Trends in smoking-attributable and smoking-unrelated lung cancer death rates in the U.S., 1991-2018.

BACKGROUND: In the U.S., lung cancer death rates have declined for decades, primarily due to pronounced decreases in cigarette smoking. However, it is unclear whether there have been similar declines in mortality rates of lung cancer unrelated to smoking. We estimated trends in U.S. lung cancer death rates attributable and not attributable to smoking from 1991-2018. METHODS: The study included 30-79-year-olds in the National Health Interview Survey who were linked to the National Death Index, 1991-2014. Adjusted hazard ratios (HRs) for smoking status and lung cancer death were estimated, and age-specific population attributable fractions (PAFs) were calculated. Annual PAFs were multiplied by annual U.S. national lung cancer mortality, partitioning rates into smoking-attributable and smoking-unrelated lung cancer deaths. All statistical tests were two-sided. RESULTS: During 1991-2018, the proportion of never smokers increased among both men (35.1% to 54.6%) and women (54.0% to 65.4%). Compared to ever smokers, never smokers had 86% lower risk (HR = 0.14; 95%CI 0.12, 0.16) of lung cancer death. The fraction of lung cancer deaths attributable to smoking decreased from 81.4% (95%CI 78.9, 81.4) to 74.7% (95%CI 78.1, 71.4). Smoking-attributable lung cancer death rates declined 2.7%/year (95%CI -2.9, -2.5) and smoking-unrelated lung cancer death rates declined 1.8%/year (95%CI -2.0, -1.5); these declines accelerated in recent years. CONCLUSIONS: An increasing proportion of lung cancer deaths are unrelated to smoking, due to declines in smoking prevalence. However, smoking-unrelated lung cancer death rates have declined, perhaps due to decreases in secondhand smoke and air pollution exposure and treatment improvements.

The 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) score and diabetes risk in the Diabetes Prevention Program Outcomes Study (DPPOS).

BACKGROUND: The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) 3rd expert report highlights up-to-date Cancer Prevention Recommendations that may reduce burdens of many chronic diseases, including diabetes. This study examined if following a lifestyle that aligns with the recommendations - assessed via the 2018 WCRF/AICR Score - was associated with lower risk of type 2 diabetes in high-risk adults participating in the Diabetes Prevention Program Outcomes Study (DPPOS). METHODS: The Diabetes Prevention Program (DPP) randomized adults at high risk for diabetes to receive a lifestyle intervention (ILS), metformin (MET) or a placebo (PLB) (mean: 3.2 years), with additional follow-up in DPPOS for 11 years (mean: 15 years total). 2018 WCRF/AICR Scores included seven components: body weight, physical activity, plant-based foods, fast foods, red and processed meat, sugar-sweetened beverages, and alcohol; the optional breastfeeding component was excluded. Scores ranged 0-7 points (with greater scores indicating greater alignment with the recommendations) and were estimated at years 0, 1, 5, 6, 9, and 15 (N=3,147). Fasting glucose and HbA1c were measured every six months and oral glucose tolerance tests were performed annually. Adjusted Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were used to examine the association of both Score changes from years 0-1 and time-dependent Score changes on diabetes risk through DPP and year 15. RESULTS: Scores improved within all groups over 15 years (p<0.001); ILS Scores improved more than MET or PLB Scores after 1 year (p<0.001). For every 1-unit improvement from years 0-1, there was a 31% and 15% lower diabetes risk in ILS (95% CI: 0.56-0.84) and PLB (95% CI: 0.72-0.97) through DPP, and no significant association in MET. Associations were greatest among American Indian participants, followed by non-Hispanic White and Hispanic participants. Score changes from years 0-1 and time-dependent Score changes in ILS and PLB remained associated with lower risk through year 15. CONCLUSIONS: Score improvements were associated with long-term, lower diabetes risk among high-risk adults randomized to ILS and PLB, but not MET. Future research should explore impact of the Score on cancer risk. TRIAL REGISTRATION: Diabetes Prevention Program: NCT00004992 ; Diabetes Prevention Program Outcomes Study: NCT00038727.

Sex disparities in the incidence of 21 cancer types: Quantification of the contribution of risk factors.

BACKGROUND: Cancer incidence is higher in men than in women at most shared anatomic sites for currently unknown reasons. The authors quantified the extent to which behaviors (smoking and alcohol use), anthropometrics (body mass index and height), lifestyles (physical activity, diet, medications), and medical history collectively explain the male predominance of risk at 21 shared cancer sites. METHODS: Prospective cohort analyses (n = 171,274 male and n = 122,826 female participants; age range, 50-71 years) in the National Institutes of Health-AARP Diet and Health Study (1995-2011). Cancer-specific Cox regression models were used to estimate male-to-female hazard ratios (HRs). The degree to which risk factors explained the observed male-female risk disparity was quantified using the Peters-Belson method. RESULTS: There were 26,693 incident cancers (17,951 in men and 8742 in women). Incidence was significantly lower in men than in women only for thyroid and gallbladder cancers. At most other anatomic sites, the risks were higher in men than in women (adjusted HR range, 1.3-10.8), with the strongest increases for bladder cancer (HR, 3.33; 95% confidence interval [CI], 2.93-3.79), gastric cardia cancer (HR, 3.49; 95% CI, 2.26-5.37), larynx cancer (HR, 3.53; 95% CI, 2.46-5.06), and esophageal adenocarcinoma (HR, 10.80; 95% CI, 7.33-15.90). Risk factors explained a statistically significant (nonzero) proportion of the observed male excess for esophageal adenocarcinoma and cancers of liver, other biliary tract, bladder, skin, colon, rectum, and lung. However, only a modest proportion of the male excess was explained by risk factors (ranging from 50% for lung cancer to 11% for esophageal adenocarcinoma). CONCLUSIONS: Men have a higher risk of cancer than women at most shared anatomic sites. Such male predominance is largely unexplained by risk factors, underscoring a role for sex-related biologic factors.

The 2018 World Cancer Research Fund/American Institute for Cancer Research Score and Cancer Risk: A Longitudinal Analysis in the NIH-AARP Diet and Health Study.

BACKGROUND: We examined associations between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations using the standardized 2018 WCRF/AICR Score and cancer risk among older U.S. adults. METHODS: Participants included 215,102 adults in the NIH-AARP Diet and Health Study followed between 2004 and 2011 (mean 7.0 person-years). Scores (range: 0-7 points) were calculated from self-reported weight, physical activity, and diet and alcohol intake measures. Outcomes included 17 cancers reviewed by WCRF/AICR (cases: male n = 11,066; female n = 8,865) and top three U.S. cancers in males (total n = 4,658; lung n = 2,211; prostate n = 920; colorectal n = 1,527) and females (total n = 5,957; lung n = 1,475; post-menopausal breast n = 3,546; colorectal n = 936). Cox proportional hazard ratios (HRs) were estimated for score and cancer risk associations, stratifying by sex and smoking status. RESULTS: Each one-point score increase was associated with 6% to 13% reduced cancer risk across combined outcomes, except for male never smokers' risk for top three cancers and male current smokers' risk for both combined cancer outcomes. Higher scores were associated with decreased lung cancer risk only among male former smokers (HR, 0.84; 95% CI, 0.79-0.89) and female current smokers (HR, 0.89; 95% CI, 0.82-0.96). Higher scores were associated with 7% to 19% decreased breast cancer risk across smoking strata and 10% to 14% decreased colorectal cancer risk among male and female never and former smokers. CONCLUSIONS: Greater recommendations adherence was associated with reduced cancer risk. IMPACT: Findings emphasize the importance of considering combined contributions of multiple lifestyle factors for cancer prevention among older adults and the potential modifying role of smoking history.

The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score and All-Cause, Cancer, and Cardiovascular Disease Mortality Risk: A Longitudinal Analysis in the NIH-AARP Diet and Health Study.

Background: The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) published Cancer Prevention Recommendations in 2018 focused on modifiable lifestyle factors. Objectives: The aim was to examine how adherence to WCRF/AICR recommendations via the 2018 WCRF/AICR score is associated with risk for all-cause, cancer, and cardiovascular disease (CVD) mortality outcomes among older US adults. Methods: Baseline and follow-up questionnaire data (n = 177,410) were used to calculate weight, physical activity, and diet components of the 2018 WCRF/AICR score (0-7 total points). Adjusted HRs and 95% CIs were estimated, stratified by sex and smoking status. Results: There were 16,055 deaths during a mean of 14.2 person-years. Each 1-point score increase was associated with a 9-26% reduced mortality risk for all outcomes, except for current male smokers' cancer mortality risk. When the score was categorized comparing highest (5-7 points) with lowest (0-2 points) scores, associations with reduced all-cause mortality risk were strongest in former smokers (HRmales: 0.51; 95% CI: 0.43, 0.61; HRfemales: 0.38; 95% CI: 0.31, 0.46), followed by current smokers (HRmales: 0.55; 95% CI: 0.34, 0.89; HRfemales: 0.44; 95% CI: 0.32, 0.59) and never smokers (HRmales: 0.57; 95% CI: 0.47, 0.70; HRfemales: 0.50; 95% CI: 0.41, 0.60). An association with cancer mortality risk was also seen in former smokers (HRmales: 0.59; 95% CI: 0.43, 0.81; HRfemales: 0.52; 95% CI: 0.37, 0.73) and female current (HRfemales: 0.55; 95% CI: 0.32, 0.96) and never (HRfemales: 0.57; 95% CI: 0.40, 0.80) smokers; findings were not statistically significant in other strata. For CVD mortality, highest compared with lowest scores were associated with a 49-73% risk reduction, except in male never and current smokers. In exploratory analysis, physical activity, body weight, alcohol, and plant-based foods were found to be predominant components in the score. Conclusions: Greater 2018 WCRF/AICR scores were associated with lower mortality risk among older adults. Future research can explore how smoking modifies these relations, and further examine different populations and other cancer-relevant outcomes.

Population Attributable Risks of Subtypes of Esophageal and Gastric Cancers in the United States.

INTRODUCTION: To help target preventive strategies, we estimated US population attributable risks (PARs) of demographic and potentially modifiable risk factors for esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric noncardia adenocarcinoma (GNCA). METHODS: We prospectively examined the associations for risk factors and these cancers in 490,605 people in the National Institutes of Health-the American Association of Retired Persons Diet and Health cohort Diet and Health Study cohort from 1995 to 2011. Exposures were obtained from the baseline questionnaire. Diagnoses of gastroesophageal reflux disease were extracted for a subset of eligible National Institutes of Health-the American Association of Retired Persons Diet and Health cohort subjects through linkage to Medicare and then multiply imputed for non-Medicare-eligible subjects. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards regression. Adjusted population attributable risks were calculated for the US population aged 50-71 years by combining the hazard ratios with the estimated joint distribution of risk factor prevalence from the 2015 National Health Interview Survey. RESULTS: Smoking remained the most important risk factor for ESCC and was estimated to cause more than 1/3 of EAC and GCA and 1/10 of GNCA. Obesity and gastroesophageal reflux disease were associated with more than 1/2 of EAC and 1/3 of GCA. Compared with each lowest-risk level category, common risk factors were estimated to be associated with 73.7% of ESCC (95% confidence interval [CI]: 62.1%-85.4%), 70.3% of EAC (95% CI: 64.4%-76.2%), 69.3% of GCA (95% CI: 61.0%-77.7%), and 33.6% of GNCA (95% CI: 21.7%-45.5%). DISCUSSION: These factors accounted for a large proportion of esophageal and gastric cancers in the United States, highlighting opportunities for education and intervention to reduce the burden of these highly fatal cancers.

Gastroesophageal reflux disease: A risk factor for laryngeal squamous cell carcinoma and esophageal squamous cell carcinoma in the NIH-AARP Diet and Health Study cohort.

BACKGROUND: Prior studies have suggested that gastroesophageal reflux disease (GERD) may be associated with risk of squamous cancers of the larynx and esophagus; however, most of these studies have had methodological limitations or insufficient control for potential confounders. METHODS: We prospectively examined the association between GERD and esophageal adenocarcinoma (EADC), esophageal squamous cell carcinoma (ESCC), and laryngeal squamous cell carcinoma (LSCC) in 490,605 participants of the NIH-AARP Diet and Health Study cohort who were 50-71 years of age at baseline. Exposure to risk factors were obtained from the baseline questionnaire. GERD diagnosis was extracted among eligible participants via linkage to Medicare diagnoses codes and then multiply imputed for non-Medicare-eligible participants. Hazard ratios (HRs) and 95% CIs of GERD were computed using Cox regression. RESULTS: From 1995 to 2011, we accrued 931 cases of EADC, 876 cases of LSCC, and 301 cases of ESCC in this cohort and estimated multivariable-adjusted HRs of 2.23 (95% CI, 1.72-2.90), 1.91 (95% CI, 1.24-2.94), and 1.99 (95% CI, 1.39-2.84) for EADC, LSCC, and ESCC, respectively. The associations were independent of sex, smoking status, alcohol intake, and follow-up time periods. We estimated that among the general population in the United States, 22.04% of people aged 50-71 years suffered from GERD. Using risk factor distributions for the United States from national survey data, 16.92% of LSCC cases and 17.32% of ESCC cases among individuals aged 50-71 years were estimated to be associated with GERD. CONCLUSION: GERD is a common gastrointestinal disorder, but future prospective studies are needed to replicate our findings. If replicated, they may inform clinical surveillance of GERD patients and suggest new avenues for prevention of these malignancies.

Alignment of Dietary Patterns With the Dietary Guidelines for Americans 2015-2020 and Risk of All-Cause and Cause-Specific Mortality in the Women's Health Initiative Observational Study.

Poor diet quality is a leading risk factor for death in the United States. We examined the association between Healthy Eating Index-2015 (HEI-2015) scores and death from all causes, cardiovascular disease (CVD), cancer, Alzheimer disease, and dementia not otherwise specified (NOS) among postmenopausal women in the Women's Health Initiative Observational Study (1993-2017). This analysis included 59,388 participants who completed a food frequency questionnaire and were free of cancer, CVD, and diabetes at enrollment. Stratified Cox proportional hazards models were fit using person-years from enrollment as the underlying time metric. We estimated multivariable adjusted hazard ratios and 95% confidence intervals for risk of death associated with HEI-2015 quintiles, with higher scores reflecting more optimal diet quality. Over a median of 18.2 years, 9,679 total deaths 3,303 cancer deaths, 2,362 CVD deaths, and 488 deaths from Alzheimer disease and dementia NOS occurred. Compared with those with lower scores, women with higher HEI-2015 scores had an 18% lower risk of all-cause death and 21% lower risk of cancer death. HEI-2015 scores were not associated with death due to CVD, Alzheimer disease, and dementia NOS. Consuming a diet aligned with 2015-2020 US dietary guidelines may have beneficial impacts for preventing overall causes of death and death from cancer.

Insulin Resistance in Healthy U.S. Adults: Findings from the National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Insulin is fundamental in two conditions that are epidemic in the United States and globally: obesity and type II diabetes. Given insulin's established mechanistic involvement in energy balance and glucose tolerance, we examined its relationship to common health-related endpoints in a large population-based sample. METHODS: The National Health and Nutrition Examination Survey is a cross-sectional study that uses a complex multistage probability design to obtain a representative sample of the United States population. Adult participants were included from 8 successive 2-year data waves (1999-2014), including 9,224 normal individuals, 7,699 prediabetic, and 3,413 diabetic subjects. The homeostatic model for insulin resistance (HOMA-IR) was available for 20,336 participants and its relationship with demographic, anthropometric, and clinical data was analyzed. We examined the relationship of HOMA-IR to 8 groups of outcome variables: general health, anthropometric/metabolic [waist size, body mass index (BMI)], cardiovascular (blood pressure), lipid [triglycerides, high-density lipoprotein (HDL)], hepatic [alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT)], hematologic [white blood cells (WBC), hemoglobin (Hgb), platelets], inflammatory (C-reactive protein), and nutritional (vitamins D and C, serum folate, and pyridoxine) variables. RESULTS: HOMA-IR was generally strongly, monotonically, and highly significantly associated with adjusted outcomes in normal subjects, although clinical laboratory values were generally within normal bounds across insulin quartiles. In the normal subset, the odds ratio and 95% confidence interval for a quartile change in HOMA-IR for obesity (BMI > 30) was 3.62 (3.30-3.97), and for the highest quintile for the triglyceride/HDL the ratio was 2.00 (1.77-2.26), for GGT it was 1.40 (1.24-1.58), and for WBC it was 1.28 (1.16-1.40). The relationship of HOMA-IR to the various outcomes was broadly similar to that observed in prediabetics and diabetics with a few exceptions. CONCLUSIONS: HOMA-IR levels in a large sample of normal individuals are associated with poorer general health and adverse changes across a wide range of markers. A similar pattern of alterations is observed in prediabetic and diabetic samples. IMPACT: Clinically, checking insulin levels may be helpful to identify patients that merit further observation and are candidates for early interventions.

Development and validation of an individualized risk prediction model for oropharynx cancer in the US population.

BACKGROUND: The incidence of oropharynx cancers has increased substantially in the United States. However, risk stratification tools for the identification of high-risk individuals do not exist. In this study, an individualized risk prediction model was developed and validated for oropharynx cancers in the US population. METHODS: A synthetic, US population-based case-control study was conducted. Oropharynx cancer cases diagnosed at Ohio State University (n = 241) were propensity-weighted to represent oropharynx cancers occurring annually in the United States during 2009-2014 (n = 12,656). Controls (n = 9327) included participants in the National Health and Nutrition Examination Survey (2009-2014) and represented the annual US population aged 30 to 69 years (n = 154,532,508). The individualized 1-year absolute risk of oropharynx cancer was estimated with weighted logistic regression. RESULTS: The risk prediction model included age, sex, race, smoking, alcohol use, lifetime sexual partners, and oral oncogenic human papillomavirus (HPV) status. The model had good discrimination and calibration in split-sample validation (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.92-0.97; observed/expected [O/E], 1.01; 95% CI, 0.70-1.32) and external validation (AUC, 0.87; 95% CI, 0.84-0.90; O/E, 1.08; 95% CI, 0.77-1.39). In the US population, 1-year predicted risks of oropharynx cancer were highest for older individuals (21.1/100,000 for 65- to 69-year-olds), men (13.9/100,000), whites (10.4/100,000), smokers (18.0/100,000 for >20 pack-years), heavy alcohol users (18.4/100,000), and those with prevalent oral oncogenic HPV (140.4/100,000). The risk prediction model provided substantial risk stratification, with approximately 77% of all oropharynx cancers and approximately 99% of HPV-positive oropharynx cancers occurring in the 10% of the US population with the highest model-predicted risk. CONCLUSIONS: This risk prediction model will enable the efficient design of studies to address the outstanding questions pertaining to the natural history, screening, and secondary prevention of oropharynx cancers.

Operationalizing the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations: A Standardized Scoring System.

BACKGROUND: Following the publication of the 2018 World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) Third Expert Report, a collaborative group was formed to develop a standardized scoring system and provide guidance for research applications. METHODS: The 2018 WCRF/AICR Cancer Prevention Recommendations, goals, and statements of advice were examined to define components of the new Score. Cut-points for scoring were based on quantitative guidance in the 2018 Recommendations and other guidelines, past research that operationalized 2007 WCRF/AICR Recommendations, and advice from the Continuous Update Project Expert Panel. RESULTS: Eight of the ten 2018 WCRF/AICR Recommendations concerning weight, physical activity, diet, and breastfeeding (optional), were selected for inclusion. Each component is worth one point: 1, 0.5, and 0 points for fully, partially, and not meeting each recommendation, respectively (Score: 0 to 7-8 points). Two recommendations on dietary supplement use and for cancer survivors are not included due to operational redundancy. Additional guidance stresses the importance of accounting for other risk factors (e.g., smoking) in relevant models. CONCLUSIONS: The proposed 2018 WCRF/AICR Score is a practical tool for researchers to examine how adherence to the 2018 WCRF/AICR Recommendations relates to cancer risk and mortality in various adult populations.

Evaluation of the Healthy Eating Index-2015.

BACKGROUND: The Healthy Eating Index (HEI), a diet quality index that measures alignment with the Dietary Guidelines for Americans, was updated with the 2015-2020 Dietary Guidelines for Americans. OBJECTIVE AND DESIGN: To evaluate the psychometric properties of the HEI-2015, eight questions were examined: five relevant to construct validity, two related to reliability, and one to assess criterion validity. DATA SOURCES: Three data sources were used: exemplary menus (n=4), National Health and Nutrition Examination Survey 2011-2012 (N=7,935), and the National Institutes of Health-AARP (formally known as the American Association of Retired Persons) Diet and Health Study (N=422,928). STATISTICAL ANALYSES: Exemplary menus: Scores were calculated using the population ratio method. National Health and Nutrition Examination Survey 2011-2012: Means and standard errors were estimated using the Markov Chain Monte Carlo approach. Analyses were stratified to compare groups (with t tests and analysis of variance). Principal components analysis examined the number of dimensions. Pearson correlations were estimated between components, energy, and Cronbach's coefficient alpha. National Institutes of Health-AARP Diet and Health Study: Adjusted Cox proportional hazards models were used to examine scores and mortality outcomes. RESULTS: For construct validity, the HEI-2015 yielded high scores for exemplary menus as four menus received high scores (87.8 to 100). The mean score for National Health and Nutrition Examination Survey was 56.6, and the first to 99th percentile were 32.6 to 81.2, respectively, supporting sufficient variation. Among smokers, the mean score was significantly lower than among nonsmokers (53.3 and 59.7, respectively) (P<0.01), demonstrating differentiation between groups. The correlation between diet quality and diet quantity was low (all <0.25) supporting these elements being independent. The components demonstrated multidimensionality when examined with a scree plot (at least four dimensions). For reliability, most of the intercorrelations among the components were low to moderate (0.01 to 0.49) with a few exceptions, and the standardized Cronbach's alpha was .67. For criterion validity, the highest vs the lowest quintile of HEI-2015 scores were associated with a 13% to 23% decreased risk of all-cause, cancer, and cardiovascular disease mortality. CONCLUSIONS: The results demonstrated evidence supportive of construct validity, reliability, and criterion validity. The HEI-2015 can be used to examine diet quality relative to the 2015-2020 Dietary Guidelines for Americans.

Comparing Reported Dietary Supplement Intakes between Two 24-Hour Recall Methods: The Automated Self-Administered 24-Hour Dietary Assessment Tool and the Interview-Administered Automated Multiple Pass Method.

BACKGROUND: The Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24) includes a highly standardized multipass web-based recall that, like the Automated Multiple Pass Method (AMPM), captures detailed information about dietary intake using multiple probes and reminders to enhance recall of intakes. The primary distinction between ASA24 and AMPM is that the ASA24 user interface guides participants, thus removing the need for interviewers. OBJECTIVE: The objective of this study was to compare dietary supplement use reported on self-administered (ASA24-2011) vs interviewer-administered (AMPM) 24-hour recalls. DESIGN: The Food Reporting Comparison Study was an evaluation study designed to compare self-reported intakes captured using the self-administered ASA24 vs data collected via interviewer-administered AMPM recalls. Between 2010 and 2011, 1081 women and men were enrolled from three integrated health care systems that belong to the National Cancer Institute-funded Cancer Research Network: Security Health Plan Marshfield Clinic, Wisconsin; Henry Ford Health System, Michigan; and Kaiser Permanente Northern California, California. Quota sampling was used to ensure a balance of age, sex, and race/ethnicity. Participants were randomly assigned to four groups, and each group was asked to complete two dietary recalls: group 1, two ASA24s; group 2, two AMPMs; group 3, ASA24 first and AMPM second; and group 4, AMPM first and ASA24 second. Dietary supplements were coded using the 2007-2008 National Health and Nutrition Examination Survey Dietary Supplement Database. Analyses used the two one-sided tests, known as TOST, to assess equivalence of reported supplement use between methods. RESULTS: Complete 24-hour dietary recalls that included both dietary and supplement intake data were available for 1076 participants (507 men and 569 women). The proportions reporting supplement use via ASA24 and AMPM were 46% and 43%, respectively. These proportions were equivalent, with a small effect size of less than 20%. There were two exceptions in subgroup analyses: reported use among those 40 to 59 years of age and reported use by non-Hispanic black subjects were higher for ASA24 than AMPM. CONCLUSIONS: This study provides evidence that there is little difference in reported supplement use by mode of administration (ie, interview-administered vs self-administered recall).

Effect of Prophylactic Human Papillomavirus (HPV) Vaccination on Oral HPV Infections Among Young Adults in the United States.

Purpose The incidence of human papilloma virus (HPV)-positive oropharyngeal cancers has risen rapidly in recent decades among men in the United States. We investigated the US population-level effect of prophylactic HPV vaccination on the burden of oral HPV infection, the principal cause of HPV-positive oropharyngeal cancers. Methods We conducted a cross-sectional study of men and women 18 to 33 years of age (N = 2,627) within the National Health and Nutrition Examination Survey 2011 to 2014, a representative sample of the US population. Oral HPV infection with vaccine types 16, 18, 6, or 11 was compared by HPV vaccination status, as measured by self-reported receipt of at least one dose of the HPV vaccine. Analyses accounted for the complex sampling design and were adjusted for age, sex, and race. Statistical significance was assessed using a quasi-score test. Results Between 2011 and 2014, 18.3% of the US population 18 to 33 years of age reported receipt of at least one dose of the HPV vaccine before the age of 26 years (29.2% in women and 6.9% in men; P < .001). The prevalence of oral HPV16/18/6/11 infections was significantly reduced in vaccinated versus unvaccinated individuals (0.11% v 1.61%; Padj = .008), corresponding to an estimated 88.2% (95% CI, 5.7% to 98.5%) reduction in prevalence after model adjustment for age, sex, and race. Notably, the prevalence of oral HPV16/18/6/11 infections was significantly reduced in vaccinated versus unvaccinated men (0.0% v 2.13%; Padj = .007). Accounting for vaccine uptake, the population-level effect of HPV vaccination on the burden of oral HPV16/18/6/11 infections was 17.0% overall, 25.0% in women, and 6.9% in men. Conclusion HPV vaccination was associated with reduction in vaccine-type oral HPV prevalence among young US adults. However, because of low vaccine uptake, the population-level effect was modest overall and particularly low in men.

Dietary Flavonoid Intake Reduces the Risk of Head and Neck but Not Esophageal or Gastric Cancer in US Men and Women.

Background: Flavonoids are bioactive polyphenolic compounds found in fruits, vegetables, and beverages of plant origin. Previous studies have shown that flavonoid intake reduces the risk of certain cancers; however, few studies to date have examined associations of flavonoids with upper gastrointestinal cancers or used prospective cohorts.Objective: Our study examined the association between intake of flavonoids (anthocyanidins, flavan-3-ols, flavanones, flavones, flavonols, and isoflavones) and risk of head and neck, esophageal, and gastric cancers.Methods: The NIH-AARP Diet and Health Study is a prospective cohort study that consists of 469,008 participants. Over a mean 12-y follow-up, 2453 head and neck (including 1078 oral cavity, 424 pharyngeal, and 817 laryngeal), 1165 esophageal (890 adenocarcinoma and 275 squamous cell carcinoma), and 1297 gastric (625 cardia and 672 noncardia) cancer cases were identified. We used Cox proportional hazards regression models to estimate HRs and CIs for the associations between flavonoid intake assessed at study baseline and cancer outcomes. For 56 hypotheses examined, P-trend values were adjusted using the Benjamini-Hochberg (BH) procedure for false discovery rate control.Results: The highest quintile of total flavonoid intake was associated with a 24% lower risk of head and neck cancer (HR: 0.76; 95% CI: 0.66, 0.86; BH-adjusted 95% CI: 0.63, 0.91; P-trend = 0.02) compared with the lowest quintile. Notably, anthocyanidins were associated with a 28% lower risk of head and neck cancer (HR: 0.72; 95% CI: 0.62, 0.82; BH-adjusted 95% CI: 0.59, 0.87; P-trend = 0.0005), and flavanones were associated with a 22% lower risk of head and neck cancer (HR: 0.78; 95% CI: 0.68, 0.89; BH-adjusted 95% CI: 0.64, 0.94; P-trend: 0.02). No associations between flavonoid intake and risk of esophageal or gastric cancers were found.Conclusions: Our results indicate that flavonoid intake is associated with lower head and neck cancer risk. These associations suggest a protective effect of dietary flavonoids on head and neck cancer risk, and thus potential as a risk reduction strategy.

Development and Evaluation of the National Cancer Institute's Dietary Screener Questionnaire Scoring Algorithms.

Background: Methods for improving the utility of short dietary assessment instruments are needed.Objective: We sought to describe the development of the NHANES Dietary Screener Questionnaire (DSQ) and its scoring algorithms and performance.Methods: The 19-item DSQ assesses intakes of fruits and vegetables, whole grains, added sugars, dairy, fiber, and calcium. Two nonconsecutive 24-h dietary recalls and the DSQ were administered in NHANES 2009-2010 to respondents aged 2-69 y (n = 7588). The DSQ frequency responses, coupled with sex- and age-specific portion size information, were regressed on intake from 24-h recalls by using the National Cancer Institute usual intake method to obtain scoring algorithms to estimate mean and prevalences of reaching 2 a priori threshold levels. The resulting scoring algorithms were applied to the DSQ and compared with intakes estimated with the 24-h recall data only. The stability of the derived scoring algorithms was evaluated in repeated sampling. Finally, scoring algorithms were applied to screener data, and these estimates were compared with those from multiple 24-h recalls in 3 external studies.Results: The DSQ and its scoring algorithms produced estimates of mean intake and prevalence that agreed closely with those from multiple 24-h recalls. The scoring algorithms were stable in repeated sampling. Differences in the means were <2%; differences in prevalence were <16%. In other studies, agreement between screener and 24-h recall estimates in fruit and vegetable intake varied. For example, among men in 2 studies, estimates from the screener were significantly lower than the 24-h recall estimates (3.2 compared with 3.8 and 3.2 compared with 4.1). In the third study, agreement between the screener and 24-h recall estimates were close among both men (3.2 compared with 3.1) and women (2.6 compared with 2.5).Conclusions: This approach to developing scoring algorithms is an advance in the use of screeners. However, because these algorithms may not be generalizable to all studies, a pilot study in the proposed study population is advisable. Although more precise instruments such as 24-h dietary recalls are recommended in most research, the NHANES DSQ provides a less burdensome alternative when time and resources are constrained and interest is in a limited set of dietary factors.

Accelerometer-measured dose-response for physical activity, sedentary time, and mortality in US adults.

BACKGROUND: Moderate-to-vigorous-intensity physical activity is recommended to maintain and improve health, but the mortality benefits of light activity and risk for sedentary time remain uncertain. OBJECTIVES: Using accelerometer-based measures, we 1) described the mortality dose-response for sedentary time and light- and moderate-to-vigorous-intensity activity using restricted cubic splines, and 2) estimated the mortality benefits associated with replacing sedentary time with physical activity, accounting for total activity. DESIGN: US adults (n = 4840) from NHANES (2003-2006) wore an accelerometer for ≤7 d and were followed prospectively for mortality. Proportional hazards models were used to estimate adjusted HRs and 95% CIs for mortality associations with time spent sedentary and in light- and moderate-to-vigorous-intensity physical activity. Splines were used to graphically present behavior-mortality relation. Isotemporal models estimated replacement associations for sedentary time, and separate models were fit for low- (<5.8 h total activity/d) and high-active participants to account for nonlinear associations. RESULTS: Over a mean of 6.6 y, 700 deaths occurred. Compared with less-sedentary adults (6 sedentary h/d), those who spent 10 sedentary h/d had 29% greater risk (HR: 1.29; 95% CI: 1.1, 1.5). Compared with those who did less light activity (3 h/d), those who did 5 h of light activity/d had 23% lower risk (HR: 0.77; 95% CI: 0.6, 1.0). There was no association with mortality for sedentary time or light or moderate-to-vigorous activity in highly active adults. In less-active adults, replacing 1 h of sedentary time with either light- or moderate-to-vigorous-intensity activity was associated with 18% and 42% lower mortality, respectively. CONCLUSIONS: Health promotion efforts for physical activity have mostly focused on moderate-to-vigorous activity. However, our findings derived from accelerometer-based measurements suggest that increasing light-intensity activity and reducing sedentary time are also important, particularly for inactive adults.

NHANES 2009-2012 Findings: Association of Sexual Behaviors with Higher Prevalence of Oral Oncogenic Human Papillomavirus Infections in U.S. Men.

The incidence of human papillomavirus (HPV)-positive oropharyngeal cancers is higher and increasing more rapidly among men than women in the United States for unknown reasons. We compared the epidemiology of oral oncogenic HPV infection between men and women ages 14 to 69 years (N = 9,480) within the U.S. National Health and Nutritional Examination Surveys (NHANES) 2009-2012. HPV presence was detected in oral DNA by PCR. Analyses were stratified by gender and used NHANES sample weights. Oral oncogenic HPV prevalence was higher among men than women (6.6% vs. 1.5%, P < 0.001), corresponding to 7.07 million men versus 1.54 million women with prevalent infection at any point in time during 2009-2012. Prevalence increased significantly with age, current smoking, and lifetime number of sexual partners for both genders (adjusted Ptrend < 0.02). However, men had more partners than women (mean = 18 vs. 7, P < 0.001). Although oncogenic HPV prevalence was similar for men and women with 0 to 1 lifetime partners, the male-female difference in prevalence significantly increased with number of lifetime partners (adjusted prevalence differences for none, 1, 2-5, 6-10, 11-20, and 20+ partners = 1.0%, 0.5%, 3.0%, 5.7%, 4.6%, and 9.3%, respectively). Importantly, the per-sexual partner increase in prevalence was significantly stronger among men than among women (adjusted synergy index = 3.3; 95% confidence interval, 1.1-9.7), and this increase plateaued at 25 lifetime partners among men versus 10 partners among women. Our data suggest that the higher burden of oral oncogenic HPV infections and HPV-positive oropharyngeal cancers among men than women arises in part from higher number of lifetime sexual partners and stronger associations with sexual behaviors among men.

Dietary consumption of advanced glycation end products and pancreatic cancer in the prospective NIH-AARP Diet and Health Study.

BACKGROUND: Advanced glycation end products (AGEs) are a heterogeneous group of compounds present in uncooked foods as well as in foods cooked at high temperatures. AGEs have been associated with insulin resistance, oxidative stress, and chronic inflammation in patients with diabetes. Dietary AGEs are an important contributor to the AGE pool in the body. N(ϵ)-(carboxymethyl)lysine (CML) AGE is one of the major biologically and chemically well-characterized AGE markers. The consumption of red meat, which is CML-AGE rich, has been positively associated with pancreatic cancer in men. OBJECTIVES: With the use of a published food CML-AGE database, we estimated the consumption of CML AGE in the prospective NIH-AARP Diet and Health Study and evaluated the association between CML-AGE consumption and pancreatic cancer and the mediating effect of CML AGE on the association between red meat consumption and pancreatic cancer. DESIGN: Multivariate Cox proportional hazard regression models were used to estimate HRs and 95% CIs for pancreatic cancer. RESULTS: During an average of 10.5 y of follow-up, we identified 2193 pancreatic cancer cases (1407 men and 786 women) from 528,251 subjects. With the comparison of subjects in the fifth and the first quintiles of CML-AGE consumption, we observed increased pancreatic cancer risk in men (HR: 1.43; 95% CI: 1.06, 1.93, P-trend = 0.003) but not women (HR: 1.14; 95% CI: 0.76, 1.72, P-trend = 0.42). Men in the highest quintile of red meat consumption had higher risk of pancreatic cancer (HR: 1.35; 95% CI: 1.07, 1.70), which attenuated after adjustment for CML-AGE consumption (HR: 1.20; 95% CI: 0.95, 1.53). CONCLUSION: Dietary CML-AGE consumption was associated with modestly increased risk of pancreatic cancer in men and may partially explain the positive association between red meat and pancreatic cancer.