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.

The Imperative for Population-based Cancer Registration of All Metastatic Cancers.

Metastases are the main cause of morbidity and mortality from solid tumors. Surprisingly, population-based cancer registries in various countries, including the National Cancer Institute's Surveillance, Epidemiology, and End Results program in the United States, only capture data on individuals diagnosed with cancers that are metastatic at diagnosis (M1). Metastatic recurrences of previously diagnosed, initially nonmetastatic tumors are missed. Devasia and colleagues specify an illness-death model for chronic disease and estimate that in prostate cancer, which has a large pool of primary disease that may or may not progress to metastases, about half of all metastatic cancers arise as recurrences from initially nonmetastatic disease. Capturing all incident metastatic cancer cases across all tumor types in population-based cancer registries, not only based on initial stage at diagnosis, would be critical to better understand the disparities in metastatic disease burden and the effectiveness of primary prevention, screening, and therapies for primary and metastatic disease. See related article by Devasia et al., p. 659.

Impact of neighborhood socioeconomic status, income segregation, and greenness on blood biomarkers of inflammation.

BACKGROUND: Neighborhood deprivation is linked with inflammation, which may explain poorer health across populations. Behavioral risk factors are assumed to largely mediate these relationships, but few studies have examined this. We examined three neighborhood contextual factors that could exert direct effects on inflammation: (1) neighborhood socioeconomic status, (2) an index of concentration at extremes (that measures segregation), and (3) surrounding vegetation (greenness). METHODS: Using blood samples and addresses collected from prospective cohorts of 7,930 male (1990-1994) and 16,183 female (1986-1990) health professionals with at least one inflammatory marker, we prospectively linked neighborhood contextual factors to inflammatory biomarkers (adiponectin, C-reactive protein, interleukin-6, soluble tumor necrosis factor receptor-2). Log-transformed, z-scaled component measures were used to calculate an inflammation score. Neighborhood socioeconomic status and index of concentration of extremes were obtained from the 1990 decennial census and linked to participant addresses. Surrounding greenness was assessed from satellite data and focal statistics were applied to generate exposures within 270 m and 1230 m of the participants' address. We fit multiple linear regression models adjusting for demographic, clinical, and behavioral risk factors. RESULTS: Higher neighborhood socioeconomic status was associated with lower inflammation score in women (ß for interquartile range increase = -27.7%, 95% CI: -34.9%, -19.8%) and men (ß = -21.2%, 95% CI: -31.0%, -10.1%). Similarly, participants in neighborhoods with higher concentrations of high-income households were associated with lower inflammation score in women (ß = -27.8%, 95% CI: -35.8%, -18.7%) and men (ß = -16.4%, 95% CI: -29.7%, -0.56%). Surrounding greenness within 270 m of each participant's address was associated with lower inflammation score in women (ß = -18.9%, 95% CI: -28.9%, -7.4%) but not men. Results were robust to sensitivity analyses to assess unmeasured confounding and selection bias. DISCUSSION: Our findings support the hypothesis that adverse neighborhood environments may contribute to inflammation through pathways independent of behavioral risk factors, including psychosocial stress and toxic environments.

Exploratory assessment of pineal gland volume, composition, and urinary 6-sulfatoxymelatonin levels on prostate cancer risk.

INTRODUCTION: Melatonin levels are partially driven by the parenchyma volume of the pineal gland. Low urinary levels of 6-sulfatoxymelatonin have been associated with increased risk of advanced prostate cancer, but the relationship between pineal gland volume and composition and prostate cancer risk has not been examined. MATERIALS AND METHODS: We utilized data from 864 men from the AGES-Reykjavik Study with complete pineal gland volumes and urinary 6-sulfatoxymelatonin measurements. Pineal parenchyma, calcification, and cyst volumes were calculated from brain magnetic resonance imaging. Levels of 6-sulfatoxymelatonin were assayed from prediagnostic urine samples. We calculated Pearson correlation coefficients between parenchyma volume and urinary 6-sulfatoxymelatonin levels. We used Cox proportional hazards regression to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) comparing prostate cancer risk across parenchyma volume tertiles and across categories factoring in parenchyma volume, gland composition, and urinary 6-sulfatoxymelatonin level. RESULTS: Parenchyma volume was moderately correlated with urinary 6-sulfatoxymelatonin level (r = .24; p < .01). There was no statistically significant association between parenchyma volume tertile and prostate cancer risk. Men with high parenchyma volume, pineal cysts and calcifications, and low urinary 6-sulfatoxymelatonin levels had almost twice the risk of total prostate cancer as men with low parenchyma volume, no pineal calcifications or cysts, and low urinary 6-sulfatoxymelatonin levels (HR: 1.98; 95% CI: 1.02, 3.84; p: .04). CONCLUSIONS: Although parenchyma volume is not associated with prostate cancer risk, pineal gland composition and other circadian dynamics may influence risk for prostate cancer. Additional studies are needed to examine the interplay of pineal gland volume, composition, and melatonin levels on prostate cancer risk.

Assessment of Time-to-Treatment Initiation and Survival in a Cohort of Patients With Common Cancers.

Importance: Resource limitations because of pandemic or other stresses on infrastructure necessitate the triage of time-sensitive care, including cancer treatments. Optimal time to treatment is underexplored, so recommendations for which cancer treatments can be deferred are often based on expert opinion. Objective: To evaluate the association between increased time to definitive therapy and mortality as a function of cancer type and stage for the 4 most prevalent cancers in the US. Design, Setting, and Participants: This cohort study assessed treatment and outcome information from patients with nonmetastatic breast, prostate, non-small cell lung (NSCLC), and colon cancers from 2004 to 2015, with data analyzed January to March 2020. Data on outcomes associated with appropriate curative-intent surgical, radiation, or medical therapy were gathered from the National Cancer Database. Exposures: Time-to-treatment initiation (TTI), the interval between diagnosis and therapy, using intervals of 8 to 60, 61 to 120, 121 to 180, and greater than 180 days. Main Outcomes and Measures: 5-year and 10-year predicted all-cause mortality. Results: This study included 2 241 706 patients (mean [SD] age 63 [11.9] years, 1 268 794 [56.6%] women, 1 880 317 [83.9%] White): 1 165 585 (52.0%) with breast cancer, 853 030 (38.1%) with prostate cancer, 130 597 (5.8%) with NSCLC, and 92 494 (4.1%) with colon cancer. Median (interquartile range) TTI by cancer was 32 (21-48) days for breast, 79 (55-117) days for prostate, 41 (27-62) days for NSCLC, and 26 (16-40) days for colon. Across all cancers, a general increase in the 5-year and 10-year predicted mortality was associated with increasing TTI. The most pronounced mortality association was for colon cancer (eg, 5 y predicted mortality, stage III: TTI 61-120 d, 38.9% vs. 181-365 d, 47.8%), followed by stage I NSCLC (5 y predicted mortality: TTI 61-120 d, 47.4% vs 181-365 d, 47.6%), while survival for prostate cancer was least associated (eg, 5 y predicted mortality, high risk: TTI 61-120 d, 12.8% vs 181-365 d, 14.1%), followed by breast cancer (eg, 5 y predicted mortality, stage I: TTI 61-120 d, 11.0% vs. 181-365 d, 15.2%). A nonsignificant difference in treatment delays and worsened survival was observed for stage II lung cancer patients-who had the highest all-cause mortality for any TTI regardless of treatment timing. Conclusions and Relevance: In this cohort study, for all studied cancers there was evidence that shorter TTI was associated with lower mortality, suggesting an indirect association between treatment deferral and mortality that may not become evident for years. In contrast to current pandemic-related guidelines, these findings support more timely definitive treatment for intermediate-risk and high-risk prostate cancer.

Risk of dementia following androgen deprivation therapy for treatment of prostate cancer.

BACKGROUND: Evidence for androgen deprivation therapy (ADT) and risk of dementia is both limited and mixed. We aimed to assess the association between ADT and risk of dementia among men with localized and locally advanced prostate cancer (PCa). METHODS: We conducted a retrospective cohort study using SEER-Medicare-linked data among 100,414 men aged ≥ 66 years and diagnosed with localized and locally advanced PCa (cT1-cT4) between 1992 and 2009. We excluded men with a history of stroke, dementia, or use of psychiatric services. Men were followed until death or administrative end of follow-up at 36 months. Inverse-probability weighted Fine-Gray models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for Alzheimer's, all-cause dementia, and use of psychiatric services by duration of pharmacologic ADT (0, 1-6, and ≥ 7 months). RESULTS: Among 100,414 men with PCa (median age 73 [IQR: 69-77] years; 84% white, 10% black), 38% (n = 37,911) received ADT within 6 months of diagnosis. Receipt of any pharmacologic ADT was associated with a 17% higher risk of all-cause dementia (HR 1.17, 95% CI 1.07-1.27), 23% higher risk of Alzheimer's (HR 1.23, 95% CI 1.11-1.37), and 10% higher risk of psychiatric services use, though the confidence interval included the null (HR 1.10, 95% CI 1.00-1.22). Longer duration of ADT (≥7 months) was associated with a 25% higher risk of all-cause dementia, 34% higher risk of Alzheimer's, and 9% higher risk of psychiatric services, compared with no ADT. CONCLUSIONS: Our study supports an association between pharmacologic ADT and higher risk of all-cause dementia, Alzheimer's, and use of psychiatric services among men with localized and locally advanced PCa.

Relation between tobacco control policies and population at high risk of lung cancer in the European Union.

INTRODUCTION: Lung cancer accounts for nearly 2 million deaths per year worldwide, the majority of cases due to smoking as the main risk factor associated. The aim of this study was to assess the relation between the level of implementation of tobacco control policies and the population at high risk of lung cancer in the European Union (EU). METHODS: The Special Eurobarometer 458 "Attitudes of Europeans towards tobacco and electronic cigarettes", conducted in 2017, and the Tobacco Control Scale (TCS) 2010, 2013, and 2016 were the sources of our data. High risk of lung cancer was defined by the inclusion criteria in the National Lung Screening Trial (NLST) and the Dutch-Belgian Lung Cancer Screening Trial (NELSON), the largest lung cancer screening trials carried out in the US and the EU. We calculated Spearman's rank correlation coefficients (rsp) and fitted multilevel generalized linear mixed models using the quasi-Poisson family to assess the correlation at the national level and analyze the association at the individual level, respectively, between the scores in the TCS (higher scores means better implementation of tobacco control policies) and the proportion of individuals at high risk of lung cancer in member states of the EU. RESULTS: The scores in the TCS 2010 were statistically negatively correlated with the current proportion of ever and former smokers at high risk according to NELSON criteria (-0.41; 95%CI -0.68, -0.04 and -0.49; 95%CI -0.73, -0.13, respectively). We observed statistically significant inverse associations between the scores in the TCS 2010 for the highest quartiles and the proportion of individuals at high risk of lung cancer according to both criteria. Non-statistically significant negative correlations and inverse associations were observed with other TCS. CONCLUSION: There is a lag between the implementation of tobacco control policies and the reduction of the rates of high risk of lung cancer. Member states should reinforce comprehensive tobacco control policies to reduce the population at high risk of lung cancer in the EU.

The Consortium of Metabolomics Studies (COMETS): Metabolomics in 47 Prospective Cohort Studies.

The Consortium of Metabolomics Studies (COMETS) was established in 2014 to facilitate large-scale collaborative research on the human metabolome and its relationship with disease etiology, diagnosis, and prognosis. COMETS comprises 47 cohorts from Asia, Europe, North America, and South America that together include more than 136,000 participants with blood metabolomics data on samples collected from 1985 to 2017. Metabolomics data were provided by 17 different platforms, with the most frequently used labs being Metabolon, Inc. (14 cohorts), the Broad Institute (15 cohorts), and Nightingale Health (11 cohorts). Participants have been followed for a median of 23 years for health outcomes including death, cancer, cardiovascular disease, diabetes, and others; many of the studies are ongoing. Available exposure-related data include common clinical measurements and behavioral factors, as well as genome-wide genotype data. Two feasibility studies were conducted to evaluate the comparability of metabolomics platforms used by COMETS cohorts. The first study showed that the overlap between any 2 different laboratories ranged from 6 to 121 metabolites at 5 leading laboratories. The second study showed that the median Spearman correlation comparing 111 overlapping metabolites captured by Metabolon and the Broad Institute was 0.79 (interquartile range, 0.56-0.89).

Validity of self-reported health plan information in a population-based health survey.

OBJECTIVE: To validate information on private health insurance coverage in a population-based study. METHODS: Respondents to the Massachusetts Behavioral Risk Factor Surveillance System were asked the name of their health plan company (affiliation) and specific brand of insurance (product), the duration in which they belonged to the plan, and demographic and health-related data. Information on plan affiliation and product was used to classify individuals on type of coverage. At the end of the survey, respondents with health insurance were asked to retrieve their health plan cards, and to read detailed information from the cards. Self-reported data were compared with information from the cards. RESULTS: Self-reported information on health plan affiliation agreed with plan cards for 93 percent of individuals, while agreement was 79 percent for health plan product. Among health maintenance organization (HMO) participants, 93 percent correctly reported being in an HMO (sensitivity), whereas 76 percent of respondents in a non-HMO plan correctly self-reported (specificity). Individuals with higher levels of income, those with a primary care doctor, and those in a health plan for at least 1 year had higher agreement. Higher validity was associated with poor physical health and recent cancer screening. CONCLUSIONS: Self-reported data on health plan affiliation and product have good validity in a population-based sample of adults. While agreement differs according to specific respondent characteristics, these differences do not appear substantial.

Identifying Health Maintenance Organization membership through self-report of health plan name: ascertainment and reliability.

OBJECTIVE: To evaluate the feasibility and reliability of (1) identifying Health Maintenance Organization (HMO) membership by ascertaining self-reported health plan name in a telephone survey and (2) using external information to determine whether the plan was an HMO. METHODS: Respondents to the 1999-2001 Massachusetts Behavioral Risk Factor Surveillance System (BRFSS) and the 1999 Massachusetts Colorectal Cancer (CRC) survey were asked to name their health plan. The authors used information from external sources to classify the plan as an HMO or a non-HMO. Test-retest reliability of reported plan name was examined overall, by demographic characteristics, and by health plan name. Reliability of HMO classification was tested with the kappa statistic. RESULTS: More than 88 percent of respondents with commercial health insurance provided their health plan name; 84 percent reported a plan that could be assigned as either an HMO or a non-HMO. The percentage whose HMO status could be assigned differed by demographic characteristics. Among those assigned, the distribution of specific HMOs among survey respondents was similar to the distribution reported by the Massachusetts Division of Insurance. In a subsample, 78 percent reported the same health plan during a follow-up interview. Agreement was higher for men, and differed according to the plan reported at the first time point. Kappa for HMO classification from health plan name was 0.87. CONCLUSIONS: Self-report of health plan name is a feasible and reliable method to ascertain health insurance information in a telephone interview.

Validity and reliability of self-reported total energy expenditure using a novel instrument.

Improved methods for quantitative self-reports of total physical activity in epidemiological studies are needed. We evaluated randomly selected individuals' ability to integrate their perception of physical activity over time to produce an estimate of the "usual" level, using a novel instrument for self-quantification of energy expenditure. A population-based sample of 418 Swedish men and women, age 20-59, completed a questionnaire containing the new instrument. For validation, three 24 hour recalls by phone served as gold standard. Reproducibility was assessed through administering the instrument another three times. The validation involved 133 subjects and another 160 completed the reproducibility evaluation. Pearson correlation between usual daily energy expenditure measured by the instrument and the mean of the 24 hour recalls was 0.73. After subdividing the self-reported daily energy expenditure and the mean of the 24 hour recalls into quintiles, 83.5% of the participants remained in the same quintile, or one quintile apart. There was a tendency towards overestimation of usual daily physical activity. This was significantly associated with low education. Reproducibility showed an intraclass correlation of 0.55. Although integrated reports of usual daily energy expenditure over longer periods seem to be afflicted with a tendency of overestimation, total energy expenditure can be estimated with reasonable validity and reproducibility using our instrument.

Risk assessment criteria applied to a screening exam: implications for improving the efficiency of a sealant program.

OBJECTIVES: The present study aimed to determine the ability of first-grade screening exam findings to predict carious lesions in permanent first molars by fourth grade. The ability to identify high-risk children would be useful in the rational allocation of limited public health resources, such as the application of sealants. METHODS: Screening exams were performed on 204 children in 1st grade and 4th grade. Analyses were conducted at both the child- and molar- levels. Cross-tabulations were used to identify the threshold dmfs + DMFS in first grade that had the highest sensitivity and highest negative predictive value for discriminating between children with and without permanent caries (1) in the entire population and (2) in subpopulations defined by race/ethnicity, gender, and language spoken at home. This threshold then was entered into logistic regression models. RESULTS: On the child and molar level, the study determined that dmfs + DMFS > 0 had the highest sensitivity (child: 69.4%, molar: 74.7%) and negative predictive value (child: 87.8%, molar: 94.4%). Using this test criterion, univariate logistic regression of the child-level data revealed an odds ratio of 2.72 (p = 0.012) for presence of permanent tooth caries experience. Controlling for gender, grade, race/ethnicity, and language spoken at home, the odds ratio increased slightly to 2.76 (p = 0.012). CONCLUSIONS: There is a relationship between carious lesion experience in 1st grade and carious lesion incidence in the first permanent molars by 4th grade. Using the dmfs + DMFS > 0 criterion may help public health providers determine which children should receive sealants when resources do not allow the delivery of sealants to all children.