation 
Cancer  2012;118(8 0):10.1002/cncr.27466.
Overweight and obesity are risk factors for post-menopausal breast cancer, and many women diagnosed with breast cancer, irrespective of menopausal status, gain weight after diagnosis. Weight management plays an important role in rehabilitation and recovery since obesity and/or weight gain may lead to poorer breast cancer prognosis, as well as prevalent co-morbid conditions (e.g. cardiovascular disease and diabetes), poorer surgical outcomes (e.g., increased operating and recovery times, higher infection rates, and poorer healing), lymphedema, fatigue, functional decline, and poorer health and overall quality of life. Health care professionals should encourage weight management at all phases of the cancer care continuum as a means to potentially avoid adverse sequelae and late effects, as well as to improve overall health and possibly survival. Comprehensive approaches that involve dietary and behavior modification, and increased aerobic and strength training exercise have shown promise in either preventing weight gain or promoting weight loss, reducing biomarkers associated with inflammation and comorbidity, and improving lifestyle behaviors, functional status, and quality of life in this high-risk patient population.
doi:10.1002/cncr.27466
PMCID: PMC3812811  PMID: 22488702
Breast neoplasms; obesity; weight loss; diet; exercise
10.  LONG-TERM PHYSICAL ACTIVITY OUTCOMES OF HOME-BASED LIFESTYLE INTERVENTIONS AMONG BREAST AND PROSTATE CANCER SURVIVORS 
Purpose
Few studies have investigated long-term effects of physical activity (PA) interventions. The goal of this study was to evaluate whether or not increased levels of moderate to vigorous physical activity (MVPA) were maintained by cancer survivors one-year after receipt of two home-based interventions.
Methods
The FRESH START trial randomized 543 breast and prostate cancer survivors to 1-of-2 mailed print diet and exercise interventions: sequentially-tailored vs. standardized (attention control). Each arm received eight mailings over a 1-year period, with follow-up at 1- and 2-years. This analysis focuses solely on the 400 participants who had suboptimal levels of MVPA at baseline (measured by the 7-Day Physical Activity Recall) and who completed the 2-year study.
Results
Median minutes of MVPA at baseline, 1-year and 2-year follow-up in the tailored intervention arm were as follows: 0, 90, and 60 mins/wk, respectively. The corresponding values in the attention-control group were 0, 30, and 30 mins/wk. Significant improvements in MVPA from baseline to 2-year follow-up were observed in both study arms (p < 0.01). While significant between-arm differences were observed at 1-year follow-up (p < 0.01), by 2-year follow-up there was only the suggestion of a trend (p = 0.08).
Conclusions
This study provides evidence that mailed-print exercise interventions result in significant and sustainable improvements in MVPA among newly-diagnosed cancer survivors that are observed well after the intervention is complete. While tailored interventions, as compared to standardized materials, appear to produce superior improvements in MVPA initially, these differences diminish over time.
doi:10.1007/s00520-011-1370-y
PMCID: PMC3641190  PMID: 22249915
breast neoplasms; prostatic neoplasms; maintenance; physical activity; intervention; durability; exercise
11.  The Effects of Varying Dietary Carbohydrate and Fat Content on Survival in a Murine LNCaP Prostate Cancer Xenograft Model 
Purpose
Numerous dietary factors elevate serum levels of insulin and insulin-like growth factor I (IGF-I), both potent prostate cancer mitogens. We tested whether varying dietary carbohydrate and fat, without energy restriction relative to comparison diets, would slow tumor growth and reduce serum insulin, IGF-I, and other molecular mediators of prostate cancer in a xenograft model.
Experimental Design
Individually caged male severe combined immunodeficient mice (n = 130) were randomly assigned to one of three diets (described as percent total calories): very high-fat/no-carbohydrate ketogenic diet (NCKD: 83% fat, 0% carbohydrate, 17% protein), low-fat/high-carbohydrate diet (LFD: 12% fat, 71% carbohydrate, 17% protein), or high-fat/moderate-carbohydrate diet (MCD: 40% fat, 43% carbohydrate, 17% protein). Mice were fed to maintain similar average body weights among groups. Following a preliminary feeding period, mice were injected with 1 × 106 LNCaP cells (day 0) and sacrificed when tumors were ≥1,000 mm3.
Results
Two days before tumor injection, median NCKD body weight was 2.4 g (10%) and 2.1 g (8%) greater than the LFD and MCD groups, respectively (P < 0.0001). Diet was significantly associated with overall survival (log-rank P = 0.004). Relative to MCD, survival was significantly prolonged for the LFD (hazard ratio, 0.49; 95% confidence interval, 0.29–0.79; P = 0.004) and NCKD groups (hazard ratio, 0.59; 95% confidence interval, 0.37–0.93; P = 0.02). Median serum insulin, IGF-I, IGF-I/IGF binding protein-1 ratio, and IGF-I/IGF binding protein-3 ratio were significantly reduced in NCKD relative to MCD mice. Phospho-AKT/total AKT ratio and pathways associated with antiapoptosis, inflammation, insulin resistance, and obesity were also significantly reduced in NCKD relative to MCD tumors.
Conclusions
These results support further preclinical exploration of carbohydrate restriction in prostate cancer and possibly warrant pilot or feasibility testing in humans.
doi:10.1158/1940-6207.CAPR-08-0188
PMCID: PMC3774034  PMID: 19470786
12.  Apolipoprotein E gene polymorphism influences aggressive behavior in prostate cancer cells by deregulating cholesterol homeostasis  
International Journal of Oncology  2013;43(4): 1002 - 1010 .
High circulating cholesterol and its deregulated homeostasis may facilitate prostate cancer progression. Genetic polymorphism in Apolipoprotein (Apo) E, a key cholesterol regulatory protein may effect changes in systemic cholesterol levels. In this investigation, we determined whether variants of the Apo E gene can trigger defective intracellular cholesterol efflux, which could promote aggressive prostate cancer. ApoE genotypes of weakly (non-aggressive), moderate and highly tumorigenic (aggressive) prostate cancer cell lines were characterized, and we explored whether the ApoE variants were associated with tumor aggressiveness generated by intra cellular cholesterol imbalance, using the expression of caveolin-1 (cav-1), a pro-malignancy surrogate of cholesterol overload. Restriction isotyping of ApoE isoforms revealed that the non-aggressive cell lines carried ApoE ε3/ε3 or ε3/ε4 alleles, while the aggressive cell lines carried the Apoε2/ε4 alleles. Our data suggest a contrast between the non-aggressive and the aggressive prostate cancer cell lines in the pattern of cholesterol efflux and cav-1 expression. Our exploratory results suggest a relationship between prostate aggressiveness, ApoE isoforms and cholesterol imbalance. Further investigation of this relationship may elucidate the molecular basis for considering cholesterol as a risk factor of aggressive prostate tumors, and underscore the potential of the dysfunctional ApoE2/E4 isoform as a biomarker of aggressive disease.
doi: 10.3892/ijo.2013.2057
PMCID: PMC3829771  PMID: 23934233
prostate cancer ;  apolipoprotein E ;  alleles ;  cholesterol ;  aggressive ;  caveolin-1 ;  polymorphism ;  genotype ;  phenotype
13.  The Role of Obesity in Cancer Survival and Recurrence 
Obesity and components of energy imbalance, i.e., excessive energy intake and suboptimal levels of physical activity, are established risk factors for cancer incidence. Accumulating evidence suggests that these factors also may be important after the diagnosis of cancer and influence the course of disease, as well as overall health, well-being, and survival. Lifestyle and medical interventions that effectively modify these factors could potentially be harnessed as a means of cancer control. However, for such interventions to be maximally effective and sustainable, broad sweeping scientific discoveries ranging from molecular and cellular advances, to developments in delivering interventions on both individual and societal levels are needed. This review summarizes key discussion topics that were addressed in a recent Institute of Medicine Workshop entitled, “The Role of Obesity in Cancer Survival and Recurrence”; discussions included: 1) mechanisms associated with obesity and energy balance that influence cancer progression; 2) complexities of studying and interpreting energy balance in relation to cancer recurrence and survival; 3) associations between obesity and cancer risk, recurrence, and mortality; 4) interventions that promote weight loss, increased physical activity, and negative energy balance as a means of cancer control; and 5) future directions.
doi:10.1158/1055-9965.EPI-12-0485
PMCID: PMC3415558  PMID: 22695735
neoplasms; obesity; diet; physical activity; survival; recurrence
14.  Harvest for Health Gardening Intervention Feasibility Study in Cancer Survivors 
Acta oncologica (Stockholm, Sweden)  2013;52(6):1110-1118.
Background
Cancer survivors are at increased risk for second malignancies, cardiovascular disease, diabetes, and functional decline. Evidence suggests that a healthful diet and physical activity may reduce the risk of chronic disease and improve health in this population.
Methods
We conducted a feasibility study to evaluate a vegetable gardening intervention that paired 12 adult and child cancer survivors with Master Gardeners to explore effects on fruit and vegetable intake, physical activity, quality-of-life, and physical function. Throughout the year-long study period, the survivor-Master Gardener dyads worked together to plan/plant 3 gardens, harvest/rotate plantings, and troubleshoot/correct problems. Data on diet, physical activity, and quality-of-life were collected via surveys; anthropometrics and physical function were objectively measured. Acceptability of the intervention was assessed with a structured debriefing survey.
Results
The gardening intervention was feasible (robust enrollment; minimal attrition) and well-received by cancer survivors and Master Gardeners. Improvement in 3 of 4 objective measures of strength, agility, and endurance was observed in 90% of survivors, with the following change scores (median [interquartile range]) noted between baseline and 1-year follow-up: hand grip test (+4.8 [3.0, 6.7] kg), 8 foot Get-Up-and-Go (−1.0 [−1.8, −0.2] seconds), 30-second chair stand (+3.0 [−1.0, 5.0] stands), and 6-minute walk (+38 [20, 160] feet). Increases of ≥1 fruit and vegetable serving/ day and ≥30 minutes/week of physical activity were observed in 40% and 60%, respectively.
Conclusion
These preliminary results support the feasibility and acceptability of a mentored gardening intervention and suggest that it may offer a novel and promising strategy to improve fruit and vegetable consumption, physical activity, and physical function in cancer survivors. A larger randomized controlled trial is needed to confirm our results.
doi:10.3109/0284186X.2013.770165
PMCID: PMC3718632  PMID: 23438359
cancer survivors; gardening; intervention; health; diet
15.  Lost in Transition and Losing Money, but perhaps too Hasty? 
Nature reviews. Urology  2011;9(1):14-16.
Cancer survivors represent a burgeoning patient population at risk for recurrence and co-morbidity. Their needs are great and we must find ways to deliver care that optimizes health, while not “breaking-the-bank.” Fragmentation of care contributes to higher health care costs. Strategies that reduce redundancy while preserving care quality are essential.
doi:10.1038/nrurol.2011.205
PMCID: PMC3721727  PMID: 22158595
16.  IGF2/H19 methylation at birth and risk of overweight and obesity in children 
The Journal of Pediatrics  2012;161(1):31-39.
Objective
To determine if aberrant DNA methylation at differentially methylated regions (DMRs) regulating Insulin-like Growth Factor 2 (IGF2) expression in umbilical cord blood (UCB) is associated with overweight or obesity in a multiethnic cohort.
Study design
UCB leukocytes of 204 infants born between 2005 and 2009 in Durham, NC were analyzed for DNA methylation at two IGF2 DMRs using Pyrosequencing. Anthropometric and feeding data were collected at age one year. Methylation differences were compared between children >85th percentile of CDC weight-for-age (WFA) and those ≤85th percentile of WFA at one year using generalized linear models, adjusting for post-natal caloric intake, maternal cigarette smoking and race/ethnicity.
Results
The methylation percentages at the H19 imprint center DMR was higher in infants with WFA>85th percentile (62.7%, 95%CI=59.9–65.5%) compared with infants with WFA≤85th percentile (59.3%, 95%CI=58.2–60.3), (p=0.02). At the intragenic IGF2 DMR, methylation levels were comparable between infants with WFA≤85th and those with WFA>85th percentile.
Conclusions
Our findings suggest that IGF2 plasticity may be mechanistically important in early childhood overweight or obese status. If confirmed in larger studies, findings suggest aberrant DNA methylation at sequences regulating imprinted genes may be useful identifiers of children at risk for early obesity.
doi:10.1016/j.jpeds.2012.01.015
PMCID: PMC3360130  PMID: 22341586
Obesity; Breast Feeding; Child; DNA Methylation; Epigenetics; Genetic; Insulin-Like Growth Factor II
17.  Enhancing Exercise Adherence for the Breast Cancer Survivors 
doi:10.1249/FIT.0b013e31825a6db6
PMCID: PMC3529940  PMID: 23275740
Exercise; Breast Neoplasms; Health Promotion; Women’s Health; Barriers
18.  Reach Out to Enhance Wellness Home-Based Diet-Exercise Intervention Promotes Reproducible and Sustainable Long-Term Improvements in Health Behaviors, Body Weight, and Physical Functioning in Older, Overweight/Obese Cancer Survivors 
Journal of Clinical Oncology  2012;30(19):2354-2361.
Purpose
Diet and exercise interventions have been tested in cancer survivors as a means to reduce late effects and comorbidity, but few have assessed adherence and health outcomes long term.
Methods
Between July 2005 and May 2007, the Reach Out to Enhance Wellness (RENEW) trial accrued 641 locoregionally staged, long-term (≥ 5 years from diagnosis) colorectal, breast, and prostate cancer survivors in the United States (21 states), Canada, and the United Kingdom. All participants were sedentary (< 150 minutes of physical activity [PA] a week), overweight or obese (body mass index, 25 to 40 kg/m2), and over age 65 years. The trial tested a diet-exercise intervention delivered via mailed print materials and telephone counseling. RENEW used a wait-list control, cross-over design (ie, participants received the year-long intervention immediately or after a 1-year delay), which allowed the opportunity to assess program efficacy (previously reported primary outcome), durability, and reproducibility (reported herein). Measures included diet quality (DQ), PA, BMI, and physical function (PF).
Results
No significant relapse was observed in the immediate-intervention arm for DQ, PA, and BMI; however, rates of functional decline increased when the intervention ceased. From year 1 to year 2, significant improvements were observed in the delayed-intervention arm; mean change scores in behaviors and BMI and PF slopes were as follows: DQ score, 5.2 (95% CI, 3.4 to 7.0); PA, 45.8 min/wk (95% CI, 26.9 to 64.6 min/wk); BMI, −0.56 (95% CI, −0.75 to −0.36); and Short Form-36 PF, −1.02 versus −5.52 (P < .001 for all measures). Overall, both arms experienced significant improvements in DQ, PA, and BMI from baseline to 2-year follow-up (P < .001).
Conclusion
Older cancer survivors respond favorably to lifestyle interventions and make durable changes in DQ and PA that contribute to sustained weight loss. These changes positively reorient functional decline trajectories during intervention delivery.
doi:10.1200/JCO.2011.40.0895
PMCID: PMC3675693  PMID: 22614994
20.  Maternal BMI, IGF-I Levels, and Birth Weight in African American and White Infants 
At birth, elevated IGF-I levels have been linked to birth weight extremes; high birth weight and low birth weight are risk factors for adult-onset chronic diseases including obesity, cardiovascular disease, and type 2 diabetes. We examined associations between plasma IGF-I levels and birth weight among infants born to African American and White obese and nonobese women. Prepregnancy weight and height were assessed among 251 pregnant women and anthropometric measurements of full term infants (≥37 weeks of gestation) were taken at birth. Circulating IGF-I was measured by ELISA in umbilical cord blood plasma. Linear regression models were utilized to examine associations between birth weight and high IGF-I, using the bottom two tertiles as referents. Compared with infants with lower IGF-I levels (≤3rd tertile), those with higher IGF-I levels (>3rd tertile) were 130 g heavier at birth, (β-coefficient = 230, se = 58.0, P = 0.0001), after adjusting for gender, race/ethnicity, gestational age, delivery route, maternal BMI and smoking. Stratified analyses suggested that these associations are more pronounced in infants born to African American women and women with BMI ≥30 kg/m2; the cross product term for IGF-I and maternal BMI was statistically significant (P ≤ 0.0004). Our findings suggest that the association between IGF-I levels and birth weight depends more on maternal obesity than African American race/ethnicity.
doi:10.1155/2013/191472
PMCID: PMC3686113  PMID: 23861689
21.  Dietary Patterns Differ between Urban and Rural Older, Long-Term Survivors of Breast, Prostate, and Colorectal Cancer and Are Associated with Body Mass Index 
Background
Older adult cancer survivors are at great er risk of cancer recurrence and other comorbidities that may be prevented through improved diet and weight management. The tertiary prevention needs of rural-dwelling survivors may be even greater, yet little is known about rural and urban differences in lifestyle factors among this high risk population.
Objectives
To compare dietary patterns of urban and rural cancer survivors and to examine associations of dietary patterns with BMI.
Design
A secondary analysis was performed of baseline data from the Reach Out to Enhance Wellness (RENEW) trial, a diet and exercise intervention among overweight, long-term (> 5y) older survivors of colorectal, breast, and prostate cancer. Survivors in the present analysis (n = 729) underwent two 45–60 minute telephone surveys, which included two 24-hour dietary recalls. Principal Components Analysis (PCA) and multivariable general linear models were used to derive dietary patterns and to evaluate associations between dietary patterns and BMI, respectively.
Results
PCA identified three primary dietary patter ns among rural dwellers (“high sweets and starches”, “high reduced-fat dairy, cereal, nuts, and fruits”, and “mixed”) and three among urban dwellers (“high fruits and vegetables”, “high meat and refined grains”, and “high sugar-sweetened beverages”). Among rural survivors, greater adherence to the “high reduced-fat dairy, cereal, nuts, and fruits” pattern was positively associated with lower BMI (p-trend < 0.05) whereas higher scores on the “mixed” pattern was associated with greater BMI (p-trend < 0.05). Greater adherence to the “high fruits and vegetables” pattern among urban survivors was inversely associated with BMI (p-trend < 0.05).
Conclusions
Urban and rural differences in dietary intake behavior should be considered in designing public health interventions among the increasing population of older cancer survivors. Furthermore, targeting overall dietary patterns may be one approach to help reduce the burden of obesity among this population.
doi:10.1016/j.jand.2012.02.021
PMCID: PMC3378989  PMID: 22709810
dietary patterns; cancer survivors; body mass index; geographic residence
22.  Exercise and Cancer Treatment Symptoms in 408 Newly Diagnosed Older Cancer Patients 
Journal of geriatric oncology  2012;3(2):90-97.
While the benefits of exercise for managing cancer-and treatment-related side effects has been shown among various populations of cancer survivors, a relative dearth of information exists among older cancer patients.
Objectives
To determine the prevalence of exercise participation during and after primary cancer treatment in older (≥65 years) and the oldest (≥80 years) cancer patients and to examine the relationships between exercise, symptoms, and self-rated health (SRH).
Materials and Methods
408 newly diagnosed older cancer patients (mean age=73, range=65-92) scheduled to receive chemotherapy and/or radiation therapy reported symptoms and SRH prior to, during, and 6 months after treatment, and exercise participation during and following treatment.
Results
Forty-six percent of older and 41% of the oldest patients reported exercising during treatment. Sixty percent of older and 68% of the oldest patients reported exercising in the 6 months thereafter. Older patients who exercised during treatment reported less shortness of breath and better SRH during treatment, and better SRH following treatment. The oldest patients who exercised during treatment reported less memory loss and better SRH during treatment and less fatigue and better SRH following treatment. The oldest patients who exercised following treatment reported less fatigue, skin problems, and total symptom burden following treatment.
Conclusion
These data suggest a willingness of older cancer patients to attempt exercise during and after treatment. Exercise during these times is associated with less severe symptoms; further clinical research examining the efficacy of formal exercise interventions to reduce symptoms and improve SRH in older cancer patients is needed.
doi:10.1016/j.jgo.2012.01.002
PMCID: PMC3376161  PMID: 22712028
elderly; exercise; physical activity; neoplasms; side effects; symptoms; chemotherapy; radiation therapy
23.  Social, Demographic, and Medical Influences on Physical Activity in Child and Adolescent Cancer Survivors 
Journal of Pediatric Psychology  2011;37(2):198-208.
Objective This study evaluated associations between social, environmental, demographic, and medical predictors, and child and adolescent survivors’ physical activity (PA). Methods A structured telephone survey was conducted with 105 caregiver–survivor (aged 8–16 years) pairs and 36 caregivers of younger survivors (aged 6–7 years) alone. Participants completed measures assessing survivor PA and proposed predictors of PA including demographic, medical, social, and environmental influences. Results Social influences, including family PA, family support for PA, and peer support for PA, emerged as unique predictors of survivor PA. These variables predicted PA after controlling for demographic and medical factors. Child survivors’ PA was more strongly predicted by family influences while adolescent survivors’ PA was more strongly influenced by family and peer influences. Conclusions Child and adolescent survivors’ PA is strongly influenced by social factors. This finding parallels results with healthy children. PA interventions should focus on family and peer support to increase survivors’ PA behaviors.
doi:10.1093/jpepsy/jsr085
PMCID: PMC3282282  PMID: 22004885
adolescents; cancer and oncology; children; developmental perspectives; health behavior
24.  Current Evidence Linking Polyunsaturated Fatty Acids with Cancer Risk and Progression 
Frontiers in Oncology  2013;3:224.
There is increasing evidence that polyunsaturated fatty acids (PUFAs) play a role in cancer risk and progression. The n-3 family of PUFAs includes alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) while the n-6 family includes linolenic acid (LA) and arachidonic acid (AA). EPA and DHA are precursors for anti-inflammatory lipid mediators while AA is a precursor for pro-inflammatory lipid mediators. Collectively, PUFAs play crucial roles in maintaining cellular homeostasis, and perturbations in dietary intake or PUFA metabolism could result in cellular dysfunction and contribute to cancer risk and progression. Epidemiologic studies provide an inconsistent picture of the associations between dietary PUFAs and cancer. This discrepancy may reflect the difficulties in collecting accurate dietary data; however, it also may reflect genetic variation in PUFA metabolism which has been shown to modify physiological levels of PUFAs and cancer risk. Also, host-specific mutations as a result of cellular transformation could modify metabolism of PUFAs in the target-tissue. Clinical trials have shown that supplementation with PUFAs or foods high in PUFAs can affect markers of inflammation, immune function, tumor biology, and prognosis. Pre-clinical investigations have begun to elucidate how PUFAs may mediate cell proliferation, apoptosis and angiogenesis, and the signaling pathways involved in these processes. The purpose of this review is to summarize the current evidence linking PUFAs and their metabolites with cancer and the molecular mechanisms that underlie this association. Identifying the molecular mechanism(s) through which PUFAs affect cancer risk and progression will provide an opportunity to pursue focused dietary interventions that could translate into the development of personalized diets for cancer control.
doi:10.3389/fonc.2013.00224
PMCID: PMC3761560  PMID: 24027672
polyunsaturated fatty acids; cancer; pre-clinical testing; epidemiologic studies; clinical trials as topic; clinical trials; phase II as topic; review of literature
25.  Prostatic Alpha-Linolenic Acid (ALA) Is Positively Associated with Aggressive Prostate Cancer: A Relationship Which May Depend on Genetic Variation in ALA Metabolism 
PLoS ONE  2012;7(12):e53104.
Previous observational studies have reported associations between prostate cancer and alpha-linolenic acid (ALA). However, few investigations have been able to study this relationship prospectively and in well-controlled settings. Moreover, no studies have determined whether single nucleotide polymorphisms (SNPs) that influence ALA metabolism are associated with this common cancer. The purpose of this study was to explore associations between prostatic levels of ALA, SNPs and prostate cancer-specific biomarkers in samples collected from a previous randomized clinical trial conducted using a presurgical model and which tested the effects of flaxseed supplementation, a rich source of ALA, prior to prostatectomy (n = 134). Serum prostate-specific antigen (PSA) was determined and immunohistochemistry was used to assess tumor proliferation rate (Ki67). Prostatic ALA was determined with gas chromatography. Seven previously identified SNPs associated with delta-6 desaturase activity (rs99780, rs174537, rs174545, rs174572, rs498793, rs3834458 and rs968567) were tested for associations with prostatic ALA, PSA and Ki67. Despite consuming seven times more ALA per day, men in the flaxseed arm had similar amounts of prostatic ALA relative to men not consuming flaxseed. In unadjusted analysis, there were significant positive associations between prostatic ALA and PSA (ρ = 0.191, p = 0.028) and Ki67 (ρ = 0.186, p = 0.037). After adjusting for covariates (flaxseed, age, race, BMI and statin-use) the association between ALA and PSA remained (p = 0.004) but was slightly attenuated for Ki67 (p = 0.051). We did not observe associations between any of the SNPs studied and prostatic ALA; however, in models for PSA there was a significant interaction between rs498793 and ALA and for Ki67 there were significant interactions with ALA and rs99780 and rs174545. Independent and inverse associations were observed between rs174572 and Ki67. This study provides evidence that prostatic ALA, independent of the amount of ALA consumed, is positively associated with biomarkers of aggressive prostate cancer and that genetic variation may modify this relationship.
doi:10.1371/journal.pone.0053104
PMCID: PMC3532426  PMID: 23285256

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