AARP Diet Research Articles

Carcinogenic industrial air pollution and postmenopausal breast cancer risk in the National Institutes of Health AARP Diet and Health Study

BackgroundChemicals emitted from industrial facilities include known or suspected mammary carcinogens and endocrine disruptors, but epidemiologic studies are limited. We evaluated associations between air emissions of multiple carcinogenic chemicals and postmenopausal breast cancer risk in a large prospective U.S. cohort. MethodsWe used the U.S. Environmental Protection Agency’s Toxics Release Inventory to estimate historical airborne emissions (1987–1995) of 19 known and probable carcinogens for participants enrolled (1995–1996) in the NIH-AARP Diet and Health Study. Among 170,402 women, 15,124 breast cancers were diagnosed through 2018. We constructed inverse distance- and wind-weighted average emissions metrics within 1, 2, 5, and 10 km of the enrollment address for each chemical. We estimated multivariable adjusted HRs and 95 % CIs for categories (quartiles, tertiles, medians) of each chemical in association with breast cancer overall and separately by type (invasive, ductal carcinoma in situ) and estrogen receptor (ER) status. ResultsWe observed an association between benzene emissions and breast cancer risk that was strongest at 1 km (HRQ4 vs. non-exposed = 2.06, 95 %CI: 1.34–3.17; p-trend = 0.001). The magnitude of the association weakened with increasing distance (2 km HRQ4 vs. non-exposed = 1.17, 95 %CI=0.92–1.49; p-trend = 0.19; 5 km HRQ4 vs. non-exposed = 1.05, 95 %CI=0.94–1.16; p-trend = 0.37; 10 km HRQ4 vs. non-exposed = 0.95, 95 %CI=0.89–1.02; p-trend = 0.19) and appeared to be most relevant for invasive rather than intraductal disease. Overall risk was also elevated for vinyl chloride at 5 km (HR≥median vs. non-exposed = 1.20, 95 %CI=1.01–1.43; p-trend = 0.04), but not 2 km or 10 km. We observed suggestive associations for asbestos, trichloroethylene, and styrene in different subgroup analyses, but risk patterns were not clear across distances. Associations with other chemicals were generally null, with limited evidence of heterogeneity by disease type or ER status. ConclusionsAn increased risk of breast cancer associated with relatively high levels of industrial benzene emissions warrants additional study, particularly among participants with diverse sociodemographic characteristics that live in areas with higher density of industrial facilities.

Ethylene oxide emissions and incident breast cancer and non-Hodgkin lymphoma in a US cohort.

Ethylene oxide (EtO) is a carcinogenic gas used in chemical production and to sterilize medical equipment that has been linked to risk of breast and lymphohematopoietic cancers in a small number of occupational studies. We investigated the relationship between environmental EtO exposure and risk of these cancers. Using the US Environmental Protection Agency's Toxics Release Inventory, we estimated historical exposures for National Institutes of Health-AARP Diet and Health Study participants enrolled in 1995-1996. We constructed 2 metrics at 3, 5, and 10 km: 1) distance between residences and EtO-emitting facilities, weighted by the proportion of time the home was downwind of each facility, and 2) distance-weighted, wind direction-adjusted average airborne emissions index (AEI=∑[lbs EtO/km2]). We estimated risk (hazard ratio [HR], 95% confidence interval [CI]) of incident breast cancer (in situ and invasive) among postmenopausal women (n = 173 670) overall and by tumor estrogen receptor status and non-Hodgkin lymphoma in the full cohort (n = 451 945). We observed an increased risk of breast cancer associated with EtO-emitting facilities within 10 km (HR[≤10vs>10] = 1.05, 95% CI = 1.00 to 1.10) that appeared stronger for in situ (HR[≤10vs>10] = 1.13, 95% CI = 1.00 to 1.27) than invasive (HR[≤10vs>10] = 1.03, 95% CI = 0.97 to 1.09) disease. Risk of breast cancer in situ was also increased in the top AEI quartiles, and associations weakened with larger distances (HR[Q4vs0] = 1.60, 95% CI = 0.98 to 2.61; HR[Q4vs0] = 1.28, 95% CI = 0.92 to 1.79; HR[Q4vs0] = 1.25, 95% CI = 1.02 to 1.53 at 3, 5, and 10 km, respectively). No differences in breast cancer risk were observed by estrogen receptor status. We found no clear pattern of increased non-Hodgkin lymphoma risk. A novel potential association between EtO emissions and risk of in situ, but not invasive, breast cancer warrants additional evaluation.

Association of Combined Healthy Lifestyles With Cardiovascular Disease and Mortality of Patients With Diabetes: An International Multicohort Study

ObjectiveTo prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes. Patients and MethodsPatients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health–AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non–current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020. ResultsA total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses. ConclusionThe international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes.

Body Mass Index Trajectories Across the Adult Life Course and Pancreatic Cancer Risk.

Body mass index (BMI) during adulthood has been associated with pancreatic ductal adenocarcinoma (PDAC), however, patterns of body size across the adult life course have not been studied extensively. We comprehensively evaluated the association between adiposity across adulthood and PDAC. We conducted a prospective analysis of 269 480 (162 735 males, 106 745 females) National Institutes of Health-AARP Diet and Health Study participants, aged 50-71 years (1995-1996) who self-reported height and weight history. Participants were followed through December 31, 2011. We examined associations between BMI (kg/m2) at ages 18, 35, 50, and 50-71 (baseline) years, their trajectories determined from latent-class trajectory modeling, and incident PDAC. Cox proportional hazard models were used to calculate multivariable adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). During up to 15.2 years of follow-up, 3092 (2020 males, 1072 females) patients with incident PDAC were identified. BMI at all 4 ages were statistically significantly associated with increased PDAC (per 5-unit increase, HR = 1.09-1.13) with higher magnitude associations in males than females at ages 35 years and older (Pinteraction < .05). Four BMI trajectories were created. Compared with normal-weight maintainers, normal-to-overweight, normal-to-obese class I, and overweight-to-obese class III trajectories had hazard ratios of 1.15 (95% CI = 1.06 to 1.25), 1.39 (95% CI = 1.25 to 1.54), and 1.48 (95% CI = 1.18 to 1.87), respectively (Pinteraction by sex = .07). High BMI and BMI trajectories that result in overweight or obesity during adulthood were positively associated with PDAC, with stronger associations among those with early onset adiposity and those with male sex. Avoidance of excess body weight throughout the adult life course may prevent PDAC.

Association of Adherence to Healthy Lifestyle Recommendations With All-Cause and Cause-Specific Mortality Among Former Smokers

The benefits of smoking cessation are well known, but former smokers have a higher health risk than never smokers. The impact of former smokers' engaging in other aspects of a healthy lifestyle is unclear. To assess the association between adherence to evidence-based lifestyle recommendations and mortality among former smokers. This prospective cohort study included 159 937 participants in the National Institutes of Health-AARP Diet and Health Study of older US adults who completed the baseline and risk factor questionnaires and self-identified as former smokers. Baseline questionnaires were mailed from 1995 to 1996. Data analysis was performed from November 2020 to November 2021. Adherence to evidence-based lifestyle recommendations was scored for body weight (scores, 0-2), diet (scores, 0-3), physical activity (scores, 0-2), and alcohol intake (scores, 0-1) recommendations, with higher scores indicating better adherence. Individual lifestyle adherence scores were summed to make a total adherence score (scores, 0-8). The primary outcomes were all-cause and cause-specific mortality through December 31, 2019, with a mean (SD) follow-up of 18.9 (6.3) years. Hazard ratios (HRs) and 95% CIs were computed using a multivariable Cox proportional hazards regression model. Among 159 937 former smokers (mean [SD] age, 62.6 [5.2] years; 106 912 [66.9%] male; 149 742 [93.6%] White), 86 127 deaths occurred. A higher total adherence score was associated with lower all-cause mortality (HR per unit increase, 0.95; 95% CI, 0.94-0.95). Compared with the lowest total adherence score category (scores, 0-2), the HRs for all-cause mortality were 0.88 (95% CI, 0.86-0.90) for scores of 3 to 4, 0.80 (95% CI, 0.79-0.82) for scores of 5 to 6, and 0.73 (95% CI, 0.71-0.75) for scores of 7 to 8. Associations were observed regardless of health status, comorbid conditions, the number of cigarettes participants used to smoke per day, years since cessation, and age at smoking initiation. When examined individually, the HRs for highest vs lowest adherence score were 0.86 (95% CI, 0.84-0.88) for body weight, 0.91 (95% CI, 0.90-0.93) for diet, 0.83 (95% CI, 0.81-0.85) for physical activity, and 0.96 (95% CI, 0.94-0.97) for alcohol intake recommendations. Participants with a higher total adherence score also had a lower risk of mortality from cancer, cardiovascular disease, and respiratory disease. In a large US cohort of former smokers, better adherence to healthy lifestyle recommendations was associated with lower mortality risk. These results provide evidence that former smokers may benefit from adhering to lifestyle recommendations, as do other groups.

Associations of combined healthy lifestyles with cancer morbidity and mortality among individuals with diabetes: results from five cohort studies in the USA, the UK and China.

Cancer has contributed to an increasing proportion of diabetes-related deaths, while lifestyle management is the cornerstone of both diabetes care and cancer prevention. We aimed to evaluate the associations of combined healthy lifestyles with total and site-specific cancer risks among individuals with diabetes. We included 92,239 individuals with diabetes but without cancer at baseline from five population-based cohorts in the USA (National Health and Nutrition Examination Survey and National Institutes of Health [NIH]-AARP Diet and Health Study), the UK (UK Biobank study) and China (Dongfeng-Tongji cohort and Kailuan study). Healthy lifestyle scores (range 0-5) were constructed based on current nonsmoking, low-to-moderate alcohol drinking, adequate physical activity, healthy diet and optimal bodyweight. Cox regressions were used to calculate HRs for cancer morbidity and mortality, adjusting for sociodemographic, medical and diabetes-related factors. During 376,354 person-years of follow-up from UK Biobank and the two Chinese cohorts, 3229 incident cancer cases were documented, and 6682 cancer deaths were documented during 1,089,987 person-years of follow-up in the five cohorts. The pooled multivariable-adjusted HRs (95% CIs) comparing participants with 4-5 vs 0-1 healthy lifestyle factors were 0.73 (0.61, 0.88) for incident cancer and 0.55 (0.46, 0.67) for cancer mortality, and ranged between 0.41 and 0.63 for oesophagus, lung, liver, colorectum, breast and kidney cancers. Findings remained consistent across different cohorts and subgroups. This international cohort study found that adherence to combined healthy lifestyles was associated with lower risks of total cancer morbidity and mortality as well as several subtypes (oesophagus, lung, liver, colorectum, breast and kidney cancers) among individuals with diabetes.

Association of Leisure Time Physical Activity Types and Risks of All-Cause, Cardiovascular, and Cancer Mortality Among Older Adults

Higher amounts of physical activity are associated with increased longevity. However, whether different leisure time physical activity types are differentially associated with mortality risk is not established. To examine whether participation in equivalent amounts of physical activity (7.5 to <15 metabolic equivalent of task [MET] hours per week) through different activity types is associated with mortality risk and to investigate the shape of the dose-response association. Participants in this cohort were respondents from the National Institutes of Health-AARP Diet and Health Study who completed the follow-up questionnaire between 2004 and 2005. This questionnaire collected data on weekly durations of different types of physical activities. Mortality was ascertained through December 31, 2019. MET hours per week spent participating in the following activities: running, cycling, swimming, other aerobic exercise, racquet sports, golf, and walking for exercise. All-cause, cardiovascular, and cancer mortality. Separate multivariable-adjusted Cox proportional hazards regression models were fitted to estimate hazard ratios (HRs) and 95% CIs of mortality for each of the 7 types of leisure time physical activities, as well as the sum of these activities. A total of 272 550 participants (157 415 men [58%]; mean [SD] age at baseline, 70.5 [5.4] years [range, 59-82 years]) provided information on types of leisure time activity, and 118 153 (43%) died during a mean (SD) follow-up of 12.4 (3.9) years. In comparison with those who did not participate in each activity, 7.5 to less than 15 MET hours per week of racquet sports (HR, 0.84; 95% CI, 0.75-0.93) and running (HR, 0.85; 95% CI, 0.78-0.92) were associated with the greatest relative risk reductions for all-cause mortality, followed by walking for exercise (HR, 0.91; 95% CI, 0.89-0.93), other aerobic activity (HR, 0.93; 95% CI, 0.90-0.95), golf (HR, 0.93; 95% CI, 0.90-0.97), swimming (HR, 0.95; 95% CI, 0.92-0.98), and cycling (HR, 0.97; 95% CI, 0.95-0.99). Each activity showed a curvilinear dose-response association with mortality risk; low MET hours per week of physical activity for any given activity type were associated with a large reduction in mortality risk, with diminishing returns for each increment in activity thereafter. Associations were similar for cardiovascular and cancer mortality. This cohort study of older individuals found differences between different types of leisure time activities and mortality risk, but there were significant associations between participating in 7.5 to less than 15 MET hours per week of any activity and mortality risk.

Postdiagnosis Multivitamin and Individual Vitamin Supplement Use and Mortality Among Patients With Colorectal Cancer in the NIH-AARP Diet and Health Study

ObjectivesWe aimed to evaluate the association of postdiagnostic multivitamin and individual vitamin supplement use with total and cancer-specific mortality among colorectal cancer (CRC) survivors.MethodsIn the National Institutes of Health (NIH)–AARP Diet and Health Study, we estimated the associations between vitamin use and total mortality and cancer-specific mortality risk among 2,136 CRC survivors. Use of multivitamin and individual vitamins (vitamin A, vitamin C, vitamin E, beta-carotene, and calcium) were assessed by a food-frequency questionnaire at baseline in 1995–1996 and follow-up questionnaire in 2004–2005. Participants reported frequency of use as never, < 1 time per week, 1–3 times per week, 4–6 times per week, or every day and categories were assigned a corresponding value (never = 0, < 1 time per week = 0.5, 1–3 times per week = 2, 4–6 times per week = 5, and every day = 7). Based on the sum of these values, participants were assigned to one of the following groups: never use (0 times/week), casual use (>0 to 6 times/week), consistent use (7 times/week), or heavy use (>7 times/week). Vital status was ascertained annually by linkage to the Social Security Administration Death Master File and the National Death Index Plus through December 31, 2019. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models with age as the underlying time metric and adjusting for potential confounders.ResultsPostdiagnosis multivitamin use was not associated with all-cause mortality or CRC-specific mortality, but consistent, as compared with never, postdiagnosis vitamin A use was associated with a 12% lower risk of total mortality (HR: 0.88, 95% CI: 0.78–1.00). Consistent, as compared with never, postdiagnosis vitamin C and calcium use were also associated with lower risk of total mortality (HR: 0.86, 95% CI: 0.75–0.99 and HR: 0.84 95% CI: 0.73–0.97, respectively). Use of vitamin E or beta-carotene supplements were not associated with total mortality or CRC-specific mortality.ConclusionsIn the NIH-AARP cohort, consistent use of vitamin A, vitamin C, and calcium but not multivitamins was associated with lower total mortality and CRC-specific mortality among CRC cancer survivors.Funding SourcesThis work was supported by the NCI Intramural Research Program.

Adherence to 5 Diet Quality Indices and Pancreatic Cancer Risk in a Large US Prospective Cohort.

Few prospective studies have examined associations between diet quality and pancreatic ductal adenocarcinoma (PDAC), or comprehensively compared diet quality indices. We conducted a prospective analysis of adherence to the Healthy Eating Index (HEI)-2015, alternative HEI-2010, alternate Mediterranean diet (aMed), and 2 versions of Dietary Approaches to Stop Hypertension (DASH; Fung and Mellen) and PDAC within the National Institutes of Health (NIH)-AARP Diet and Health Study (United States, 1995-2011). The dietary quality indices were calculated using responses from a 124-item food frequency questionnaire completed by 535,824 participants (315,780 men and 220,044 women). We used Cox proportional hazards regression models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each diet quality index and PDAC. During follow-up through 2011 (15.5-year median), 3,137 incident PDAC cases were identified. Compared with those with the lowest adherence quintile, participants with the highest adherence to the HEI-2015 (HR = 0.84, 95% CI: 0.75, 0.94), aMed (HR = 0.82, 95% CI: 0.73, 0.93), DASH-Fung (HR = 0.85, 95% CI: 0.77, 0.95), and DASH-Mellen (HR = 0.86, 95% CI: 0.77, 0.96) had a statistically significant, lower PDAC risk; this was not found for the alternative HEI-2010 (HR = 0.93, 95% CI: 0.83, 1.04). This prospective observational study supports the hypothesis that greater adherence to the HEI-2015, aMed, and DASH dietary recommendations may reduce PDAC.

Lifetime high occupational physical activity and total and cause-specific mortality among 320 000 adults in the NIH-AARP study: a cohort study

ObjectivesWe examined the associations of history and duration in high occupational physical activity (OPA) with long-term total and cause-specific mortality.MethodsThe sample included 322 126 participants (135 254 women) from the...

Abstract 850: Multivitamin use and risk of overall and site-specific cancer in the National Institutes of Health - AARP Diet and Health Study

Abstract Although multivitamins are among the most commonly used supplements in the U.S., their effectiveness in preventing cancer and other chronic diseases is unclear. To help address this uncertainty, we prospectively investigated the association between multivitamin use and risk of overall and site-specific cancer in 489,640 participants enrolled in the National Institutes of Health (NIH) - AARP Diet and Health Study. We defined site-specific cancers using the Surveillance Epidemiology and End Results (SEER) incidence and the International Classification of Diseases for Oncology coding (3rd ed.). Multivitamin use was assessed by questionnaire at baseline and categorized as never, &amp;lt;3 times per week, 3-6 times per week, daily, and &amp;gt;1 per day. Cox proportional hazards regression models of multivitamin use estimated hazard ratios (HRs) and 95% confidence intervals (CIs) that adjusted for multiple potential confounders including gender, age, body mass index, smoking status, and Healthy Eating Index-2015 (HEI-2015) score. We observed no association between increasing multivitamin use and overall cancer risk (HRs 1.0 (reference, never use) 0.94, 0.96, 1.01, 1.00; trend P-value=0.42). Multivitamin use was, however, inversely associated with colon cancer risk: HR=0.79, 95% CI=0.70-0.89 (trend P-value&amp;lt;0.0001) among participants taking &amp;gt;1 multivitamin daily compared with never users, a finding that was identical in men and women (HR=0.79, 95% CI=0.68-0.92 and HR=0.79, 95% CI=0.65-0.95, respectively). Although there were some additional suggestive findings (e.g., for oropharyngeal cancer and leukemia), multivitamin use was not associated with the risk of cancer of the breast, prostate, or lung. In this study that comprehensively evaluated multivitamin use in relation to the risk of overall and site-specific malignancies in both men and women, we found little evidence to support beneficial associations, with the exception of colon cancer risk in both sexes. Citation Format: Jungeun Lim, Stephanie J. Weinstein, Linda M. Liao, Jiaqi Huang, Demetrius Albanes. Multivitamin use and risk of overall and site-specific cancer in the National Institutes of Health - AARP Diet and Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 850.

Abstract 787: Estimating the influence of sex on cancer risk: An analysis in a large US prospective cohort study

Abstract Historically in the United States, cancer incidence has been significantly higher in men than women. This disparity is often attributed to gender-related behavioral risk factors, such as smoking and drinking. The degree to which differences in age-adjusted cancer rates are due to sex (e.g., chromosomes, hormones) is unknown. We estimated the effect of sex on cancer risk by comparing cancer incidence at 21 shared sites between men and women while adjusting for known gender-related risk factors. We analyzed data from 122,826 women and 171,274 men enrolled in the NIH AARP Diet and Health Study (1995-2011), contributing 3.5 million person-years of follow-up. Cox proportional hazards models were used to estimate male-to-female (M:F) adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for each of the cancers, controlling for relevant baseline cancer-specific demographic (age, race, marital status, education), lifestyle (self-reported health status, family history of cancer, diet, body mass index, physical activity), and behavioral factors (tobacco, alcohol use). We used the Peters-Belson method to partition the observed differences between the sexes in cancer incidence into the proportion of the difference explained by the modifiable environmental and behavioral exposures (explained disparity) and the remaining proportion that cannot be explained by these exposures (unexplained disparity). After adjustment for cancer-specific risk factors, risks remained significantly higher in men for nearly all sites. The highest M:F aHR was for esophageal adenocarcinoma (aHR: 10.59, 95% CI: 7.19, 15.61) followed by gastric cardia (aHR: 4.55, 95% CI: 3.28, 6.31) and larynx (aHR: 3.73, 95% CI: 2.84, 4.89) cancers. In contrast, men had a lower adjusted incidence of thyroid (aHR: 0.57, 95% CI: 0.48, 0.68) and gallbladder (aHR: 0.55, 95% CI: 0.37, 0.82) cancers compared with women. Using the Peters-Belson method we found that, if men had the same exposure distribution as the women (under a counterfactual), the male predominance would remain for 12 cancers (bladder, skin, lung, colon, kidney, rectum, esophageal adenocarcinoma, larynx, gastric cardia, esophageal squamous cell carcinoma, pancreas, and oropharynx). For 4 cancers (liver, gastric non-cardia, oral cavity, and anus), if men had the exposure distribution of women, they would have experienced a higher cancer incidence than what was observed. This elevated risk in men compared with women, after adjustment for risk factors, indicates potential innate sex differences across nearly all shared cancer sites. Funding: Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics Citation Format: Sarah S. Jackson, Morgan A. Marks, Hormuzd Katki, Barry I. Graubard, Michael D. Cook, Anil Chaturvedi. Estimating the influence of sex on cancer risk: An analysis in a large US prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 787.

Optimum Amount and Mode of Physical Activity in Association with All-Cause and Cause-Specific Mortality: A Large Prospective Cohort Study

Background: Evidence on amount and mode of physical activity (PA) is optimum for human health is limited. We aimed to determine the optimum amount and mode of PA in association with mortality. Methods: The data of this study was from the US National Institutes of Health–AARP Diet and Health Study from 1995 to 2011. PA was acquired using a self-report questionnaire. We used restricted cubic splines to fit PA time and amount for Cox proportional hazards of mortality. Cox proportional hazards regression was used to generate multivariable-adjusted hazard ratio (HR) and 95%CI of mortality. Results: 266,072 participants were included in this study. During a median follow-up of 7.12 years, there were 36,006 deaths from all cause. Anyway, compared with participants without PA, those with any amount of PA had lower risk of all-cause mortality; furthermore, the risk of all-cause mortality decreased rapidly until around 15.0 hours or 50.0 MET-hours per week of total PA, but the sharply decreasing trend of all-cause mortality risk was changed to slightly decreasing trend while time or amount of all PA increased. Similar trends were also observed in participants with light, moderate and vigorous PA, respectively. Compared participants without PA, those with the combination of 0.1 ~5.0 hours per week light PA, ≥5.0 hours per week moderate PA and ≥1.3 hours per week vigorous PA had relatively lowest risk not only for all-cause mortality, but also for cancer-cause, cardiovascular disease-cause, respiratory disease-cause and diabetes-cause mortality. Conclusions: This study found that any amount and intensity of PA certainly benefited on lowering mortality among all populations with different characteristics, and based on input-output ratio, up to 15.0 hours or 50.0 MET-hours per week of PA is optimal. The mode of combined light, moderate and vigorous PA is recommended. Funding: This study was funded by Chinese National Natural Science Foundation (81973055), Major research and development projects of Zhejiang science and Technology Department (2018C03010) and the Fundamental Research Funds for the Central Universities. Declaration of Interest: There was no conflict of interest. Ethical Approval: The NIH-AARP study was approved by the Special Studies Institutional Review Board of the National Cancer Institute, and all participants gave written informed consent.

Increased frequency of intentional weight loss associated with reduced mortality: a prospective cohort analysis

BackgroundDue to the high prevalence of obesity and the difficulty in maintaining weight loss, repeated bouts of weight loss are a common occurrence. However, there are inconsistencies in epidemiological studies regarding repetitive weight fluctuations being associated with increased risk of mortality. Therefore, the purpose of this prospective cohort analysis was to determine the long-term association of the frequency of weight loss attempts on mortality.MethodsThis prospective cohort study used data collected from adult AARP members living in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, or Pennsylvania) or 2 metropolitan areas (Atlanta, Georgia, or Detroit, Michigan) and participating in the National Institutes of Health–AARP Diet and Health Study between 2004 and 2006. Self-reported data were analyzed for 161,738 middle-aged adults. During an average 7 years of follow-up, 21,194 deaths were recorded. Hazard ratios of all-cause, cardiovascular, and cancer mortality were estimated adjusting for demographic, lifestyle, and behavioral risk factors.ResultsIncreased frequency of weight loss attempts of at least five pounds was associated with lower mortality (ptrend < 0.010). Multivariate hazard ratios (95% confidence intervals) for all-cause death among individuals who successfully attempted weight loss compared with those who did not make any attempts were 0.94 (0.90–0.98) for 1–2 attempts, 0.96 (0.91–1.01) for 3–4 attempts, 0.91 (0.85–0.96) for 5–6 attempts, 0.91 (0.85–0.98) for 7–8 attempts, 0.87 (0.80–0.95) for 9–10 attempts, and 0.88 (0.82–0.94) for 11+ attempts. Similar results were noted for men and women, participants with healthy weight and overweight/obesity, and even among those who gained weight over time. Protective associations were also observed for deaths due to cardiovascular disease and cancer.ConclusionsIncreased frequency of intentionally losing at least five pounds in mid-life was associated with a lower risk of future death. Repeated attempts with moderate amounts of weight loss may provide benefit in terms of longevity.Trial registration numberClinicalTrials.gov number, NCT00340015

Dietary Polyunsaturated Fat Intake in Relation to Head and Neck, Esophageal, and Gastric Cancer Incidence in the National Institutes of Health-AARP Diet and Health Study.

Recent epidemiologic studies have examined the association of fish consumption with upper gastrointestinal cancer risk, but the associations with n-3 and n-6 polyunsaturated fatty acid (PUFA) subtypes remain unclear. Using the National Institutes of Health-AARP Diet and Health Study (United States, 1995-2011), we prospectively investigated the associations of PUFA subtypes, ratios, and fish with the incidence of head and neck cancer (HNC; n=2,453), esophageal adenocarcinoma (EA; n=855), esophageal squamous cell carcinoma (n=267), and gastric cancer (cardia: n=603; noncardia: n=631) among 468,952 participants (median follow-up, 15.5 years). A food frequency questionnaire assessed diet. Multivariable-adjusted hazard ratios were estimated using Cox proportional hazards regression. A Benjamini-Hochberg (BH) procedure was used for false-discovery control. Long-chain n-3 PUFAs were associated with a 20% decreased HNC and EA risk (for HNC, quintile5 vs. 1 hazard ratio=0.81, 95% confidence interval: 0.71, 0.92, and BH-adjusted Ptrend=0.001; and for EA, quintile5 vs. 1 hazard ratio=0.79, 95% confidence interval: 0.64, 0.98, and BH-adjusted Ptrend=0.1). Similar associations were observed for nonfried fish but only for high intake. Further, the ratio of long-chain n-3:n-6 was associated with a decreased HNC and EA risk. No consistent associations were observed for gastric cancer. Our results indicate that dietary long-chain n-3 PUFA and nonfried fish intake are associated with lower HNC and EA risk.

Abstract 619: Dietary advanced glycation end-products and postmenopausal breast cancer risk in the NIH AARP diet and health study

Abstract Purpose: Advanced glycation end-products (AGE) are hypothesized to be involved in carcinogenesis. We analyzed dietary AGE intake in relation to invasive breast cancer (BC) to advance our knowledge of the impact of diet on BC risk. Methods: Dietary AGE intake was estimated from the food-frequency questionnaire in postmenopausal women in the NIH AARP Diet and Health study, prospective cohort (n=183,548). Incident BC cases were identified through linkage with state cancer registries. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for developing BC according to quintiles of AGE levels. Multivariate regression models were adjusted for established BC risk factors. Results: During a mean follow-up of 12.8 years, 9,851 BCs (1,978 advanced stage) were identified. Median daily AGE intake was 5,932 KU/1,000 kcal (10th- 90th percentile, 3,555 - 8,644). Women with higher AGE intake tended to have lower education level, higher BMI, younger age at menarche, menopause, first birth, more children, less physical activity, current smoking and higher total fat and meat intake. AGE intake was associated with increased risk of BC in the multivariate model 1, but the association was attenuated and no longer significant after adjusting for total meat and fat intakes (Table). The association between AGE intake and BC did not differ by BMI, hormone therapy use, or alcohol consumption. AGE intake was not related to BC hormone receptor status, histologic type, or grade. However, AGE intake was associated with increased risks of advanced stage tumors (highest vs. lowest quintile of AGE intake, RR 1.37 95% CI 1.09-1.74) even after controlling for total meat and fat intakes. The risk of advanced stage BC increased by 14% (RR 1.14 95% CI 1.04-1.25 in multivariate model 2) per 2,500 KU/1,000 kcal increase in AGE intake. Conclusions: Dietary AGEs may play a role in the development of postmenopausal BC, particularly in advanced stage BC. Relative Risks (95% CI) of breast cancer for quintiles of AGE intakeQuintiles of AGE intake12345P valueContinuous AGETotal invasive breast cancerNo. of cases1,8992,0231,9321,9952,002Age-adjusted model1 reference1.07 (1.01-1.14)1.03 (0.97-1.10)1.08 (1.01-1.15)1.10 (1.04-1.17).0051.05 (1.02-1.07)Multivariate model 11 reference1.06 (0.99-1.13)1.01 (0.95-1.08)1.05 (0.99-1.12)1.09 (1.02-1.16).031.04 (1.02-1.07)Multivariate model 21 reference1.00 (0.93-1.08)0.94 (0.86-1.02)0.96 (0.88-1.06)1.00 (0.90-1.11).991.03 (0.99-1.08)StageLocalizedNo. of cases1,0211,0169741,001989Age-adjusted model1 reference1.00 (0.92-1.09)0.97 (0.88-1.05)1.00 (0.92-1.09)1.01 (0.92-1.10).891.02 (0.99-1.06)Multivariate model 11 reference0.99 (0.90-1.08)0.95 (0.87-1.04)0.98 (0.90-1.07)1.00 (0.92-1.10).921.02 (0.98-1.06)Multivariate model 21 reference0.90 (0.81-0.99)0.84 (0.75-0.94)0.86 (0.76-0.98)0.90 (0.78-1.04).321.02 (0.96-1.09)Distant/RegionalNo. of cases341414377408438Age-adjusted model1 reference1.22 (1.06-1.41)1.12 (0.97-1.29)1.22 (1.05-1.41)1.33 (1.15-1.53)&amp;lt;.0011.11 (1.05-1.17)Multivariate model 11 reference1.21 (1.04-1.39)1.10 (0.94-1.27)1.18 (1.02-1.37)1.28 (1.11-1.48).0041.09 (1.03-1.16)Multivariate model 21 reference1.25 (1.06-1.47)1.15 (0.95-1.40)1.25 (1.02-1.54)1.37 (1.09-1.74).021.14 (1.04-1.25) Citation Format: Lindsay L. Peterson, Seho Park, Yikyung Park, Narges Anbardar, David Turner. Dietary advanced glycation end-products and postmenopausal breast cancer risk in the NIH AARP diet and health study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 619.

Alcohol consumption and risk of multiple myeloma in the NIH-AARP Diet and Health Study.

The epidemiologic evidence regarding the relationship between alcohol consumption and multiple myeloma (MM) risk remains limited and inconsistent, although recent studies suggest a potential protective effect. We prospectively investigated the risk of MM in relation to alcohol consumption frequency among 499,292 participants enrolled in the National Institutes of Health (NIH)-AARP Diet and Health Study in 1995-1996. A total of 1,312 MM cases were identified during follow-up through December 2011. Hazard ratios (HR) and 95% confidence intervals (CI) for categories of alcohol consumption relative to those defined as light drinkers (<1 drink/week) were estimated using multivariate Cox proportional hazard models. Overall, increasing frequency of alcohol consumption was inversely associated with MM (p-trend = 0.01), with a statistically significant association among those who consumed 2 drinks per day (HR = 0.70, 95% CI: 0.50, 0.98); similar but not statistically significant associations were observed for greater frequency of alcohol consumption. Among women, risk of MM was reduced among those who consumed less than one drink per day (HR = 0.73, 95% CI: 0.56, 0.97) and associations with greater frequency of alcohol consumption were inverse although not statistically significant. The findings of this large prospective investigation suggest that moderate alcohol consumption may be associated with reduced future risk of MM.

Prostate cancer risk factors in black and white men in the NIH-AARP Diet and Health Study.

There are few prospective studies comparing race-specific associations between diet, nutrients, and health-related parameters, and prostate cancer risk. Race-specific prostate cancer risk associations were examined among men in the National Institutes of Health (NIH)-AARP Diet and Health Study. We identified 1417 cases among black men (209 advanced), and 28,845 among white men (3898 advanced). Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). We also evaluated the cumulative change in the HR for black race following adjustment for each factor. Race-specific prostate cancer associations were similar in black and white men across disease subtypes only for history of diabetes (overall : HR = 0.77, 95% CI: 0.65-0.90 and HR = 0.72, 95% CI: 0.69-0.76, respectively; Pinteraction = 0.66). By contrast, there was apositive risk association with height for white men and inverse for black men (Pinteraction: non-advanced = 0.01; advanced = 0.04). This difference remained among men with at least 2 years of follow-up for non-advanced (Pinteraction = 0.01), but not advanced disease (Pinteraction = 0.24); or after adjustment for prostate cancer screening (non-advanced Pinteraction = 0.53, advanced Pinteraction = 0.31). The only other evidence of interaction with race was observed for dietary vitamin D intake and non-advanced disease, but only after adjustment for screening (Pinteraction = 0.02). Cumulative adjustment for each factor increased the HR for black race by 32.9% for overallcancer and 12.4% for advanced disease. Our data suggest few of the dietary, nutrient, and health-related factors associated with prostate cancer risk in predominantly non-Hispanic white men were associated with risk in black men, and adjustment for these factors widen the black-white difference in risk. Larger studies of black men, particularly with prospective data, are needed to help identify risk factors relevant to this population.

Physical activity and sedentary behavior in relation to mortality among renal cell cancer survivors.

BackgroundThe relations of physical activity and sedentary behavior to mortality risk among patients with renal cell cancer have not yet been evaluated.MethodsWe conducted a prospective cohort study among 667 renal cell cancer survivors aged 50–71 years of the National Institutes of Health (NIH)-AARP Diet and Health Study with a median follow-up time of 7.1 years. Post-diagnosis physical activity, TV viewing, and total sitting time were assessed using self-administered questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using Cox proportional hazards models.ResultsIncreasing levels of moderate to vigorous physical activity were related to decreased risk of overall mortality [multivariable-adjusted HRs for <1 hr/wk (reference), 1 to 3 hrs/wk, ≥3 to <7 hrs/wk, and ≥7 hrs/wk = 1.0, 1.16, 0.94, and 0.60 (95% CI = 0.38–0.96; p-trend = 0.03)]. In contrast, television viewing was associated with increased risk of overall mortality in the age- and sex-adjusted model (HR for >4 hrs/d vs. 0 to 2 hrs/d = 1.52, 95% CI = 1.02–2.26; p-trend = 0.04), but the relation was attenuated following further control for other covariates (multivariable-adjusted HR = 1.44, 95% CI = 0.92–2.24; p-trend = 0.11). Total sitting time was unrelated to all-cause mortality.ConclusionAmong renal cancer patients, moderate to vigorous physical activity is associated with decreased risk of overall mortality. Clinicians should consider discussing the potential benefits of physical activity for longevity among survivors of renal cell cancer.

Association of Long-term, Low-Intensity Smoking With All-Cause and Cause-Specific Mortality in the National Institutes of Health–AARP Diet and Health Study

A growing proportion of US smokers now smoke fewer than 10 cigarettes per day (CPD), and that proportion will likely rise in the future. The health effects of smoking only a few CPD over one's lifetime are less understood than are the effects of heavier smoking, although many smokers believe that their level is modest. To evaluate the associations of long-term smoking of fewer than 1 or 1 to 10 CPD (low intensity) with all-cause and cause-specific mortality compared with never smoking cigarettes. Prospective cohort study of 290 215 adults in the National Institutes of Health-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study who were aged 59 to 82 years in calendar years 2004-2005 (baseline). Data were gathered with a questionnaire assessing lifetime cigarette smoking history. Hazard ratios (HRs) and 95% CIs were determined for all-cause mortality and cause-specific mortality through the end of 2011. Hazard ratios and 95% CIs were estimated using Cox proportional hazards regression models using age as the underlying time metric and adjusted for sex, race/ethnicity, educational level, physical activity, and alcohol intake. Data analysis was conducted from December 15, 2015, to September 30, 2016. Current and historical smoking intensity during 9 previous age periods (from <15 years to ≥70 years) over the lifetime assessed on the 2004-2005 questionnaire. All-cause and cause-specific mortality among current, former, and never smokers. Of the 290 215 cohort participants who completed the 2004-2005 questionnaire, 168 140 were men (57.9%); the mean (SD) age was 71 (5.3) years (range, 59-82 years). Most people who smoked fewer than 1 or 1 to 10 CPD at baseline reported smoking substantially higher numbers of CPD earlier in their lives. Nevertheless, 159 (9.1%) and 1493 (22.5%) of these individuals reported consistently smoking fewer than 1 or 1 to 10 CPD in each age period that they smoked, respectively. Relative to never smokers, consistent smokers of fewer than 1 CPD (HR, 1.64; 95% CI, 1.07-2.51) and 1 to 10 CPD (HR, 1.87; 95% CI, 1.64-2.13) had a higher all-cause mortality risk. Associations were similar in women and men for all-cause mortality and were observed across a range of smoking-related causes of death, with an especially strong association with lung cancer (HR, 9.12; 95% CI, 2.92-28.47, and HR, 11.61; 95% CI, 8.25-16.35 for <1 and 1-10 CPD, respectively). Former smokers who had consistently smoked fewer than 1 or 1 to 10 CPD had progressively lower risks with younger age at cessation. For example, the HRs for consistent smokers of fewer than 1 and 1 to 10 CPD who quit at 50 years or older were 1.44 (95% CI, 1.12-1.85) and 1.42 (95% CI, 1.27-1.59), respectively. This study provides evidence that individuals who smoke fewer than 1 or 1 to 10 CPD over their lifetime have higher mortality risks than never smokers and would benefit from cessation. These results provide further evidence that there is no risk-free level of exposure to tobacco smoke.