Change in Neighborhood Socioeconomic Status and Weight Gain: Dallas Heart Study.

INTRODUCTION: Despite a proposed connection between neighborhood environment and obesity, few longitudinal studies have examined the relationship between change in neighborhood socioeconomic deprivation, as defined by moving between neighborhoods, and change in body weight. The purpose of this study is to examine the longitudinal relationship between moving to more socioeconomically deprived neighborhoods and weight gain as a cardiovascular risk factor. METHODS: Weight (kilograms) was measured in the Dallas Heart Study (DHS), a multiethnic cohort aged 18-65 years, at baseline (2000-2002) and 7-year follow-up (2007-2009, N=1,835). Data were analyzed in 2013-2014. Geocoded addresses were linked to Dallas County, TX, census block groups. A block group-level neighborhood deprivation index (NDI) was created. Multilevel difference-in-difference models with random effects and a Heckman correction factor (HCF) determined weight change relative to NDI change. RESULTS: Forty-nine percent of the DHS population moved (263 to higher NDI, 586 to lower NDI, 47 within same NDI), with blacks more likely to move than whites or Hispanics (p<0.01), but similar baseline BMI and waist circumference were observed in movers versus non-movers (p>0.05). Adjusting for HCF, sex, race, and time-varying covariates, those who moved to areas of higher NDI gained more weight compared to those remaining in the same or moving to a lower NDI (0.64 kg per 1-unit NDI increase, 95% CI=0.09, 1.19). Impact of NDI change on weight gain increased with time (p=0.03). CONCLUSIONS: Moving to more-socioeconomically deprived neighborhoods was associated with weight gain among DHS participants.

Self-Reported Versus Accelerometer-Measured Physical Activity and Biomarkers Among NHANES Youth.

BACKGROUND: Discrepancies in self-report and accelerometer-measured moderate-to-vigorous physical activity (MVPA) may influence relationships with obesity-related biomarkers in youth. METHODS: Data came from 2003-2006 National Health and Nutrition Examination Surveys (NHANES) for 2174 youth ages 12 to 19. Biomarkers were: body mass index (BMI, kg/m2), BMI percentile, height and waist circumference (WC, cm), triceps and subscapular skinfolds (mm), systolic & diastolic blood pressure (BP, mmHg), high-density lipoprotein (HDL, mg/dL), total cholesterol (mg/dL), triglycerides (mg/dL), insulin (µU/ml), C-reactive protein (mg/dL), and glycohemoglobin (%). In separate sex-stratified models, each biomarker was regressed on accelerometer variables [mean MVPA (min/day), nonsedentary counts, and MVPA bouts (mean min/day)] and self-reported MVPA. Covariates were age, race/ethnicity, SES, physical limitations, and asthma. RESULTS: In boys, correlations between self-report and accelerometer MVPA were stronger (boys: r = 0.14-0.21; girls: r = 0.07-0.11; P < .010) and there were significant associations with BMI, WC, triceps skinfold, and SBP and accelerometer MVPA (P < .01). In girls, there were no significant associations between biomarkers and any measures of physical activity. CONCLUSIONS: Physical activity measures should be selected based on the outcome of interest and study population; however, associations between PA and these biomarkers appear to be weak regardless of the measure used.

Risk factors for self-reported arm lymphedema among female breast cancer survivors: a prospective cohort study.

INTRODUCTION: Lymphedema is a potentially debilitating condition that occurs among breast cancer survivors. This study examines the incidence of self-reported lymphedema, timing of lymphedema onset, and associations between sociodemographic, clinical and lifestyle factors and lymphedema risk across racial-ethnic groups using data from a multicenter, multiethnic prospective cohort study of breast cancer survivors, the Health, Eating, Activity and Lifestyle Study. METHODS: A total of 666 women diagnosed with breast cancer staged as in situ, localized or regional disease at ages 35 to 64 years were recruited through the Surveillance, Epidemiology, and End Results registries in New Mexico (non-Hispanic white and Hispanic white), Los Angeles County (black), and Western Washington (non-Hispanic white) and followed for a median of 10.2 years. We evaluated sociodemographic factors, breast cancer- and treatment-related factors, comorbidities, body mass index (BMI), hormonal factors, and lifestyle factors in relation to self-reported lymphedema by fitting Cox proportional hazards models, estimating hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Over the follow-up period, 190 women (29%) reported lymphedema. The median time from breast cancer diagnosis to onset of lymphedema was 10.5 months (range: 0.5 to 134.9 months). Factors independently associated with lymphedema were total/modified radical mastectomy (versus partial/less than total mastectomy; HR = 1.37, 95% CI: 1.01 to 1.85), chemotherapy (versus no chemotherapy; HR = 1.48, 95% CI: 1.09 to 2.02), no lymph nodes removed (versus ≥10 lymph nodes removed; HR = 0.17, 95% CI: 0.08 to 0.33), pre-diagnostic BMI ≥30 kg/m2 (versus BMI <25 kg/m2; HR = 1.59, 95% CI: 1.09 to 2.31), and hypertension (versus no hypertension; HR = 1.49, 95% CI: 1.06 to 2.10). After adjusting for demographics and breast cancer- and treatment-related factors, no significant difference in lymphedema risk was observed across racial/ethnic groups. Analyses stratified by race/ethnicity showed that hypertension and chemotherapy were lymphedema risk factors only for black women. CONCLUSIONS: Breast cancer patients who have undergone extensive surgery or extensive lymph node dissection, or who have a higher BMI should be closely monitored for detection and treatment of lymphedema. Further studies are needed to understand the roles of chemotherapy and hypertension in the development of lymphedema.

Central adiposity after breast cancer diagnosis is related to mortality in the Health, Eating, Activity, and Lifestyle study.

We examined whether waist circumference (WC) and waist-to-hip ratio (WHR) after breast cancer diagnosis are associated with all-cause or breast cancer-specific mortality and explored potential biological pathways mediating these relationships. Our analysis included 621 women diagnosed with local or regional breast cancer who participated in the Health, Eating, Activity, and Lifestyle study. At 30 (±4) months postdiagnosis, trained staff measured participants' waist and hip circumferences and obtained fasting serum samples for biomarker assays for assays of insulin, glucose, C-peptide, insulin growth factor-1 and binding protein-3, C-reactive protein (CRP), and adiponectin. We estimated multivariate hazard ratios (HR) and 95 % confidence intervals (CI) for death over ~9.5 years of follow-up. After adjustment for measured body mass index, treatment, comorbidities, race/ethnicity, diet quality, and postdiagnosis physical activity, WC was positively associated with all-cause mortality (HRq4:q1: 2.99, 95 % CI 1.14, 7.86) but its positive association with breast cancer-specific mortality was not statistically significant (HRq4:q1: 2.69, 95 % CI 0.69, 12.01). WHR was positively associated with all-cause mortality (HRq4:q1: 2.10, 95 % CI 1.08, 4.05) and breast cancer-specific mortality (HRq4:q1: 4.02, 95 % CI 1.31, 12.31). After adjustment for homeostatic model assessment (HOMA) score and C-reactive protein, risk estimates were attenuated and not statistically significant. In this diverse breast cancer survivor cohort, postdiagnosis WC and WHR were associated with all-cause mortality. Insulin resistance and inflammation may mediate the effects of central adiposity on mortality among breast cancer patients.

Comparing indices of diet quality with chronic disease mortality risk in postmenopausal women in the Women's Health Initiative Observational Study: evidence to inform national dietary guidance.

Poor diet quality is thought to be a leading risk factor for years of life lost. We examined how scores on 4 commonly used diet quality indices-the Healthy Eating Index 2010 (HEI), the Alternative Healthy Eating Index 2010 (AHEI), the Alternate Mediterranean Diet (aMED), and the Dietary Approaches to Stop Hypertension (DASH)-are related to the risks of death from all causes, cardiovascular disease (CVD), and cancer among postmenopausal women. Our prospective cohort study included 63,805 participants in the Women's Health Initiative Observational Study (from 1993-2010) who completed a food frequency questionnaire at enrollment. Cox proportional hazards models were fit using person-years as the underlying time metric. We estimated multivariate hazard ratios and 95% confidence intervals for death associated with increasing quintiles of diet quality index scores. During 12.9 years of follow-up, 5,692 deaths occurred, including 1,483 from CVD and 2,384 from cancer. Across indices and after adjustment for multiple covariates, having better diet quality (as assessed by HEI, AHEI, aMED, and DASH scores) was associated with statistically significant 18%-26% lower all-cause and CVD mortality risk. Higher HEI, aMED, and DASH (but not AHEI) scores were associated with a statistically significant 20%-23% lower risk of cancer death. These results suggest that postmenopausal women consuming a diet in line with a priori diet quality indices have a lower risk of death from chronic disease.

Association between class III obesity (BMI of 40-59 kg/m2) and mortality: a pooled analysis of 20 prospective studies.

BACKGROUND: The prevalence of class III obesity (body mass index [BMI]≥40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity. METHODS AND FINDINGS: In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19-83 y at baseline, classified as obese class III (BMI 40.0-59.9 kg/m2) compared with those classified as normal weight (BMI 18.5-24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976-2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40-44.9, 45-49.9, 50-54.9, and 55-59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7-7.3), 8.9 (95% CI: 7.4-10.4), 9.8 (95% CI: 7.4-12.2), and 13.7 (95% CI: 10.5-16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report. CONCLUSIONS: Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight. Please see later in the article for the Editors' Summary.

Better postdiagnosis diet quality is associated with less cancer-related fatigue in breast cancer survivors.

PURPOSE: A comprehensive understanding of the role of modifiable health behaviors in effective management of cancer-related fatigue is needed. Among breast cancer survivors, we examined how postdiagnosis diet quality, independently and jointly with physical activity, is related to fatigue, and the potential mediating role of inflammation. METHODS: Seven hundred seventy women diagnosed with stage 0-IIIA breast cancer in the Health, Eating, Activity, and Lifestyle study completed food frequency and physical activity questionnaires 30 months postdiagnosis. We scored diet quality using the Healthy Eating Index 2010 (HEI-2010). Serum concentrations of C-reactive protein (CRP) were measured in fasting 30-ml blood samples. Multidimensional fatigue was measured 41 months postdiagnosis using the 22-item revised Piper Fatigue Scale. In multivariate linear models, we determined whether fatigue was associated HEI-2010 quartiles (Q1-Q4), and a variable jointly reflecting HEI quartiles and physical activity levels. RESULTS: Survivors with better-quality diets (Q4 vs. Q1) had lower total fatigue (4.1 vs. 4.8, p-contrast = 0.003) and subscale scores (behavioral severity 3.4 vs. 4.2, p-contrast = 0.003; affective meaning 3.9 vs. 4.8, p-contrast = 0.007; sensory 4.4 vs. 5.2, p-contrast = 0.003; cognitive 4.6 vs. 5.0, p-contrast = 0.046). Least squares estimates of fatigue were similar in models including CRP. Compared to survivors with poor-quality diets and no physical activity, survivors with better-quality diets and meeting physical activity recommendations had significantly lower behavioral severity (3.2 vs. 4.7, p-contrast = 0.002) and sensory (3.8 vs. 4.8. p-contrast = 0.006) fatigue scores. CONCLUSION: In this large breast cancer survivor cohort, postdiagnosis diet quality was inversely and independently associated with fatigue. IMPLICATIONS FOR CANCER SURVIVORS: Future interventions designed to improve multiple energy balance behaviors can provide insight into their associations with fatigue.

Neighborhood-level socioeconomic deprivation predicts weight gain in a multi-ethnic population: longitudinal data from the Dallas Heart Study.

OBJECTIVE: The aim of this study is to examine a relationship between neighborhood-level socioeconomic deprivation and weight change in a multi-ethnic cohort from Dallas County, Texas and whether behavioral/psychosocial factors attenuate the relationship. METHODS: Non-movers (those in the same neighborhood throughout the study period) aged 18-65 (N=939) in Dallas Heart Study (DHS) underwent weight measurements between 2000 and 2009 (median 7-year follow-up). Geocoded home addresses defined block groups; a neighborhood deprivation index (NDI) was created (higher NDI=greater deprivation). Multi-level modeling determined weight change relative to NDI. Model fit improvement was examined with adding physical activity and neighborhood environment perceptions (higher score=more unfavorable perceptions) as covariates. A significant interaction between residence length and NDI was found (p-interaction=0.04); results were stratified by median residence length (11 years). RESULTS: Adjusting for age, sex, race/ethnicity, smoking, and education/income, those who lived in neighborhood >11 years gained 1.0 kg per one-unit increment of NDI (p=0.03), or 6 kg for those in highest NDI tertile compared with those in the lowest tertile. Physical activity improved model fit; NDI remained associated with weight gain after adjustment for physical activity and neighborhood environment perceptions. There was no significant relationship between NDI and weight change for those in their neighborhood ≤11 years. CONCLUSIONS: Living in more socioeconomically deprived neighborhoods over a longer time period was associated with weight gain in DHS.

Change in peripheral blood leukocyte telomere length and mortality in breast cancer survivors.

BACKGROUND: Progressive telomere shortening with cell division is a hallmark of aging. Short telomeres are associated with increased cancer risk, but there are conflicting reports about telomere length and mortality in breast cancer survivors. METHODS: We measured peripheral blood leukocyte telomere length at two time points in women enrolled in a multiethnic, prospective cohort of stage I to stage IIIA breast cancer survivors diagnosed between 1995 and 1999 with a median follow-up of 11.2 years. We evaluated associations between telomere length measured at mean 6 (baseline; LTL0; n = 611) and 30 months (LTL30; n = 478) after diagnosis and the change between those time points (n = 478), with breast cancer-specific and all-cause mortality using Cox proportional hazards models adjusted for possible confounders. Statistical tests were two-sided. RESULTS: There were 135 deaths, of which 74 were due to breast cancer. Neither baseline nor 30-month telomere length was associated with either all-cause or breast cancer-specific mortality (LTL0: hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.67 to 1.02; HR = 0.88; 95% CI = 0.67 to 1.15; LTL30: HR = 0.78, 95% CI = 0.59 to 1.05; HR = 0.86; 95% = CI = 0.58 to 1.26, respectively). However, participants whose telomeres shortened between baseline and 30 months were at a statistically significantly increased risk of breast cancer-specific (HR = 3.03; 95% CI = 1.11 to 8.18) and all-cause mortality (HR = 2.38; 95% CI = 1.28 to 4.39) compared with participants whose telomeres lengthened. When follow-up was censored at 5-years after diagnosis, LTL0 (HR = 0.66; 95% CI = 0.45 to 0.96), LTL30 (HR = 0.51; 95% CI = 0.29 to 0.92), and change in telomere length (HR = 3.45; 95% CI = 1.11 to 10.75) were statistically significantly associated with all-cause mortality. CONCLUSIONS: Telomere shortening was associated with increased risk of breast cancer-specific and all-cause mortality, suggesting that change in blood telomere length over time could be a biomarker of prognosis. Research on determinants of telomere length and change is needed.

Better postdiagnosis diet quality is associated with reduced risk of death among postmenopausal women with invasive breast cancer in the women's health initiative.

BACKGROUND: Few studies have evaluated whether adherence to dietary recommendations is associated with mortality among cancer survivors. In breast cancer survivors, we examined how postdiagnosis Healthy Eating Index (HEI)-2005 scores were associated with all-cause and cause-specific mortality. METHODS: Our prospective cohort study included 2,317 postmenopausal women, ages 50 to 79 years, in the Women's Health Initiative's Dietary Modification Trial (n = 1,205) and Observational Study (n = 1,112), who were diagnosed with invasive breast cancer and completed a food frequency questionnaire after being diagnosed. We followed women from this assessment forward. We used Cox proportional hazards models to estimate multivariate-adjusted HRs and 95% confidence intervals (CI) for death from any cause, breast cancer, and causes other than breast cancer, according to HEI-2005 quintiles. RESULTS: Over 9.6 years, 415 deaths occurred. After adjustment for key covariates, women consuming better quality diets had a 26% lower risk of death from any cause (HRQ4:Q1, 0.74; 95% CI, 0.55-0.99; Ptrend = 0.043) and a 42% lower risk of death from non-breast cancer causes (HRQ4:Q1, 0.58; 95% CI, 0.38-0.87; Ptrend = 0.011). HEI-2005 score was not associated with breast cancer death (HRQ4:Q1, 0.91; 95% CI, 0.60-1.40; Ptrend = 0.627). In analyses stratified by tumor estrogen receptor (ER) status, better diet quality was associated with a reduced risk of all-cause mortality among women with ER(+) tumors (n = 1,758; HRQ4:Q1, 0.55; 95% CI, 0.38-0.79; Ptrend = 0.0009). CONCLUSION: Better postdiagnosis diet quality was associated with reduced risk of death, particularly from non-breast cancer causes. IMPACT: Breast cancer survivors may experience improved survival by adhering to U.S. dietary guidelines.

Urban sprawl, obesity, and cancer mortality in the United States: cross-sectional analysis and methodological challenges.

BACKGROUND: Urban sprawl has the potential to influence cancer mortality via direct and indirect effects on obesity, access to health services, physical activity, transportation choices and other correlates of sprawl and urbanization. METHODS: This paper presents a cross-sectional analysis of associations between urban sprawl and cancer mortality in urban and suburban counties of the United States. This ecological analysis was designed to examine whether urban sprawl is associated with total and obesity-related cancer mortality and to what extent these associations differed in different regions of the US. A major focus of our analyses was to adequately account for spatial heterogeneity in mortality. Therefore, we fit a series of regression models, stratified by gender, successively testing for the presence of spatial heterogeneity. Our resulting models included county level variables related to race, smoking, obesity, access to health services, insurance status, socioeconomic position, and broad geographic region as well as a measure of urban sprawl and several interactions. Our most complex models also included random effects to account for any county-level spatial autocorrelation that remained unexplained by these variables. RESULTS: Total cancer mortality rates were higher in less sprawling areas and contrary to our initial hypothesis; this was also true of obesity related cancers in six of seven U.S. regions (census divisions) where there were statistically significant associations between the sprawl index and mortality. We also found significant interactions (p < 0.05) between region and urban sprawl for total and obesity related cancer mortality in both sexes. Thus, the association between urban sprawl and cancer mortality differs in different regions of the US. CONCLUSIONS: Despite higher levels of obesity in more sprawling counties in the US, mortality from obesity related cancer was not greater in such counties. Identification of disparities in cancer mortality within and between geographic regions is an ongoing public health challenge and an opportunity for further analytical work identifying potential causes of these disparities. Future analyses of urban sprawl and health outcomes should consider exploring regional and international variation in associations between sprawl and health.

Organization of primary care practice for providing energy balance care.

PURPOSE: Primary care physicians (PCPs) may not adequately counsel or monitor patients regarding diet, physical activity, and weight control (i.e., provide energy balance care). We assessed the organization of PCPs' practices for providing this care. DESIGN: The study design was a nationally representative survey conducted in 2008. SETTING: The study setting was U.S. primary care practices. SUBJECTS: A total of 1740 PCPs completed two sequential questionnaires (response rate, 55.5%). MEASURES: The study measured PCPs' reports of practice resources, and the frequency of body mass index assessment, counseling, referral for further evaluation/management, and monitoring of patients for energy balance care. ANALYSIS: Descriptive statistics and logistic regression modeling were used. RESULTS: More than 80% of PCPs reported having information resources on diet, physical activity, or weight control available in waiting/exam rooms, but fewer billed (45%), used reminder systems (<30%), or received incentive payments (3%) for energy balance care. A total of 26% reported regularly assessing body mass index and always/often providing counseling as well as tracking patients for progress related to energy balance. In multivariate analyses, PCPs in practices with full electronic health records or those that bill for energy balance care provided this care more often and more comprehensively. There were strong specialty differences, with pediatricians more likely (odds ratio, 1.78; 95% confidence interval, 1.26-2.51) and obstetrician/gynecologists less likely (odds ratio, 0.28; 95% confidence interval, 0.17-0.44) than others to provide energy balance care. CONCLUSION: PCPs' practices are not well organized for providing energy balance care. Further research is needed to understand PCP care-related specialty differences.

Physical activity and cancer-specific mortality in the NIH-AARP Diet and Health Study cohort.

Higher physical activity levels have been associated with a lower risk of developing various cancers and all-cancer mortality, but the impact of pre-diagnosis physical activity on cancer-specific death has not been fully characterized. In the prospective National Institutes of Health-AARP Diet and Health Study with 293,511 men and women, we studied prediagnosis moderate to vigorous intensity leisure time physical activity (MVPA) in the past 10 years and cancer-specific mortality. Over a median 12.1 years, we observed 15,001 cancer deaths. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for MVPA with cancer mortality overall and by 20 specific cancer sites, adjusting for relevant risk factors. Compared to participants reporting never/rare MVPA, those reporting >7 hr/week MVPA had a lower risk of total cancer mortality (HR = 0.89, 95% CI 0.84-0.94; p-trend <0.001). When analyzed by cancer site-specific deaths, comparing those reporting >7 hr/week of MVPA to those reporting never/rare MVPA, we observed a lower risk of death from colon (HR = 0.70; 95% CI 0.57-0.85; p-trend <0.001), liver (0.71; 0.52-0.98; p-trend = 0.012) and lung cancer (0.84; 0.77-0.92; p-trend <0.001) and a significant p-trend for non-Hodgkins lymphoma (0.80; 0.62-1.04; p-trend = 0.017). An unexpected increased mortality p-trend with increasing MVPA was observed for death from kidney cancer (1.42; 0.98-2.03; p-trend = 0.016). Our findings suggest that higher prediagnosis leisure time physical activity is associated with lower risk of overall cancer mortality and mortality from multiple cancer sites. Future studies should confirm observed associations and further explore timing of physical activity and underlying biological mechanisms.

Body mass and weight change in adults in relation to mortality risk.

Using data from the National Institutes of Health-AARP Diet and Health Study, we evaluated the influence of adulthood weight history on mortality risk. The National Institutes of Health-AARP Diet and Health Study is an observational cohort study of US men and women who were aged 50-71 years at entry in 1995-1996. This analysis focused on 109,947 subjects who had never smoked and were younger than age 70 years. We estimated hazard ratios of total and cause-specific mortality for recalled body mass index (BMI; weight (kg)/height (m)(2)) at ages 18, 35, and 50 years; weight change across 3 adult age intervals; and the effect of first attaining an elevated BMI at 4 successive ages. During 12.5 years' follow-up through 2009, 12,017 deaths occurred. BMI at all ages was positively related to mortality. Weight gain was positively related to mortality, with stronger associations for gain between ages 18 and 35 years and ages 35 and 50 years than between ages 50 and 69 years. Mortality risks were higher in persons who attained or exceeded a BMI of 25.0 at a younger age than in persons who reached that threshold later in adulthood, and risks were lowest in persons who maintained a BMI below 25.0. Heavier initial BMI and weight gain in early to middle adulthood strongly predicted mortality risk in persons aged 50-69 years.

Associations between null mutations in GSTT1 and GSTM1, the GSTP1 Ile(105)Val polymorphism, and mortality in breast cancer survivors.

PURPOSE: Here we assessed associations between null mutations in glutathione-S-transferase (GST)T1 and GSTM1 genes, and the rs1695 polymorphism in GSTP1 (Ile(105)Val), and risk of breast cancer-specific (n=45) and all-cause (n=99) mortality in a multiethnic, prospective cohort of 533 women diagnosed with stage I-IIIA breast cancer in 1995-1999, enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study. METHODS: We measured the presence of the null mutation in GSTT1 and GSTM1, and the rs1695 polymorphism in GSTP1 by polymerase chain reaction. We assessed associations between breast-cancer specific and all-cause mortality using Cox proportional hazards models. RESULTS: Participants with ER-negative tumors were more likely to be GSTT1 null (χ(2)=4.52; P=0.03), and African American women were more likely to be GSTM1 null (χ(2)=34.36; P<0.0001). Neither GSTM1 nor GSTT1 null mutations were associated with breast cancer-specific or all-cause mortality. In a model adjusted for body mass index, race/ethnicity, tumor stage and treatment received at diagnosis, the variant Val allele of rs1695 was associated with increased risk of all-cause (HR=1.81, 95% CI 1.16-2.82, P=0.008), but not breast cancer-specific mortality. The GSTT1 null mutation was associated with significantly higher levels of C-reactive protein. CONCLUSIONS: GSTM1 and GSTT1 null genotypes had no effect on outcome; however the variant allele of rs1695 appears to confer increased risk for all-cause mortality in breast-cancer survivors. Given the limited sample size of most studies examining associations between GST polymorphisms with breast cancer survival, and the lack of women undergoing more contemporary treatment protocols (treated prior to 1999), it may be helpful to re-examine this issue among larger samples of women diagnosed after the late 1990s, who all received some form of chemotherapy or radiotherapy.

Disentangling the body weight-bone mineral density association among breast cancer survivors: an examination of the independent roles of lean mass and fat mass.

BACKGROUND: Bone mineral density (BMD) and lean mass (LM) may both decrease in breast cancer survivors, thereby increasing risk of falls and fractures. Research is needed to determine whether lean mass (LM) and fat mass (FM) independently relate to BMD in this patient group. METHODS: The Health, Eating, Activity, and Lifestyle Study participants included 599 women, ages 29-87 years, diagnosed from 1995-1999 with stage 0-IIIA breast cancer, who underwent dual-energy X-ray absorptiometry scans approximately 6-months postdiagnosis. We calculated adjusted geometric means of total body BMD within quartiles (Q) of LM and FM. We also stratified LM-BMD associations by a fat mass index threshold that tracks with obesity (lower body fat: ≤ 12.9 kg/m2; higher body fat: >12.9 kg/m2) and stratified FM-BMD associations by appendicular lean mass index level corresponding with sarcopenia (non-sarcopenic: ≥ 5.45 kg/m2 and sarcopenic: < 5.45 kg/m2). RESULTS: Higher LM (Q4 vs. Q1) was associated with higher total body BMD overall (1.12 g/cm2 vs. 1.07 g/cm2, p-trend < 0.0001), and among survivors with lower body fat (1.13 g/cm2 vs. 1.07 g/cm2, p-trend < 0.0001) and higher body fat (1.15 g/cm2 vs. 1.08 g/cm2, p-trend = 0.004). Higher FM (Q4 vs. Q1) was associated with higher total body BMD overall (1.12 g/cm2 vs. 1.07 g/cm2, p-trend < 0.0001) and among non-sarcopenic survivors (1.15 g/cm2 vs. 1.08 g/cm2, p < 0.0001), but the association was not significant among sarcopenic survivors (1.09 g/cm2 vs. 1.04 g/cm2, p-trend = 0.18). CONCLUSION: Among breast cancer survivors, higher LM and FM were independently related to higher total body BMD. Future exercise interventions to prevent bone loss among survivors should consider the potential relevance of increasing and preserving LM.

The roles of support seeking and race/ethnicity in posttraumatic growth among breast cancer survivors.

Posttraumatic growth (PTG) after cancer can minimize the emotional impact of disease and treatment; however, the facilitators of PTG, including support seeking, are unclear. The authors examined the role of support seeking on PTG among 604 breast cancer survivors ages 40 to 64 from the Health Eating, Activity, and Lifestyle (HEAL) Study. Multivariable linear regression was used to examine predictors of support seeking (participation in support groups and confiding in health care providers) as well as the relationship between support seeking and PTG. Support program participation was moderate (61.1%) compared to the high rates of confiding in health professionals (88.6%), and African Americans were less likely to report participating than non-Hispanic Whites (odds ratio = .14, confidence intervals [0.08, 0.23]). The mean (SD) PTG score was 48.8 (27.4) (range 0-105). Support program participation (ß = 10.4) and confiding in health care providers (ß = 12.9) were associated (p < .001) with higher PTG. In analyses stratified by race/ethnicity, PTG was significantly higher in non-Hispanic Whites and African American support program participants (p < .01), but not significantly higher in Hispanics/Latinas. Confiding in a health care provider was only associated with PTG for non-Hispanic Whites (p = .02). Support program experiences and patient-provider encounters should be examined to determine which attributes facilitate PTG in diverse populations.

Weight, inflammation, cancer-related symptoms and health related quality of life among breast cancer survivors.

Maintaining weight is important for better prognosis of breast cancer survivors. The associations between weight and cancer-related symptoms are not known. We examined associations among weight, weight change, inflammation, cancer-related symptoms, and health-related quality of life (HRQOL) in a cohort of stage 0-IIIA breast cancer survivors. Participants were recruited on average 6 months (2­12 months) after diagnosis. Height, weight, and C-reactive protein (CRP) were assessed at approximately 30 months post-diagnosis; cancer-related symptoms (chest wall and arm symptoms, vasomotor symptoms, urinary incontinence, vaginal symptoms, cognition/mood problems, sleep, sexual interest/function), and HRQOL (SF-36) were assessed at approximately 40 months post-diagnosis. Weight was measured at baseline in a subset. Data on 661 participants were evaluable for body mass index (BMI); 483 were evaluable for weight change. We assessed associations between BMI (<25.0, 25.0­29.9, ≥30.0 kg/m2), post-diagnosis weight change (lost ≥5 %, weight change <5 %, gained ≥5 %), and CRP (tertile) with cancer-related symptoms and HRQOL using analysis of covariance. Higher symptoms scores indicate more frequent or severe symptoms. Higher HRQOL scores indicate better HRQOL. Compared with those with BMI <25 kg/m2, women with BMI ≥30 kg/m2 had the following scores: increased for arm symptoms (+25.0 %), urinary incontinence (+40.0 %), tendency to nap (+18.9 %), and poorer physical functioning (−15.6 %, all p < 0.05). Obese women had lower scores in trouble falling asleep (−9.9 %; p < 0.05). Compared with weight change <5 %, participants with ≥5 % weight gain had lower scores in physical functioning (−7.2 %), role-physical (−15.5 %) and vitality (−11.2 %), and those with weight loss ≥5 % had lower chest wall (−33.0 %) and arm symptom scores (−35.5 %, all p < 0.05). Increasing CRP tertile was associated with worse scores for chest wall symptoms, urinary incontinence, physical functioning, role-physical, vitality and physical component summary scores (all P trend < 0.05). Future studies should examine whether interventions to maintain a healthy weight and reduce inflammation could alleviate cancer-related symptoms and improve HRQOL.