Different operationalizations of the 2018 WCRF/AICR cancer prevention recommendations and risk of cancer.

BACKGROUND: The standardized scoring system assessing adherence to the 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations assigns equal weight for each recommendation, thereby giving higher weight to dietary factors collectively (5 points) than adiposity (1 point) and physical activity (1 point). An alternative score assigning equal weights to the adiposity, physical activity, alcohol, and other dietary (composite) recommendations may better predict cancer associations. METHODS: We examined associations between standardized and alternative scores with cancer risk in two US prospective cohorts. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. RESULTS: During 28 years of follow-up, 16,342 incident cancer cases in women and 8729 cases in men occurred. Individuals in the highest versus lowest quintile of the standardized score had a reduced overall cancer risk (women: HR = 0.89, 95% CI: 0.85, 0.94; men: HR = 0.87, 95% CI: 0.81, 0.94). Results were slightly stronger for the alternative score (women: HR = 0.83, 95% CI: 0.79, 0.87; men: HR = 0.81, 95% CI: 0.75, 0.86). Similar patterns were observed for obesity-related, alcohol-related, smoking-related, and digestive system cancers. CONCLUSIONS: Greater adherence to the WCRF/AICR cancer prevention recommendations was associated with lower cancer risk. A score assigning equal weights to the adiposity, physical activity, alcohol, and all remaining diet components yielded stronger associations than the standardized score.

In utero exposure to diethylstilbestrol and blood DNA methylation in adult women: Results from a meta-analysis of two cohort studies.

BACKGROUND: Prenatal exposure to diethylstilbestrol (DES) is associated with several adverse health outcomes. Animal studies have shown associations between prenatal DES exposure and DNA methylation. OBJECTIVE: The aim of this study was to explore blood DNA methylation in women exposed and unexposed to DES in utero. METHODS: Sixty women (40 exposed and 20 unexposed) in the National Cancer Institute's Combined DES Cohort Study and 199 women (99 exposed and 100 unexposed women) in the Sister Study Cohort were included in this analysis. Within each study, robust linear regression models were used to assess associations between DES exposure and blood DNA methylation. Study-specific associations were combined using fixed-effect meta-analysis with inverse variance weights. Our analysis focused on CpG sites located within nine candidate genes identified in animal models. We further explored whether in utero DES exposure was associated with age acceleration. RESULTS: Blood DNA methylation levels at 10 CpG sites in six of the nine candidate genes were statistically significantly associated with prenatal DES exposure (P < 0.05) in this meta-analysis. Genes included EGF, EMB, EGFR, WNT11, FOS, and TGFB1, which are related to cell proliferation and differentiation. The most statistically significant CpG site was cg19830739 in gene EGF, and it was associated with lower methylation levels in women prenatally exposed to DES compared with those not exposed (P < 0.0001; false discovery rate<0.05). The association between prenatal DES exposure in utero and age acceleration was not statistically significant (P = 0.07 for meta-analyzed results). CONCLUSIONS: There are few opportunities to investigate the effects of prenatal DES exposure. These findings suggest that in utero DES exposure may be associated with differential blood DNA methylation levels, which could mediate the increased risk of several adverse health outcomes observed in exposed women. Our findings need further evaluation using larger data sets.

Modeling the relationship between SARS-CoV-2 RNA in wastewater or sludge and COVID-19 cases in three New England regions.

BACKGROUND: We aimed to compare statistical techniques estimating the association between SARS-CoV-2 RNA in untreated wastewater and sludge and reported coronavirus disease 2019 (COVID-19) cases. METHODS: SARS-CoV-2 RNA concentrations (copies/mL) were measured from 24-h composite samples of wastewater in Massachusetts (MA) (daily; 8/19/2020-1/19/2021) and Maine (ME) (weekly; 9/1/2020-3/2/2021) and sludge samples in Connecticut (CT) (daily; 3/1/2020-6/1/2020). We fit linear, generalized additive with a cubic regression spline (GAM), Poisson, and negative binomial models to estimate the association between SARS-CoV-2 RNA concentration and reported COVID-19 cases. RESULTS: The models that fit the data best were linear [adjusted R2=0.85 (MA), 0.16 (CT), 0.63 (ME); root-mean-square error (RMSE)=0.41 (MA), 1.14 (CT), 0.99 (ME)), GAM (adjusted R2=0.86 (MA), 0.16 (CT) 0.65 (ME); RMSE=0.39 (MA), 1.14 (CT), 0.97 (ME)], and Poisson [pseudo R2=0.84 (MA), 0.21 (CT), 0.52 (ME); RMSE=0.39 (MA), 0.67 (CT), 0.79 (ME)]. CONCLUSIONS: Linear, GAM, and Poisson models outperformed negative binomial models when relating SARS-CoV-2 RNA in wastewater or sludge to reported COVID-19 cases.

Associations between diet quality scores and central obesity among adults in Puerto Rico.

BACKGROUND: Adults in Puerto Rico experience an excessive burden of central obesity. It remains unknown which dietary components are more strongly associated with central obesity in this high-risk group. We aimed to evaluate the relationship of the Mediterranean diet (MeDS) and Alternate Healthy Eating Index 2010 (AHEI) with central obesity in the Puerto Rico Assessment of Diet, Lifestyle and Diseases (PRADLAD) cross-sectional study. METHODS: Data from PRADLAD participants (ages 30-75 years) were used (n = 166). Dietary intake was assessed by food frequency questionnaire. The MeDS [nine components; range: 0 (lowest) to 9 (highest observance of a Mediterranean-like diet)] and AHEI [11 components; range: 0 (lowest) to 110 (highest diet quality)] were defined. Daily intake of foods and beverages within each MeDS component was ranked by contribution to total energy intake. Multivariable logistic regression was used to evaluate associations between MeDS and AHEI with central obesity (waist circumference > 102 cm males, > 88 cm females). RESULTS: Mean ± SD MeDS was 4.46 ± 1.77 and AHEI was 60.2 ± 11.1. Traditional foods representative of the MeDS included potatoes, root vegetables, fruit juice, avocados, bread, oatmeal, beans, chicken, seafood, low-fat milk, cheese, eggs and beer. Adjusted odds ratios and 95% confidence intervals of central obesity were 0.78 (0.63-0.97) per unit increment of MeDS and 0.61 (0.42-0.90) per 10-unit increment of AHEI. CONCLUSIONS: Higher adherence to MeDS or AHEI was associated with lower central obesity in adults in Puerto Rico. Consuming traditional foods reflecting these dietary patterns (i.e., Mediterranean-like) may reduce central obesity in high-risk populations.

Lifetime dairy product consumption and breast cancer risk: a prospective cohort study by tumor subtypes.

BACKGROUND: Previous literature on dairy products and risk of breast cancer is inconsistent, and the relationship may depend on the life-period of dietary assessment. OBJECTIVE: We examined dairy consumption from adolescence through later adulthood and incidence of breast cancer by menopausal status and tumor molecular subtypes in the Nurses' Health Study (NHS), a prospective cohort study. METHODS: We analyzed data from 63,847 females in the NHS collected from 1980 to 2018. Average intake of dairy products during adulthood was assessed by validated semiquantitative food frequency questionnaires throughout follow-up. Participants recalled adolescent dietary intake in 1986. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) relating dairy product consumption to breast cancer risk overall, by menopausal status, and by subtypes. RESULTS: We documented 5733 incident cases of invasive breast cancer during 32 y of follow-up (n = 5298 postmenopausal). Lifetime, adolescent, adulthood, and postmenopausal total dairy and milk intakes were not associated with overall breast cancer risk (nonsignificant HRs comparing highest with lowest quintile range = 0.97-1.08), although there was a suggestive positive association between adolescent milk intake and breast cancer risk (HR: 1.09; 95% CI: 1.00, 1.18). Higher lifetime and premenopausal cheese intakes were associated with modestly lower risks of breast cancer (comparing highest with lowest quintile, HR for lifetime cheese intake: 0.90; 95% CI: 0.82, 0.98; HR for premenopausal cheese intake: 0.89; 95% CI: 0.79, 1.00). Results varied by tumor subtype and some evidence for heterogeneity was observed for an association between premenopausal milk intake and breast cancer (HR for estrogen receptor [ER]-positive: 0.84; 95% CI: 0.72, 0.99; ER-negative: 1.36; 95% CI: 1.00, 1.84; P heterogeneity = 0.04). CONCLUSIONS: These findings suggest that overall dairy consumption was not associated with risk of breast cancer. However, heterogeneity was observed for type of dairy food, period of life, and tumor subtypes.

Development and application of an evidence-based directed acyclic graph to evaluate the associations between metal mixtures and cardiometabolic outcomes.

Objectives: Specifying causal models to assess relationships among metal mixtures and cardiometabolic outcomes requires evidence-based models of the causal structures; however, such models have not been previously published. The objective of this study was to develop and evaluate a directed acyclic graph (DAG) diagraming metal mixture exposure and cardiometabolic outcomes. Methods: We conducted a literature search to develop the DAG of metal mixtures and cardiometabolic outcomes. To evaluate consistency of the DAG, we tested the suggested conditional independence statements using linear and logistic regression analyses with data from the San Luis Valley Diabetes Study (SLVDS; n=1795). We calculated the proportion of statements supported by the data and compared this to the proportion of conditional independence statements supported by 1,000 DAGs with the same structure but randomly permuted nodes. Next, we used our DAG to identify minimally sufficient adjustment sets needed to estimate the association between metal mixtures and cardiometabolic outcomes (i.e., cardiovascular disease, fasting glucose, and systolic blood pressure). We applied them to the SLVDS using Bayesian kernel machine regression, linear mixed effects, and Cox proportional hazards models. Results: From the 42 articles included in the review, we developed an evidence-based DAG with 74 testable conditional independence statements (43 % supported by SLVDS data). We observed evidence for an association between As and Mn and fasting glucose. Conclusions: We developed, tested, and applied an evidence-based approach to analyze associations between metal mixtures and cardiometabolic health.

Specific Dietary Protein Sources Are Associated with Cardiometabolic Risk Factors in the Boston Puerto Rican Health Study.

BACKGROUND: Puerto Rican adults residing in the US mainland experience a high prevalence of metabolic syndrome (MetS). A diet containing healthy protein-rich sources may help control risk factors for MetS. OBJECTIVE: This study aimed to evaluate 2-year longitudinal associations between intake of various protein-rich foods and changes in the six MetS components. DESIGN: This is a secondary analysis of a longitudinal cohort study using data from the baseline (2004-2007) and 2-year follow-up visits (2006-2011) in the Boston Puerto Rican Health Study. PARTICIPANTS/SETTING: Participants were self-identified Puerto Ricans, aged 45 to 75 years, residing in Boston, Massachusetts, or the surrounding area (n = 1,126). MAIN OUTCOME MEASURES: MetS components were fasting glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, systolic and diastolic blood pressures, and waist circumference. STATISTICAL ANALYSIS: Baseline intake of foods reported in a semiquantitative food frequency questionnaire were expressed as servings/day, and protein-rich foods were categorized as unprocessed white meat, unprocessed red meat, processed meat, milk and yogurt, cheese, fish and seafood, beans, nuts, and eggs. Associations between each continuous protein food group and continuous 2-year change in MetS components were assessed using linear mixed models adjusted for socioeconomic and behavioral factors, and other dietary sources. RESULTS: The top contributors to total protein intake were unprocessed red meat (13.3%) and unprocessed poultry (13.0%), and the lowest were eggs (2.92%) and nuts (0.91%). Higher intake of processed meats was associated with an increase in waist circumference over 2 years (ß = 1.28; standard error [SE] = 0.63), whereas higher intake of fish and seafood was associated with a decrease in waist circumference (ß = -3.47; SE = 1.39). Intake of unprocessed poultry was associated with a decrease in triglycerides (ß = -24.5; SE = 9.13). No other significant associations were observed between protein sources and 2-year changes in MetS components. CONCLUSIONS: Consuming less processed meat and more fish and seafood and unprocessed poultry was associated with decreases in waist circumference and triglycerides among US mainland Puerto Ricans. Other dietary protein sources were not related to cardiometabolic health.

A Longitudinal Study of Exposure to Manganese and Incidence of Metabolic Syndrome.

The association between manganese (Mn) and metabolic syndrome (MetS) is unclear, and no prior study has studied this association longitudinally. The aim of this study was to assess longitudinal associations of Mn exposure with MetS and metabolic outcomes. We used data from the San Luis Valley Diabetes Study (SLVDS), a prospective cohort from rural Colorado with data collected from 1984−1998 (n = 1478). Urinary Mn was measured at baseline (range = 0.20−42.5 µg/L). We assessed the shape of the cross-sectional association between Mn and MetS accounting for effect modification by other metals at baseline using Bayesian kernel machine regression. We assessed longitudinal associations between baseline quartiles of Mn and incident MetS using Fine and Gray competing risks regression models (competing risk = mortality) and between quartiles of Mn and metabolic outcomes using linear mixed effects models. We did not observe evidence that quartiles of Mn were associated with incident MetS (p-value for trend = 0.52). Quartiles of Mn were significantly associated with lower fasting glucose (p-value for trend < 0.01). Lead was found to be a possible effect modifier of the association between Mn and incident MetS. Mn was associated with lower fasting glucose in this rural population. Our results support a possible beneficial effect of Mn on diabetic markers.

Multipollutant, longitudinal analysis of the association between urinary tungsten and incident diabetes in a rural population.

BACKGROUND: Cross-sectional studies suggest tungsten (W) exposure may be associated with diabetes. We assessed longitudinal associations between urinary W and fasting glucose, 2-hour glucose, insulin resistance (HOMA-IR), ß-cell function (HOMA-ß), and incident type 2 diabetes. METHODS: We used data from 1,609 Hispanic and non-Hispanic White adults with 20 to 74 years of age residing in rural Colorado and participating in the San Luis Valley Diabetes Study. Urinary metal exposure values were measured at baseline and natural log-transformed. We assessed longitudinal associations between urinary W and continuous outcome measures using linear-mixed effect models and associations with incident diabetes using Fine and Gray competing risks regression models (competing event = all-cause mortality). The main adjustment set of covariates included: age, sex, ethnicity, education, smoking status, hypertension, body mass index, caloric intake, alcohol intake, and urinary creatinine levels. Secondary models were further adjusted for arsenic, cadmium, and lead exposures. We assessed whether sex or ethnicity were effect modifiers. RESULTS: At baseline, the median W concentration was 0.22 µg/L (interquartile range = 0.20, 0.59). In the main cross-sectional analyses, lnW levels were significantly associated with 3% higher lnHOMA-IR (95% CI = 1 to 5). In the main longitudinal models, lnW was significantly associated with 1% higher natural log-transformed fasting glucose (95% CI = <1 to 1), 3% higher natural log-transformed HOMA-IR (95% CI = 2 to 5), and 28% higher incident diabetes (subdistribution hazard ratio=1.28, 95% CI = 1.09 to 1.50). Results remained significant when further adjusting for other metals. We observed evidence for effect modification by sex and ethnicity. CONCLUSION: Urinary W was longitudinally associated with adverse metabolic health indicators.

Dysfunctional Eating Behaviors and Dietary Intake in Puerto Rico.

Dysfunctional eating behaviors (DEB: emotional eating (EE), uncontrolled eating (UE) and cognitive restraint (CR)) are prevalent in U.S. Latinos and may influence diet. However, this has not been studied in Puerto Rico (PR). This study documents DEB in PR, and explores associations with diet. Cross-sectional study of adults (n = 92) in Ponce, PR. DEB were measured with the TFEQ-R18-V2. The Block Fat and Fruits and Vegetables Screener measured dietary intake. Analysis included adjusted proportions, means and linear regressions. 76%, 88%, and 87% of participants experienced EE, UE and CR, respectively. EE was associated with calories from fats (ß = 1.95, 95% CI 0.40, 3.51) and saturated fats (ß = 3.26, 95% CI 0.67, 5.85), and CR with fruits and vegetables (ß = 0.69, 95% CI 0.20, 1.19). A large percentage of the sample experienced DEB. EE and CR were associated with dietary intake. Studies are needed to understand associations between DEB, diet and health in PR.