Exercise as Medicine for People with a Substance Use Disorder: An ACSM Call to Action Statement.

ABSTRACT: Over 20 million Americans are living with a substance use disorder (SUD) and nearly 100,000 die annually from drug overdoses, with a majority involving an opioid. Many people with SUD have co-occurring chronic pain and/or a mental health disorder. Exercise is a frontline treatment for chronic pain and is an effective strategy for reducing depression and anxiety and improving overall mental health. Several studies have shown that exercise improves SUD-related outcomes including abstinence; however, there is limited large-scale randomized clinical trial evidence to inform integration of exercise into practice. In this Call to Action, we aim to raise awareness of the specific issues that should be addressed to advance exercise as medicine in people with SUD including the challenges of co-occurring chronic pain, mental illness, and cardiopulmonary health conditions. In addition, specialized training for exercise professionals and other support staff should be provided on these issues, as well as on the multiple dimensions of stigma that can impair engagement in treatment and overall recovery in people with SUD.

A randomized controlled trial of the effect of supervised exercise on functional outcomes in older African American and non-Hispanic White breast cancer survivors: Are there racial differences in the effects of exercise on functional outcomes?

BACKGROUND: The objective of this study was to test the hypothesis that exercise would be more effective than a support group plus Fitbit (SG+Fitbit) program in improving functional outcomes in older breast cancer survivors (BCSs) and that race would moderate the exercise effect on outcomes. METHODS: Older African American (AA) and non-Hispanic White (NHW) BCSs were purposively recruited and enrolled into the 52-week randomized controlled trial. The interventions included 20 weeks of supervised moderate-intensity aerobic and resistance training followed by 32 weeks of unsupervised exercise called IMPROVE (n = 108) and a 20-week SG+Fitbit program followed by 32 weeks of unsupervised activity (n = 105). Study outcomes were assessed at 20 and 52 weeks. The primary outcome was the change in Short Physical Performance Battery (SPPB) scores 20 weeks from the baseline between arms. Secondary outcomes included change in the 6-Minute Walk Test (6MWT) in meters 20 weeks from the baseline between arms. General linear regression and multivariable logistic regression analyses were used. RESULTS: The mean age was 71.9 years (SD, 5.9 years), and 44% were AA. SPPB scores did not differ between arms (adjusted difference in mean change, 0.13; 95% CI, -0.28 to 0.55; P = .53). However, the exercise arm (vs the SG+Fitbit arm) improved on the 6MWT (21.6 m; 95% CI, 2.5-40.6 m; P = .03). Race moderated the exercise effect on the 6MWT (adjusted interaction effect, 43.3 m; 95% CI, 6.3-80.2 m; P = .02); this implied that the change in the adjusted mean for the 6MWT at 20 weeks from the baseline was 43.3 m higher in AA exercise participants versus NHW exercise participants. CONCLUSIONS: Combined aerobic and resistance exercise appears to improve physical performance in older BCSs, and the exercise effect might be moderated by race, with AAs appearing to derive larger benefits in comparison with NHWs. Larger studies are warranted to confirm the study findings.

IMPROVE, a community-based exercise intervention versus support group to improve functional and health outcomes among older African American and Non-Hispanic White breast cancer survivors from diverse socioeconomic backgrounds: Recruitment strategies and baseline characteristics.

BACKGROUND: Behavioral intervention studies in older breast cancer survivors, particularly older African American (AA) and socioeconomic status-disadvantaged breast cancer survivors, are lacking. To inform future studies, the authors examined recruitment strategies in older breast cancer survivors who participated in an exercise intervention study. METHODS: IMPROVE is a randomized trial designed to evaluate a group-based exercise intervention versus a support group (ClinicalTrials.gov identifier, NCT02763228). Participants were aged ≥65 years who had survived stage I through III breast cancer and were within 5 years of treatment completion. Participants were recruited through multiple approaches, including peripheral, linguistic, and constituent-involving strategies that incorporated the identification of potentially eligible patients from 3 local hospitals and from State of Ohio registries and through direct clinician and community organization referrals. RESULTS: Between October 2016 and November 2019, 7487 patients were screened, 4790 were potentially eligible, and 213 were randomized into the study. The eligible:randomization rates were 4.4% overall and 84%, 8%, and 2% for recruitment using direct referrals, hospital registries, and state registries, respectively. The median age of the randomized cohort was 70 years (range, 65-88 years) and included 44% AA and 44% socioeconomic status-disadvantaged breast cancer survivors. Compared with all registry-eligible patients, directly referred-eligible patients were more likely to be AA versus Non-Hispanic White (41% vs 19%; P = .006), to be contacted successfully (100% vs 33%; P < .0001), and to accept study participation (88% vs 16%; P < .0001). CONCLUSIONS: Direct referrals appeared to be the most efficient strategy for recruiting AA survivors. Behavioral intervention studies seeking to target older AA and socioeconomic status-disadvantaged breast cancer survivors should include strategies that foster direct referrals to study participation.

Sleep, quality of life, and depression in endometrial cancer survivors with obesity seeking weight loss.

PURPOSE: Incidence and mortality rates of uterine cancer are increasing and, obesity, which is also rising, has been associated with uterine cancer development and mortality. A recent study found that poor sleep quality is common among endometrial cancer survivors and those with obesity had more sleep disturbances than those having normal weight. However, it is unclear if higher levels of obesity (Class III, BMI ≥ 40 kg/m2), which are rising rapidly, are differentially associated with sleep as well as depression and quality of life in endometrial cancer survivors. METHODS: We evaluated sleep, depression, and quality of life in 100 Stage I endometrial cancer survivors with obesity seeking weight loss enrolled in a lifestyle intervention (NCT01870947) at baseline. RESULTS: The average age was 60 years and mean BMI was 42.1 kg/m2 with 58% having a BMI ≥ 40 kg/m2. Most survivors (72.3%) had poor sleep quality and most (71.2%) reported sleeping < 7 h/night. Survivors with class III compared with class I obesity had significantly more sleep disturbances and daytime dysfunction; and, those with poor sleep had higher depression and lower quality of life. Survivors with a BMI ≥ 50 kg/m2 (~ 25%) had the highest levels of depression and lowest physical and emotional well-being. CONCLUSIONS: Our results reveal that endometrial cancer survivors with class III compared with class I obesity have poorer sleep quality, higher depression, and lower quality of life. Given the rising rates of obesity and uterine cancer mortality, interventions to combat both obesity and poor sleep are needed.

Meta-analysis of loci associated with age at natural menopause in African-American women.

Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA.

Genome-wide association study of age at menarche in African-American women.

African-American (AA) women have earlier menarche on average than women of European ancestry (EA), and earlier menarche is a risk factor for obesity and type 2 diabetes among other chronic diseases. Identification of common genetic variants associated with age at menarche has a potential value in pointing to the genetic pathways underlying chronic disease risk, yet comprehensive genome-wide studies of age at menarche are lacking for AA women. In this study, we tested the genome-wide association of self-reported age at menarche with common single-nucleotide polymorphisms (SNPs) in a total of 18 089 AA women in 15 studies using an additive genetic linear regression model, adjusting for year of birth and population stratification, followed by inverse-variance weighted meta-analysis (Stage 1). Top meta-analysis results were then tested in an independent sample of 2850 women (Stage 2). First, while no SNP passed the pre-specified P < 5 × 10(-8) threshold for significance in Stage 1, suggestive associations were found for variants near FLRT2 and PIK3R1, and conditional analysis identified two independent SNPs (rs339978 and rs980000) in or near RORA, strengthening the support for this suggestive locus identified in EA women. Secondly, an investigation of SNPs in 42 previously identified menarche loci in EA women demonstrated that 25 (60%) of them contained variants significantly associated with menarche in AA women. The findings provide the first evidence of cross-ethnic generalization of menarche loci identified to date, and suggest a number of novel biological links to menarche timing in AA women.

Dietary intake of calcium and magnesium and the metabolic syndrome in the National Health and Nutrition Examination (NHANES) 2001-2010 data.

Higher dietary intakes of Mg and Ca, individually, have been associated with a decreased risk for the metabolic syndrome (MetSyn). Experimental studies suggest that a higher intra-cellular ratio of Ca:Mg, which may be induced by a diet high in Ca and low in Mg, may lead to hypertension and insulin resistance. However, no previous epidemiological studies have examined the effects of the combined intake of Mg and Ca on MetSyn. Thus, we evaluated the association between dietary intakes of Ca and Mg (using 24-h recalls), independently and in combination, and MetSyn in the National Health and Nutrition Examination Study 2001-2010 data, which included 9148 adults (4549 men and 4599 women), with complete information on relevant nutrient, demographic, anthropometric and biomarker variables. We found an inverse association between the highest (>355 mg/d) v. the lowest (<197 mg/d) quartile of Mg and MetSyn (OR 0.70; 95% CI 0.57, 0.86). Women who met the RDA for both Mg (310-320 mg/d) and Ca (1000-1200 mg/d) had the greatest reduced odds of MetSyn (OR 0.59; 95% CI 0.45, 0.76). In men, meeting the RDA for Mg (400-420 mg/d) and Ca (1000-1200 mg/d), individually or in combination, was not associated with MetSyn; however, men with intakes in the highest quartile for Mg (≥ 386 mg/d) and Ca (≥ 1224 mg/d) had a lower odds of MetSyn (OR 0.74; 95% CI 0.59, 0.93). Our results suggest that women who meet the RDA for Mg and Ca have a reduced odds of MetSyn but men may require Ca levels higher than the RDA to be protected against MetSyn.

Case-only gene-environment interaction between ALAD tagSNPs and occupational lead exposure in prostate cancer.

BACKGROUND: Black men have historically had higher blood lead levels than white men in the U.S. and have the highest incidence of prostate cancer in the world. Inorganic lead has been classified as a probable human carcinogen. Lead (Pb) inhibits delta-aminolevulinic acid dehydratase (ALAD), a gene recently implicated in other genitourinary cancers. The ALAD enzyme is involved in the second step of heme biosynthesis and is an endogenous inhibitor of the 26S proteasome, a master system for protein degradation and a current target of cancer therapy. METHODS: Using a case-only study design, we assessed potential gene-environment (G × E) interactions between lifetime occupational Pb exposure and 11 tagSNPs within ALAD in black (N = 260) and white (N = 343) prostate cancer cases. RESULTS: Two ALAD tagSNPs in high linkage disequilibrium showed significant interaction with high Pb exposure among black cases (rs818684 interaction odds ratio or IOR = 2.73, 95% CI 1.43-5.22, P = 0.002; rs818689 IOR = 2.20, 95% CI 1.15-4.21, P = 0.017) and an additional tagSNP, rs2761016, showed G × E interaction with low Pb exposure (IOR = 2.08, 95% CI 1.13-3.84, P = 0.019). Further, the variant allele of rs818684 was associated with a higher Gleason grade in those with high Pb exposure among both blacks (OR 3.96, 95% CI 1.01-15.46, P = 0.048) and whites (OR 2.95, 95% CI 1.18-7.39, P = 0.020). CONCLUSIONS: Genetic variation in ALAD may modify associations between Pb and prostate cancer. Additional studies of ALAD, Pb, and prostate cancer are warranted and should include black men. Prostate 74:637-646, 2014. © 2014 Wiley Periodicals, Inc.

Gene-environment interactions between JAZF1 and occupational and household lead exposure in prostate cancer among African American men.

PURPOSE: A single nucleotide polymorphism, rs10486567, in JAZF1 has consistently been associated with increased risk of prostate cancer. The physical interaction of zinc finger proteins, such as JAZF1, with heavy metals may play a role in carcinogenesis. This study assessed potential gene-environment statistical interactions (G×E) between rs10486567 and heavy metals in prostate cancer. METHODS: In a case-only study of 228 African American prostate cancer cases, G×E between rs10486567 and sources of cadmium and lead (Pb) were assessed. Unconditional logistic regression was used to estimate interaction odds ratios (IORs), and generalized estimating equations were used for models containing nested data. Case-control validation of IORs was performed, using 82 controls frequency matched to cases on age-race. RESULTS: Among cases, a potential G×E interaction was observed between rs10486567 CC genotype and living in a Census tract with a high proportion of housing built before 1950, a proxy for household Pb exposure, when compared to CT or TT carriers (OR 1.81; 95% CI 1.04-3.16; p = 0.036). A stronger G×E interaction was observed when both housing and occupational Pb exposure were taken into account (OR 2.62; 95% CI 1.03-6.68; p = 0.04). Case-control stratified analyses showed the odds of being a CC carrier were higher in cases compared to controls among men living in areas with older housing (OR 2.03; CI 0.99-4.19; p = 0.05) or having high occupational Pb exposure (OR 2.50; CI 1.01-6.18; p = 0.05). CONCLUSIONS: In African American men, the association between JAZF1 rs10486567 and prostate cancer may be modified by exposure to heavy metals such as Pb.

Neural correlates of inhibitory control in severe class III compared with class I/II obesity using a sample of endometrial cancer survivors seeking weight loss.

OBJECTIVE: No prior studies have evaluated inhibitory control in people with severe class III compared with class I/II obesity. Thus, the study aim was to evaluate inhibitory control and neural correlates of response inhibition by obesity class using a sample of endometrial cancer (EC) survivors with obesity, who have a higher risk of overall but not cancer-specific mortality. METHODS: Forty-eight stage I EC survivors with obesity (class I/II: n = 21; class III: n = 27) seeking weight loss in a lifestyle intervention at baseline completed a stop signal task during functional magnetic resonance imaging. RESULTS: It was found that participants with class III obesity had a longer stop signal reaction time (mean [SD], 278.8 [51.3] vs. 251.5 [34.0] milliseconds, p < 0.01) compared with those with class I/II obesity, indicating that patients with EC with severe obesity had greater impulsivity and poorer inhibitory control. Results also showed increased activation in the thalamus and superior frontal gyrus for the incorrect versus correct inhibition contrast in class III but not class I/II obesity (whole brain cluster corrected, p < 0.05). CONCLUSIONS: These results provide novel insights into inhibitory control and corresponding neural correlates in severe versus less severe classes of obesity and highlight the importance of targeting inhibitory control processes in weight-loss interventions, particularly for people with severe obesity and greater impulsivity.

Barriers, perceived benefits and preferences to exercise in adults with an opioid use disorder in the U.S.

Introduction: Over 10 million Americans misuse opioids and more than 5 million have been diagnosed with an opioid use disorder (OUD). In 2021, over 100,000 Americans died of a drug overdose and more than 75% of these deaths involved an opioid. Exercise has been shown to increase abstinence and decrease anxiety and depression in people with a substance use disorder. However, only a few small trials have focused on persons with OUD who often experience additional challenges including chronic pain, mental health disorders and cardio-metabolic abnormalities. Methods: We aimed to describe the barriers, perceived benefits and preferences to exercise in adults with OUD in residential treatment in the U.S. as part of a larger study. We conducted 33 individually administered, semi-structured interviews and transcribed audiotapes verbatim, conducted coding and thematic analysis using NVivo v12 software (QSR International Inc.). Results: Our sample had nearly equal representation of males and females and, was predominantly Caucasian (88%) with a mean of age of 34.5 (s.d. 7.5) years old. Participants stated that exercise helps to reduce drug cravings, anxiety, depression and pain and improve mood, physical health and build "normalcy". Barriers included lack of time, access to resources, fear of poor health and triggering pain. Participants preferred moderate intensity exercise 3 times/week and 30-60 min sessions. Conclusions: Our findings indicate that adults with OUD believe exercise is a valuable tool to use in their recovery but they encounter several barriers. Many barriers, however, could be overcome with structured programs offered by residential treatment centers.

Food Insecurity and Nutritional Challenges in Adolescent and Young Adult Cancer Survivors in the U.S.A.: A Narrative Review and Call to Action.

Advancements in cancer treatments over the past several decades have led to improved cancer survival in adolescents and young adults (AYAs, ages 15-39 years). However, AYA cancer survivors are at an increased risk for "late effects", including cardiovascular, pulmonary and bone diseases as well as fatigue, infertility and secondary cancers. The treatments for cancer may also alter taste, lead to nutritional deficiencies and increase financial burdens that, when taken together, may increase the risk of food and nutrition security in AYA cancer survivors. Furthermore, although AYAs are often merged together in cancer survivorship studies, adolescents and young adults have distinct developmental, psychosocial and pathophysiological differences that may modify their risk of nutritional challenges. In this narrative review and "Call to Action", rationale is provided for why there is a need to better understand nutritional challenges and food insecurity in AYA cancer survivors as a special population. Then, recommendations for next steps to advance knowledge and policy in this field are provided. In particular, integrating screening for food and nutrition insecurity and enhancing awareness of existing resources (e.g., the Supplemental Nutrition Assistance Program, SNAP) might help AYA cancer survivors combat nutritional deficiencies and reduce late effects while improving their overall survival and quality of life.

Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19.

Importance: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective: To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures: Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures: The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results: The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance: This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration: ClinicalTrials.gov Identifier: NCT04354701.

Reduction in neural activation to high-calorie food cues in obese endometrial cancer survivors after a behavioral lifestyle intervention: a pilot study.

BACKGROUND: Obesity increases the risk of endometrial cancer (EC) and obese EC patients have the highest risk of death among all obesity-associated cancers. However, only two lifestyle interventions targeting this high-risk population have been conducted. In one trial, food disinhibition, as determined by the Three-Factor Eating Questionnaire, decreased post-intervention compared to baseline, suggesting an increase in emotional eating and, potentially, an increase in food related reward. Therefore, we evaluated appetitive behavior using functional magnetic resonance imaging (fMRI) and a visual food task in 8 obese, Stage I/II EC patients before and after a lifestyle intervention (Survivors in Uterine Cancer Empowered by Exercise and a Healthy Diet, SUCCEED), which aimed to improve nutritional and exercise behaviors over 16 group sessions in 6 months using social cognitive theory. RESULTS: Congruent to findings in the general obese population, we found that obese EC patients, at baseline, had increased activation in response to high- vs. low-calorie food cues after eating a meal in brain regions associated with food reward (insula, cingulate gyrus; precentral gyrus; whole brain cluster corrected, p < 0.05). At 6 months post-intervention compared to baseline, we observed decreased activation for the high-calorie vs. non-food contrast, post-meal, in regions involved in food reward and motivation (posterior cingulate, cingulate gyrus, lateral globus pallidus, thalamus; claustrum; whole brain cluster corrected, p < 0.05). CONCLUSIONS: Our preliminary results suggest behavioral lifestyle interventions may help to reduce high-calorie food reward in obese EC survivors who are at a high-risk of death. To our knowledge, this is the first study to demonstrate such changes.

Improving Surveillance and Epidemic Response in Ohio Childcare Settings.

At the start of the Coronavirus Disease of 2019 (COVID-19) pandemic, the risk of cases in childcare programs was unknown. Thus, a rapid-response research approach was launched in Ohio childcare settings. Passive surveillance data from a state-operated incident reporting system were evaluated to estimate the number of COVID-19 cases from 15 August 2020 to 1 January 2021. Additionally, active surveillance with self-administered reverse transcriptase-polymerase chain reaction (RT-PCR) tests were conducted among staff at 46 childcare programs. Finally, six zoom-based focus groups with program administrators were used to gain feedback. Staff and children in childcare settings contributed 0.38% and 0.15% of the COVID-19 cases in Ohio during this timeframe, respectively. RT-PCR testing identified 3 unrecognized cases (0.88% of tests), and all occurred when the statewide positivity rate was >5%. Focus groups revealed that access to affordable cleaning supplies, masks, and reliable staffing were critical. Perhaps most importantly, we conclude that expanding the incident reporting system to include a childcare census would allow for the tracking of future health problems with highly valuable incidence rate estimations.

FTO polymorphisms are associated with adult body mass index (BMI) and colorectal adenomas in African-Americans.

Obesity is a known risk factor for colon cancer and higher body mass index (BMI) has been associated with colorectal adenomas, which are precursor lesions to most colorectal cancers. Polymorphisms in the fat-mass and obesity-associated (FTO) gene have been associated with BMI and larger effects in older versus younger children have been reported. However, no studies have examined associations between FTO polymorphisms, BMI throughout adulthood and colorectal adenomas. Therefore, we evaluated associations between FTO polymorphisms (rs1421085, rs17817449, rs8050136, rs9939609, rs8044769), adult BMI (at recruitment, 50s, 40s, 30s, 20s age decades) and colorectal adenomas in 759 Caucasians and 469 African-Americans. We found that the highest versus the lowest BMI tertile at recruitment [odds ratio (OR) = 1.82; 95% confidence interval (CI): 1.07-2.16] and in the 30s (OR = 1.50; 95% CI: 1.04-2.15) was associated with higher adenoma risk. Stratification by ethnicity revealed that these associations only remained significant in Caucasians. We found that, in Caucasians, having two versus no copies of the variant allele in rs17817449, rs8050136 and rs9939609, which are all in strong linkage disequilibrium, was associated with higher BMI in the 30s and 40s but none of the polymorphisms were associated with adenomas. In African-Americans, having one or two copies of the variant in rs17817449 (OR = 0.61; 95% CI: 0.39-0.95) and rs8050136 (OR = 0.59; 95% CI: 0.38-0.93) was associated with colorectal adenomas and, having two variant copies in rs17817449 and rs8050136 was associated with higher BMI at recruitment and in the 40s, respectively. Our results are consistent with prior studies and show for the first time that FTO polymorphisms are associated with colorectal adenomas in African-Americans.

Higher bone mineral density is associated with a decreased risk of colorectal adenomas.

Bone mineral density (BMD) is a biomarker for cumulative exposure to multiple factors including estrogen, calcium, vitamin D and physical activity, which have all been independently associated with colorectal cancer. Furthermore, higher levels of BMD have been inversely associated with colorectal cancer risk, particularly in postmenopausal women. However, no prior studies have examined the potential association between BMD and colorectal adenomas, which are precursor lesions to most colorectal cancers. Therefore, we evaluated the association between BMD, which was measured using a whole body, dual-energy X-ray absorptiometry scan and colorectal adenomas in 167 patients who underwent colonoscopy screening. We found that patients in the highest tertile of total body BMD (>1.294 g/cm(2)) and in the middle tertile (≥1.167 to ≤1.294 g/cm(2)) compared to those with a total body BMD in the lowest tertile (<1.167 g/cm(2)) had a lower risk of colorectal adenomas (highest vs. lowest tertile: OR = 0.29 (0.10-0.84); middle vs. lowest tertile: OR=0.26 (0.08-0.80); p-trend=0.02). Stratification by gender revealed that this association was more pronounced in women (highest (>1.280 g/cm(2)) vs. lowest (<1.130 g/cm(2)) tertile: OR=0.08 (0.01-0.70); middle (≥1.130 to ≤1.280 g/cm(2)) vs. lowest tertile: OR=0.15 (0.04-0.94); p-trend=0.02) even after excluding hormone replacement therapy users (highest (>1.295 g/cm(2)) and middle (≥1.132 to ≤1.295 g/cm(2)) vs. lowest (<1.132 g/cm(2)) tertile: OR=0.17 (0.03-0.97); p-trend=0.04). Our results show, for the first time, that BMD is inversely associated with colorectal adenomas, particularly in women. Although additional larger, prospective studies are needed, our results suggest that BMD may be a biomarker for colorectal cancer precursor lesions.

Insights to the neural response to food cues in class III compared with class I and II obese adults using a sample of endometrial cancer survivors seeking weight loss.

BACKGROUND: The rates of severe or Class III obesity (BMI ≥ 40.0 kg/m2) and endometrial cancer (EC) incidence and mortality have been increasing significantly in the United States. Adults with severe obesity are more likely to die and women with severe obesity have a higher risk of EC development and mortality than those with Class I/II obesity (BMI: 30-<40 kg/m2). However, no prior studies have evaluated the neural response to food cues by obesity severity/class in adults with or without cancer. METHODS: We conducted a functional magnetic resonance imaging visual food cue task in 85 obese Stage I EC survivors who were seeking weight loss in a lifestyle intervention at baseline. We evaluated the neural response to high-calorie vs. non-food images after an overnight fast (fasted state) and after eating a standardized meal (fed state), and grouped patients by obesity class (Class I/II: n = 38; Class III: n = 47). RESULTS: In the fasted state, we found increased activation in several regions including the dorsolateral prefrontal cortex (DLPFC) in Class III and Class I/II patients (whole brain cluster corrected (WBCC), p < 0.05), which was significantly higher in Class III vs. Class I/II (p < 0.05). We found decreased activation in the insula in the fasted state, which was significantly lower in Class I/II vs. Class III (p = 0.03). In the fed state, we found increased activation in the DLPFC in Class III and Class I/II (WBCC, p < 0.05). The increased activation in cognitive control/inhibition regions (DLPFC) is consistent with the summative literature; however, the decreased activation in taste information processing regions (insula) was unexpected. CONCLUSIONS: Our results provide novel insights on food cue response between different classes of obesity and highlight the importance of targeting the DLPFC in weight loss interventions, particularly in severely obese patients. Additional studies examining food-related neural circuitry between different classes of obesity are needed.

IMPROVE, a community-based exercise intervention versus support group to improve functional and health outcomes among older African American and non-Hispanic White breast cancer survivors from diverse socioeconomic backgrounds: Rationale, design and methods.

BACKGROUND: African Americans (AA) and socioeconomic status (SES) disadvantaged older breast cancer survivors (BCS) are more likely to experience poor functional and health outcomes. However, few studies have evaluated the putative beneficial effects of exercise on these outcomes in older racial minority and SES-disadvantaged BCS. METHODS: This is a mixed-methods study that includes a randomized-controlled trial, "IMPROVE", to evaluate a group-based exercise intervention compared to a support group program in older BCS, followed by post-intervention semi-structured interviews to evaluate the intervention. The trial aims to recruit 220 BCS with 55 in each of four strata defined by race (AA versus Non-Hispanic Whites) and SES (disadvantaged vs. non-disadvantaged). Participants are ≥65 years old and within five years of treatment completion for stage I-III breast cancer. Participants are randomized to a 52-week, three sessions/week, one-hour/session, moderate intensity aerobic and resistance group exercise intervention, (n = 110) or a 52-week, one hour/week, support group intervention [attention-control arm], (n = 110). The first 20 weeks of both programs are supervised and the last 32 weeks, unsupervised. The primary outcome is the change in Short Physical Performance Battery (SPPB) Scores at 20 weeks from baseline, between the two arms. Secondary outcomes include change in SPPB scores at 52 weeks, change in body composition and biomarkers, at 20 and 52 weeks from baseline, between arms. DISCUSSION: Results of the trial may contribute to a better understanding of factors associated with recruitment, and acceptability, and will inform future exercise programs to optimally improve health outcomes for older BCS.

Polymorphisms in glutathione S-transferase genes increase risk of prostate cancer biochemical recurrence differentially by ethnicity and disease severity.

OBJECTIVE: Genetic polymorphisms that modify the detoxifying activity of glutathione S-transferases (GSTs) can affect the level of carcinogenic metabolites created by endogenous steroid hormones and exogenous chemical substances. Although the GSTM1 null genotype has been shown to increase prostate cancer mortality in Caucasians, potential associations between GST polymorphisms and prostate cancer biochemical recurrence (BCR) have not been well studied, particularly in African-Americans. METHODS: We examined potential associations between the GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphisms and BCR, after prostatectomy, in 168 African-American and 226 Caucasian patients treated at Henry Ford Hospital in Detroit, Michigan using Cox proportional hazards modeling. RESULTS: We found that African-Americans with the GSTT1 null genotype had increased BCR risk compared to those having GSTT1 present (hazard ratio (HR) = 2.30; 95% CI = 1.01­5.18; p = 0.04); and African-Americans with the GSTT1 null genotype and high grade tumors had an even greater risk (HR = 7.82; 95% CI = 2.49­24.50; p < 0.001). In Caucasians, an increased risk was observed in those patients with high grade tumors and the GSTM1 null genotype (HR = 2.88; 95% CI = 1.16­7.14; p = 0.02). Similar associations were observed for advanced stage and more aggressive (high grade or advanced stage) disease. CONCLUSION: Our results suggest GSTs may hold promise as therapeutic targets in more advanced prostate cancers, particularly, in African-Americans.