Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes: Analysis of the Look AHEAD Randomized Clinical Trial.

OBJECTIVE: This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. METHODS: Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. RESULTS: After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). CONCLUSIONS: An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.

Childhood hematologic cancer and residential proximity to oil and gas development.

BACKGROUND: Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design. METHODS: Participants were 0-24 years old, living in rural Colorado, and diagnosed with cancer between 2001-2013. For each child in our study, we calculated inverse distance weighted (IDW) oil and gas well counts within a 16.1-kilometer radius of residence at cancer diagnosis for each year in a 10 year latency period to estimate density of oil and gas development. Logistic regression, adjusted for age, race, gender, income, and elevation was used to estimate associations across IDW well count tertiles for 87 acute lymphocytic leukemia (ALL) cases and 50 non-Hodgkin lymphoma (NHL) cases, compared to 528 controls with non-hematologic cancers. FINDINGS: Overall, ALL cases 0-24 years old were more likely to live in the highest IDW well count tertiles compared to controls, but findings differed substantially by age. For ages 5-24, ALL cases were 4.3 times as likely to live in the highest tertile, compared to controls (95% CI: 1.1 to 16), with a monotonic increase in risk across tertiles (trend p-value = 0.035). Further adjustment for year of diagnosis increased the association. No association was found between ALL for children aged 0-4 years or NHL and IDW well counts. While our study benefited from the ability to select cases and controls from the same population, use of cancer-controls, the limited number of ALL and NHL cases, and aggregation of ages into five year ranges, may have biased our associations toward the null. In addition, absence of information on O&G well activities, meteorology, and topography likely reduced temporal and spatial specificity in IDW well counts. CONCLUSION: Because oil and gas development has potential to expose a large population to known hematologic carcinogens, further study is clearly needed to substantiate both our positive and negative findings. Future studies should incorporate information on oil and gas development activities and production levels, as well as levels of specific pollutants of interest (e.g. benzene) near homes, schools, and day care centers; provide age-specific residential histories; compare cases to controls without cancer; and address other potential confounders, and environmental stressors.

The Interaction between Genetic Ancestry and Breast Cancer Risk Factors among Hispanic Women: The Breast Cancer Health Disparities Study.

Background: Hispanic women have lower breast cancer incidence rates than non-Hispanic white (NHW) women. To what extent genetic versus nongenetic factors account for this difference is unknown.Methods: Using logistic regression, we evaluated the interactive influences of established risk factors and ethnicity (self-identified and identified by ancestral informative markers) on breast cancer risk among 2,326 Hispanic and 1,854 NHW postmenopausal women from the United States and Mexico in the Breast Cancer Health Disparities Study.Results: The inverse association between the percentage of Native American (NA) ancestry and breast cancer risk was only slightly attenuated after adjusting for known risk factors [lowest versus highest quartile: odds ratio (OR) =1.39, 95% confidence interval (CI) = 1.00-1.92 among U.S. Hispanics; OR = 1.92 (95% CI, 1.29-2.86) among Mexican women]. The prevalence of several risk factors, as well as the associations with certain factors and breast cancer risk, differed according to genetic admixture. For example, higher body mass index (BMI) was associated with reduced risk among women with lower NA ancestry only [BMI <25 versus >30: OR = 0.65 (95% CI, 0.44-0.98) among U.S. Hispanics; OR = 0.53 (95% CI, 0.29-0.97) among Mexicans]. The average number of risk factors among cases was inversely related to the percentage of NA ancestry.Conclusions: The lower NA ancestry groups were more likely to have the established risk factors, with the exception of BMI. Although the majority of factors were associated with risk in the expected directions among all women, BMI had an inverse association among Hispanics with lower NA ancestry.Impact: These data suggest that the established risk factors are less relevant for breast cancer development among women with more NA ancestry. Cancer Epidemiol Biomarkers Prev; 26(5); 692-701. ©2016 AACR.

The American Cancer Society challenge goal to reduce US cancer mortality by 50% between 1990 and 2015: Results and reflections.

In 1996, the Board of Directors of the American Cancer Society (ACS) challenged the United States to reduce what looked to be possible peak cancer mortality in 1990 by 50% by the year 2015. This analysis examines the trends in cancer mortality across this 25-year challenge period from 1990 to 2015. In 2015, cancer death rates were 26% lower than in 1990 (32% lower among men and 22% lower among women). The 50% reduction goal was more fully met for the cancer sites for which there was enactment of effective approaches for prevention, early detection, and/or treatment. Among men, mortality rates dropped for lung cancer by 45%, for colorectal cancer by 47%, and for prostate cancer by 53%. Among women, mortality rates dropped for lung cancer by 8%, for colorectal cancer by 44%, and for breast cancer by 39%. Declines in the death rates of all other cancer sites were substantially smaller (13% among men and 17% among women). The major factors that accounted for these favorable trends were progress in tobacco control and improvements in early detection and treatment. As we embark on new national cancer goals, this recent past experience should teach us that curing the cancer problem will require 2 sets of actions: making new discoveries in cancer therapeutics and more completely applying those discoveries in cancer prevention we have already made. CA Cancer J Clin 2016;66:359-369. © 2016 American Cancer Society.

Impact of a behavioral weight loss intervention on comorbidities in overweight and obese breast cancer survivors.

PURPOSE: Comorbid medical conditions are common among breast cancer survivors, contribute to poorer long-term survival and increased overall mortality, and may be ameliorated by weight loss. This secondary analysis evaluated the impact of a weight loss intervention on comorbid medical conditions immediately following an intervention (12 months) and 1-year postintervention (24 months) using data from the Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) trial-a phase III trial which was aimed at and successfully promoted weight loss. METHODS: ENERGY randomized 692 overweight/obese women who had completed treatment for early stage breast cancer to either a 1-year group-based behavioral intervention designed to achieve and maintain weight loss or to a less intensive control intervention. Minimal support was provided postintervention. New medical conditions, medical conditions in which non-cancer medications were prescribed, hospitalizations, and emergency room visits, were compared at baseline, year 1, and year 2. Changes over time were analyzed using chi-squared tests, Kaplan-Meier, and logistic regression analyses. RESULTS: At 12 months, women randomized to the intervention had fewer new medical conditions compared to the control group (19.6 vs. 32.2 %, p < 0.001); however, by 24 months, there was no longer a significant difference. No difference was observed in each of the four conditions for which non-cancer medications were prescribed, hospital visits, or emergency visits at either 12 or 24 months. CONCLUSIONS: These results support a short-term benefit of modest weight loss on the likelihood of comorbid conditions; however, recidivism and weight regain likely explain no benefit at 1-year postintervention follow-up.

Surveillance and beliefs about follow-up care among long-term breast cancer survivors: a comparison of primary care and oncology providers.

PURPOSE: Delivery of follow-up care to breast cancer survivors is an important public health issue due to their increasing number and the anticipated shortage of oncology providers. This study evaluated adherence to American Society of Clinical Oncology (ASCO)-recommended surveillance tests in a bi-ethnic cohort of long-term breast cancer survivors. METHODS: Women (n = 298) in Arizona and Colorado who had previously participated in a population-based study of breast cancer were enrolled into a follow-up survey approximately 6 years post-diagnosis. ASCO-recommended surveillance (mammogram, clinical breast, and physical exam), other non-recommended tests (e.g. tumor markers, imaging scans), and patients' beliefs were compared by provider type using multivariate logistic regression. RESULTS: No significant differences in patient self-report of physical exam or mammography prevalence by provider type was observed after adjustment for covariates. Receipt of surveillance tests not recommended by ASCO was higher among survivors who saw an oncologist (tumor marker tests: OR = 3.0, 95 % CI 1.5-5.8; and other blood tests: OR = 2.0, 95 % CI 1.1-3.5) as compared to those who routinely see a primary care physician. These observed differences persisted after adjustment for age, stage, lapse in insurance, education, or ethnicity. CONCLUSIONS: Although overutilization of non-recommended tests was observed among women who saw an oncologist, the majority of breast cancer survivors received ASCO-recommended surveillance regardless of provider type. IMPLICATIONS FOR CANCER SURVIVORS: Most breast cancer survivors receive recommended surveillance tests, whether their care is managed by a primary care physician or an oncologist, but some women receive unnecessary testing. Women should talk with their providers about tests recommended based on their past breast cancer diagnosis.

Project TEACH: A Capacity-Building Training Program for Community-Based Organizations and Public Health Agencies.

Project TEACH (Teaching Equity to Advance Community Health) is a capacity-building training program to empower community-based organizations and regional public health agencies to develop data-driven, evidence-based, outcomes-focused public health interventions. TEACH delivers training modules on topics such as logic models, health data, social determinants of health, evidence-based interventions, and program evaluation. Cohorts of 7 to 12 community-based organizations and regional public health agencies in each of the 6 Colorado Area Health Education Centers service areas participate in a 2-day training program tailored to their specific needs. From July 2008 to December 2011, TEACH trained 94 organizations and agencies across Colorado. Training modules were well received and resulted in significant improvement in knowledge in core content areas, as well as accomplishment of self-proposed organizational goals, grant applications/awards, and several community-academic partnerships.

Quality of life outcomes from the Exercise and Nutrition Enhance Recovery and Good Health for You (ENERGY)-randomized weight loss trial among breast cancer survivors.

Obesity is a poor prognostic factor and is negatively related to quality of life (QOL) in breast cancer survivors. Exercise and Nutrition to Enhance Recovery and Good Health for You is the largest weight loss trial completed among cancer survivors. Percent losses in body weight with an intensive group-based intervention versus an attention control were 6.0 versus 1.5 % (p < 0.0001) and 3.7 versus 1.3 % (p < 0.0001) at 12 and 24 months, respectively. ENERGY also was designed to answer the research question: Does weight loss significantly improve vitality and physical function (key components of QOL)? 692 breast cancer survivors (BMI: 25-45 kg/m(2)) at 4 US sites were randomized to a year-long intensive intervention of 52 group sessions and telephone counseling contacts versus a non-intensive (control) of two in-person counseling sessions. Weight, self-reported QOL, and symptoms were measured semi-annually for two years. Significant decreases in physical function and increases in symptoms were observed among controls from baseline to 6 months, but not in the intervention arm, -3.45 (95 % Confidence Interval [CI] -6.10, -0.79, p = 0.0109) and 0.10 (95 %CI 0.04, 0.16, p = 0.0021), respectively. Improvements in vitality were seen in both arms but trended toward greater improvement in the intervention arm -2.72 (95 % CI -5.45, 0.01, p = 0.0508). These differences diminished over time; however, depressive symptoms increased in the intervention versus control arms and became significant at 24 months, -1.64 (95 % CI -3.13, -0.15, p = 0.0308). Increased QOL has been reported in shorter term diet and exercise trials among cancer survivors. These longer term data suggest that diet and exercise interventions improve some aspects of QOL, but these benefits may diminish over time.

Results of the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial: A Behavioral Weight Loss Intervention in Overweight or Obese Breast Cancer Survivors.

PURPOSE: Obesity increases risk for all-cause and breast cancer mortality and comorbidities in women who have been diagnosed and treated for breast cancer. The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) study is the largest weight loss intervention trial among survivors of breast cancer to date. METHODS: In this multicenter trial, 692 overweight/obese women who were, on average, 2 years since primary treatment for early-stage breast cancer were randomly assigned to either a group-based behavioral intervention, supplemented with telephone counseling and tailored newsletters, to support weight loss or a less intensive control intervention and observed for 2 years. Weight and blood pressure were measured at 6, 12, 18, and 24 months. Longitudinal mixed models were used to analyze change over time. RESULTS: At 12 months, mean weight loss was 6.0% of initial weight in the intervention group and 1.5% in the control group (P<.001). At 24 months, mean weight loss in the intervention and control groups was 3.7% and 1.3%, respectively (P<.001). Favorable effects of the intervention on physical activity and blood pressure were observed. The weight loss intervention was more effective among women older than 55 years than among younger women. CONCLUSION: A behavioral weight loss intervention can lead to clinically meaningful weight loss in overweight/obese survivors of breast cancer. These findings support the need to conduct additional studies to test methods that support sustained weight loss and to examine the potential benefit of intentional weight loss on breast cancer recurrence and survival.

Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma.

BACKGROUND: Inflammatory cytokines in the colonic microenvironment have been shown to increase with advance colorectal cancer disease state. However, the contribution of inflammatory cytokines to pre-malignant disease, such as the formation of adenomas, is unclear. METHODS: Using the Milliplex® MAP Human Cytokine/ Chemokine Magnetic Bead Panel Immunoassay, serum cytokine and chemokine profiles were assayed among participants without an adenoma (n = 97) and those with an adenoma (n = 97) enrolled in the NCI-funded Insulin Resistance Atherosclerosis Colon Study. The concentrations of interleukin-10 (IL-10), IL-1ß, IL-6, IL-17A, IL-2, IL-4, IL-7, IL-12(p70), interferon-γ (IFN-γ), macrophage chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), granulocyte macrophage colony-stimulating factor (GM-CSF), and macrophage inflammatory protein-1ß (MIP-1ß) were determined. Multiple logistic regression analyses were used to evaluate the association between adenoma prevalence and cytokine levels. RESULTS: The presence of colorectal adenomas was not associated with significant increases in the systemic levels of proinflammatory (TNF-α, IL-6, IL-1ß) or T-cell polarizing (IL-12, IL-2, IL-10, IL-4, IL-17, IFN-γ) cytokines. Furthermore, MCP-1 and RANTES levels were equivalent in the serum of study participants with and without adenomas. CONCLUSIONS: These findings suggest colorectal adenoma prevalence may not be associated with significant alterations in systemic inflammation.

Body fatness as a cause of cancer: epidemiologic clues to biologic mechanisms.

Carrying excess body fat is a leading cause of cancer. Epidemiologic evidence gives strong clues about the mechanisms that link excess adiposity to risk for several cancer sites. For postmenopausal breast cancer and endometrial cancer, the hyper-estrogenic state that is induced by excess body fatness is the likely cause. For esophageal cancer and gallbladder cancer, chronic local inflammation induced by acid reflux and gallstones is the likely cause, and for liver cancer, local inflammation induced by hepatic fatty infiltration is the likely cause. However, for several other cancers known to be associated with excess adiposity, including cancers of the colon, pancreas, ovary, kidney, and prostate, specific causes are not known. Possible candidates include elevated systemic or local tissue inflammation induced by adiposity and effects of the elevated levels of leptin, insulin, IGFs, and depressed immune function that are seen with excess adiposity. There is growing evidence that intentional weight loss not only reduces circulating levels of cancer-associated factors but that it also reduces cancer incidence and recurrence. Better research is needed to understand the mechanisms that link excess body fat to cancer risk as well as to understand the amount of weight loss needed for substantial cancer risk reduction. Finally, as we develop better understanding of the mediators of the effects of excess body fatness on cancer risk, we should identify pharmacologic interventions that target those mediators so that they can be used to complement weight loss in order to reduce cancer risk.

Association between lifetime exposure to inorganic arsenic in drinking water and coronary heart disease in Colorado residents.

BACKGROUND: Chronic diseases, including coronary heart disease (CHD), have been associated with ingestion of drinking water with high levels of inorganic arsenic (> 1,000 µg/L). However, associations have been inconclusive in populations with lower levels (< 100 µg/L) of inorganic arsenic exposure. OBJECTIVES: We conducted a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of CHD. METHODS: This study included 555 participants with 96 CHD events diagnosed between 1984 and 1998 for which individual lifetime arsenic exposure estimates were determined using data from structured interviews and secondary data sources to determine lifetime residence, which was linked to a geospatial model of arsenic concentrations in drinking water. These lifetime arsenic exposure estimates were correlated with historically collected urinary arsenic concentrations. A Cox proportional-hazards model with time-dependent CHD risk factors was used to assess the association between time-weighted average (TWA) lifetime exposure to low-level inorganic arsenic in drinking water and incident CHD. RESULTS: We estimated a positive association between low-level inorganic arsenic exposure and CHD risk [hazard ratio (HR): = 1.38, 95% CI: 1.09, 1.78] per 15 µg/L while adjusting for age, sex, first-degree family history of CHD, and serum low-density lipoprotein levels. The risk of CHD increased monotonically with increasing TWAs for inorganic arsenic exposure in water relative to < 20 µg/L (HR = 1.2, 95% CI: 0.6, 2.2 for 20-30 µg/L; HR = 2.2; 95% CI: 1.2, 4.0 for 30-45 µg/L; and HR = 3, 95% CI: 1.1, 9.1 for 45-88 µg/L). CONCLUSIONS: Lifetime exposure to low-level inorganic arsenic in drinking water was associated with increased risk for CHD in this population.

Colon cancer screening for Colorado's underserved: a community clinic/academic partnership.

BACKGROUND: Colorectal cancer (CRC) is largely preventable by finding and removing adenomas, but many people have not been screened, especially the uninsured with low income. PURPOSE: To establish a statewide infrastructure to ensure that low-income Coloradans receive colonoscopy for CRC screening and diagnostic evaluation. DESIGN: In 2006, a statewide program to provide free colonoscopy to uninsured Coloradans was developed as a partnership between the University of Colorado Cancer Center and Colorado safety-net clinics. Funded by excise tax revenues, the Colorado Colorectal Screening Program (CCSP) successfully embedded screening into primary care, providing patient navigation support and reimbursement that allowed primary care providers to refer patients for colonoscopy. SETTING/PARTICIPANTS: More than 50 safety-net clinics joined the CCSP to provide colonoscopies to uninsured Coloradans with low income, aged ≥50 years or <50 years at elevated risk, lawfully present and needing CRC screening by American Cancer Society consensus guidelines. MAIN OUTCOME MEASURES: Process and clinical outcomes included people screened, show rates, patient satisfaction, and quality measures, such as adenoma detection rate, bowel cleansing quality, and timeliness of care. Program costs and benefits were estimated. The 2013 analysis was completed using 2006-2012 data on 13,252 of 13,774 people receiving colonoscopy. RESULTS: In 2006-2012, the CCSP screened 13,774 people, with 38% minorities and 39% men. Patient navigators ensured >90% of those referred attended their colonoscopy. Adenomas were removed from 27% of patients and 1% had cancers diagnosed. Total direct medical services cost was $998/person receiving colonoscopy. About 325 fewer future incident CRCs were predicted due to adenoma removal, projecting substantial future cost savings. CONCLUSIONS: The CCSP, a successful community clinic/academic partnership provides cost-effective CRC screening and prevention services to low-income uninsured Coloradans and establishes the infrastructure to support screening low-income Coloradans as Affordable Care Act reforms provide payer coverage for them.

Weight gain prior to entry into a weight-loss intervention study among overweight and obese breast cancer survivors.

PURPOSE: Changes in cancer therapy, in addition to changes in obesity prevalence, suggest the need for a current assessment of weight gain patterns following breast cancer diagnosis. The aim of this study was to evaluate factors associated with weight gain among breast cancer survivors prior to enrolling into a behavioral weight loss intervention. METHODS: Anthropometric measures and data on weight-related factors were collected at baseline on 665 breast cancer survivors. Postdiagnosis weight gain was determined between entry into the trial and previous diagnosis up to 5 years. Multivariate logistic regression analyses were used to evaluate the association between weight gain and influencing factors. RESULTS: The mean weight gain was 4.5 % body weight (standard deviation = 10.6); 44 % of women experienced ≥5 % body weight gain. The risk of weight gain was inversely associated with age (adjusted odds ratio (ORadj) = 0.97, 95 % confidence interval (95 % CI) 0.95-0.99), Hispanic ethnicity (ORadj = 0.30, 95 % CI 0.13-0.68), and overweight (ORadj = 0.11, 95 % CI 0.05-0.23) or obese (ORadj = 0.03, 95 % CI 0.02-0.07) status at diagnosis and positively associated with time elapsed since diagnosis (ORadj = 1.19/year, 95 % CI 1.04-1.36). Women prescribed aromatase inhibitors were 46 % less likely to gain weight compared to women prescribed selective estrogen-receptor modulators (ORadj = 0.54, 95 % CI 0.31-0.93). The risk of weight gain was positively associated with smoking at diagnosis (ORadj = 2.69, 95 % CI 1.12-6.49) although this was attributable to women who subsequently quit smoking. CONCLUSIONS: Postdiagnosis weight gain is common and complex and influenced by age, ethnicity, weight, smoking status, time elapsed since diagnosis, and endocrine-modulating therapy. IMPLICATIONS FOR CANCER SURVIVORS: Weight gain continues to be a concern following a diagnosis of breast cancer. Factors influencing this weight gain include age, ethnicity, weight, smoking status, time elapsed since diagnosis, and endocrine-modulating therapy. Effective weight management strategies are needed for this population of women.

Predicting arsenic concentrations in groundwater of San Luis Valley, Colorado: implications for individual-level lifetime exposure assessment.

Consumption of inorganic arsenic in drinking water at high levels has been associated with chronic diseases. Risk is less clear at lower levels of arsenic, in part due to difficulties in estimating exposure. Herein we characterize spatial and temporal variability of arsenic concentrations and develop models for predicting aquifer arsenic concentrations in the San Luis Valley, Colorado, an area of moderately elevated arsenic in groundwater. This study included historical water samples with total arsenic concentrations from 595 unique well locations. A longitudinal analysis established temporal stability in arsenic levels in individual wells. The mean arsenic levels for a random sample of 535 wells were incorporated into five kriging models to predict groundwater arsenic concentrations at any point in time. A separate validation dataset (n = 60 wells) was used to identify the model with strongest predictability. Findings indicate that arsenic concentrations are temporally stable (r = 0.88; 95 % CI 0.83-0.92 for samples collected from the same well 15-25 years apart) and the spatial model created using ordinary kriging best predicted arsenic concentrations (ρ = 0.72 between predicted and observed validation data). These findings illustrate the value of geostatistical modeling of arsenic and suggest the San Luis Valley is a good region for conducting epidemiologic studies of groundwater metals because of the ability to accurately predict variation in groundwater arsenic concentrations.