Aspirin Use and Mortality in Two Contemporary US Cohorts.

BACKGROUND: Daily aspirin use has been recommended for secondary prevention of cardiovascular disease, but its use for primary prevention remains controversial. METHODS: We followed 440,277 men and women from the NIH-AARP Diet and Health Study (ages 50-71) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (ages 55-74) for mortality for 13 years on average. Frequency of aspirin use was ascertained through self-report, and cause of death by death certificates. We calculated multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality using Cox proportional hazards models for each cohort and combined by meta-analysis. RESULTS: We found a consistent U-shaped relationship between aspirin use and mortality in both studies, with differential risk patterns for cardiovascular mortality by disease history. Among individuals with a history of cardiovascular disease, daily aspirin use was associated with reduced cardiovascular mortality [HR = 0.78 (95% CI, 0.74, 0.82)]. However, among those without a previous history, we observed no protection for daily aspirin users [HR = 1.06 (1.02, 1.11)], and elevated risk of cardiovascular mortality for those taking aspirin twice daily or more [HR = 1.29 (1.19, 1.39)]. Elevated risk persisted even among participants who lived beyond 5 years of follow-up and used aspirin without other nonsteroidal antiinflammatory drugs [HR = 1.31 (1.17, 1.47)]. CONCLUSIONS: Results from these 2 large population-based US cohorts confirm the utility of daily aspirin use for secondary prevention of cardiovascular mortality; however, our data suggest that caution should be exercised in more frequent use, particularly among individuals without a history of cardiovascular disease.

Body Mass Index, Waist Circumference, Diabetes, and Risk of Liver Cancer for U.S. Adults.

Incidence rates for liver cancer have increased 3-fold since the mid-1970s in the United States in parallel with increasing trends for obesity and type II diabetes mellitus. We conducted an analysis of baseline body mass index (BMI), waist circumference (WC), and type II diabetes mellitus with risk of liver cancer. The Liver Cancer Pooling Project maintains harmonized data from 1.57 million adults enrolled in 14 U.S.-based prospective studies. Cox regression estimated HRs and 95% confidence intervals (CI) adjusted for age, sex, study center, alcohol, smoking, race, and BMI (for WC and type II diabetes mellitus). Stratified analyses assessed whether the BMI-liver cancer associations differed by hepatitis sera-positivity in nested analyses for a subset of cases (n = 220) and controls (n = 547). After enrollment, 2,162 incident liver cancer diagnoses were identified. BMI, per 5 kg/m2, was associated with higher risks of liver cancer, more so for men (HR = 1.38; 95% CI, 1.30-1.46) than women (HR = 1.25; 95% CI, 1.17-1.35; Pinteraction = 0.02). WC, per 5 cm, was associated with higher risks of liver cancer, approximately equally by sex (overall, HR = 1.08; 95% CI, 1.04-1.13). Type II diabetes mellitus was associated with higher risk of liver cancer (HR = 2.61; 95% CI, 2.34-2.91). In stratified analyses, there was a null association between BMI and liver cancer risk for participants who were sera-positive for hepatitis. This study suggests that high BMI, high WC, and type II diabetes mellitus are associated with higher risks of liver cancer and that the association may differ by status of viral hepatitis infection. Cancer Res; 76(20); 6076-83. ©2016 AACR.

Impact of changing US cigarette smoking patterns on incident cancer: risks of 20 smoking-related cancers among the women and men of the NIH-AARP cohort.

BACKGROUND: Historically, US women started smoking at a later age than men and had lower relative risks for smoking-related cancers. However, more recent birth cohorts of women and men have similar smoking histories and have now reached the high-risk age for cancer. The impact of these changes on cancer incidence has not been systematically examined. METHODS: Relative risks (RR), 95% confidence intervals (CI) and attributable fractions were calculated for cigarette smoking and incidence of 20 smoking-related cancers in 186 057 women and 266 074 men of the National Institutes of Health-AARP cohort, aged 50 to 71 years in 1995 and followed for 11 years. RESULTS: In the cohort, which included participants born between 1924 and 1945, most women and men started smoking as teenagers. RRs for current vs never smoking were similar in women and men for the following cancers: lung squamous-cell (RR women: 121.4, 95% CI: 57.3-257.4; RR men:114.6, 95% CI: 61.2-214.4), lung adenocarcinoma (RR women: 11.7, 95% CI: 9.8-14.0; RR men: 15.6, 95% CI: 12.5-19.6), laryngeal (RR women: 37.0, 95% CI: 14.9-92.3; RR men: 13.8, 95% CI: 9.3-20.2), oral cavity-pharyngeal (RR women:4.4, 95% CI: 3.3-6.0; RR men: 3.8, 95% CI: 3.0-4.7), oesophageal squamous cell (RR women: 7.3, 95% CI: 3.5-15.5; RR men: 6.2, 95% CI: 2.8-13.7), bladder (RR women: 4.7, 95% CI: 3.7-5.8; RR men: 4.0, 95% CI: 3.5-4.5), colon (RR women: 1.3, 95% CI: 1.2-1.5; RR men: 1.3, 95% CI: 1.1-1.4), and at other sites, with similar attributable fractions. CONCLUSIONS: RRs for current smoking and incidence of many smoking-related cancers are now similar in US women and men, likely reflecting converging smoking patterns.

NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project.

Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42-0.98) but not women (HR, 1.34; 95% CI, 0.89-2.01; P(interaction) = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC.

Coffee Consumption and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Sex: The Liver Cancer Pooling Project.

BACKGROUND: Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. METHODS: In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC, n = 860; ICC, n = 260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards regression. RESULTS: Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53-0.99; Ptrend cups/day = <0.0001). More notable reduced risk was seen among women than men (Pinteraction = 0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26-0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63-1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71; 95% CI, 0.50-1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55-1.54). There was no association between coffee consumption and ICC. CONCLUSIONS: These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC. IMPACT: Further research into specific coffee compounds and mechanisms that may account for these associations is needed.

Adolescent and mid-life diet and subsequent risk of thyroid cancer in the NIH-AARP diet and health study.

Although thyroid cancer is suspected to have a nutritional etiology, prospective studies examining the relationship between diet and thyroid cancer are lacking. During 1996-1997, NIH-AARP Diet and Health Study participants, ages 51-72 years, completed a 37-item food frequency questionnaire about diet at ages 12-13 years (adolescence) and 10 years before baseline (mid-life). Over a median 10 years of follow-up, 325 individuals (143 men and 182 women) were diagnosed with thyroid cancer. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for intakes of foods and food groups comparing the highest to the lowest quartiles. Adolescent intakes of chicken/turkey (HR = 1.59, 95% CI: 0.97-2.60; ptrend < 0.01) and sweet baked goods (HR = 1.59, 95% CI: 1.09-2.34; ptrend = 0.04) were positively associated with thyroid cancer risk, while intake of butter/margarine was inversely associated with risk (HR = 0.64, 95% CI: 0.44-0.91; ptrend < 0.02). Similar to adolescent diet, mid-life intake of sweet baked goods was nonsignificantly associated with an increased risk of thyroid cancer (HR = 1.39, 95% CI: 0.96-2.00; ptrend = 0.11), but intake of butter/margarine was inversely associated with risk (HR = 0.66, 95% CI: 0.46-0.95; ptrend = 0.03). Among men, higher adolescent consumption of canned tuna was positively associated with risk of thyroid cancer (HR = 1.69, 95% CI: 1.01-2.83; ptrend = 0.03), and greater mid-life intake of broccoli was associated with a twofold increased risk (HR = 2.13, 95% CI: 1.13-3.99; ptrend < 0.01). This large prospective study suggests that several components of the adolescent and mid-life diet, including iodine-rich foods and goitrogens, may influence thyroid cancer risk.

Adherence to cancer prevention guidelines and cancer incidence, cancer mortality, and total mortality: a prospective cohort study.

BACKGROUND: Several health agencies have issued guidelines promoting behaviors to reduce chronic disease risk; however, little is known about the impact of such guidelines, particularly on cancer incidence. OBJECTIVE: The objective was to determine whether greater adherence to the American Cancer Society (ACS) cancer prevention guidelines is associated with a reduction in cancer incidence, cancer mortality, and total mortality. DESIGN: The NIH-AARP Diet and Health Study, a prospective cohort study of 566,401 adults aged 50-71 y at recruitment in 1995-1996, was followed for a median of 10.5 y for cancer incidence, 12.6 y for cancer mortality, and 13.6 y for total mortality. Participants who reported a history of cancer or who had missing data were excluded, yielding 476,396 subjects for analysis. We constructed a 5-level score measuring adherence to ACS guidelines, which included baseline body mass index, physical activity, alcohol intake, and several aspects of diet. Cox proportional hazards models were used to compute HRs and 95% CIs for the association of the adherence score with cancer incidence, cancer mortality, and total mortality. All analyses included fine adjustment for cigarette smoking. RESULTS: Among 476,396 participants, 73,784 incident first cancers, 16,193 cancer deaths, and 81,433 deaths from all causes were identified in the cohort. Adherence to ACS guidelines was associated with reduced risk of all cancers combined: HRs (95% CIs) for the highest compared with the lowest level of adherence were 0.90 (0.87, 0.93) in men and 0.81 (0.77, 0.84) in women. Fourteen of 25 specific cancer sites showed a reduction in risk associated with increased adherence. Adherence was also associated with reduced cancer mortality [HRs (95% CIs) were 0.75 (0.70, 0.80) in men and 0.76 (0.70, 0.83) in women] and reduced all-cause mortality [HRs (95% CIs) were 0.74 (0.72, 0.76) in men and 0.67 (0.65, 0.70) in women]. CONCLUSIONS: In both men and women, adherence to the ACS guidelines was associated with reductions in all-cancer incidence and the incidence of cancer at specific sites, as well as with reductions in cancer mortality and total mortality. These data suggest that, after accounting for cigarette smoking, adherence to a set of healthy behaviors may have considerable health benefits.

Coffee drinking and cutaneous melanoma risk in the NIH-AARP diet and health study.

BACKGROUND: Cutaneous melanoma is the fifth most common cancer in the United States. Modifiable risk factors, with the exception of exposure to ultraviolet radiation (UVR), are poorly understood. Coffee contains numerous bioactive compounds and may be associated inversely with melanoma. However, previous epidemiological evidence is limited. METHODS: Coffee intake was assessed at baseline with a food frequency questionnaire in the National Institutes of Health-AARP prospective cohort study. Among 447 357 non-Hispanic whites who were cancer-free at baseline, 2904 incident cases of malignant melanoma were identified during 4 329 044 person-years of follow-up, with a median of 10.5 years of follow-up. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coffee intake and subsequent melanoma risk with non-coffee drinkers as the reference group. Statistical tests were two-sided, and P values less than .05 were interpreted as statistically significant. RESULTS: The highest category of coffee intake was inversely associated with malignant melanoma (≥4 cups/day: HR = 0.80, 95% CI = 0.68 to 0.93, P trend = .01). This association was statistically significant for caffeinated (≥4 cups/day: HR = 0.75, 95% CI = 0.64 to 0.89, P trend = .01) but not for decaffeinated coffee (P trend = .55). CONCLUSIONS: Higher coffee intake was associated with a modest decrease in risk of melanoma in this large US cohort study. Additional investigations of coffee intake and its constituents, particularly caffeine, with melanoma are warranted.

Mortality Benefits for Replacing Sitting Time with Different Physical Activities.

PURPOSE: Prolonged sitting has emerged as a risk factor for early mortality, but the extent of benefit realized by replacing sitting time with exercise or activities of everyday living (i.e., nonexercise activities) is not known. METHODS: We prospectively followed 154,614 older adults (59-82 yr) in the National Institutes of Health-AARP Diet and Health Study who reported no major chronic diseases at baseline and reported detailed information about sitting time, exercise, and nonexercise activities. Proportional hazard models were used to estimate adjusted hazard ratios and 95% confidence intervals (HR (95% confidence interval)) for mortality. An isotemporal modeling approach was used to estimate associations for replacing sitting time with specific types of physical activity, with separate models fit for less active and more active participants to account for nonlinear associations. RESULTS: During 6.8 yr (SD, 1.0) of follow-up, 12,201 deaths occurred. Greater sitting time (≥12 vs < 5 h·d(-1)) was associated with increased risk for all-cause and cardiovascular mortality. In less active adults (<2 h·d(-1) total activity), replacing 1 h·d(-1) of sitting with an equal amount of activity was associated with lower all-cause mortality for both exercise (HR, 0.58 (0.54-0.63)) and nonexercise activities (HR, 0.70 (0.66-0.74)), including household chores, lawn and garden work, and daily walking. Among more active participants (2+ h·d(-1) total activity), replacement of sitting time with purposeful exercise was associated with lower mortality (HR, 0.91 (0.88-0.94)) but not with nonexercise activity (HR, 1.00 (0.98-1.02)). Similar results were noted for cardiovascular mortality. CONCLUSIONS: Physical activity intervention strategies for older adults often focus on aerobic exercise, but our findings suggest that reducing sitting time and engaging in a variety of activities is also important, particularly for inactive adults.

Pre- and postdiagnosis physical activity, television viewing, and mortality among patients with colorectal cancer in the National Institutes of Health-AARP Diet and Health Study.

PURPOSE: Physical inactivity has been associated with higher mortality risk among survivors of colorectal cancer (CRC), but the independent effects of pre- versus postdiagnosis activity are unclear, and the association between watching television (TV) and mortality in survivors of CRC is previously undefined. METHODS: We analyzed the associations between prediagnosis (n = 3,797) and postdiagnosis (n = 1,759) leisure time physical activity (LTPA) and TV watching and overall and disease-specific mortality among patients with CRC. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs, adjusting for known mortality risk factors. RESULTS: Comparing survivors of CRC reporting more than 7 hours per week (h/wk) of prediagnosis LTPA with those reporting no LTPA, we found a 20% lower risk of all-cause mortality (HR, 0.80; 95% CI, 0.68 to 0.95; P for trend = .021). Postdiagnosis LTPA of ≥ 7 h/wk, compared with none, was associated with a 31% lower all-cause mortality risk (HR, 0.69; 95% CI, 0.49 to 0.98; P for trend = .006), independent of prediagnosis activity. Compared with 0 to 2 TV hours per day (h/d) before diagnosis, those reporting ≥ 5 h/d of TV before diagnosis had a 22% increased all-cause mortality risk (HR, 1.22; 95% CI, 1.06 to 1.41; P trend = .002), and more postdiagnosis TV watching was associated with a nonsignificant 25% increase in all-cause mortality risk (HR, 1.25; 95% CI, 0.93 to 1.67; P for trend = .126). CONCLUSION: LTPA was inversely associated with all-cause mortality, whereas more TV watching was associated with increased mortality risk. For both LTPA and TV watching, postdiagnosis measures independently explained the association with mortality. Clinicians should promote both minimizing TV time and increasing physical activity for longevity among survivors of CRC, regardless of previous behaviors.

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.

Attained height, sex, and risk of cancer at different anatomic sites in the NIH-AARP diet and health study.

PURPOSE: To examine the association of adult height with risk of cancer at different anatomic sites in a cohort of men and women. METHODS: The association of self-reported height with subsequent cancer risk was assessed in 288,683 men and 192,514 women enrolled in the National Institutes of Health-AARP Diet and Health Study. After a median follow-up of 10.5 years, incident cancer was diagnosed in 51,139 men and 23,407 women. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) for the association of height with cancer risk. RESULTS: After adjustment for covariates, height was positively associated with increased risk of all cancers combined in both men [HR10 cm increase = 1.05 (95 % CI 1.04-1.06)] and women [HR10 cm increase = 1.08 (95 % CI 1.06-1.10)]. Several sites common to men and women showed significant positive associations with height: colon, rectum, kidney, melanoma, and non-Hodgkin's lymphoma. For other shared sites, the association differed by sex. For still other sites, there was no clear association with height. Positive associations were also observed with cancers of the breast, endometrium, and prostate. CONCLUSIONS: Different patterns were observed in the height-cancer association by sex. Studies investigating the biological mechanisms underlying the association of height with cancer risk should focus on those sites that show a reproducible association with attained height.

Sleep duration and total and cause-specific mortality in a large US cohort: interrelationships with physical activity, sedentary behavior, and body mass index.

Both short and long durations of sleep are associated with higher mortality, but little is known about the interrelationship between sleep and other modifiable factors in relation to mortality. In the National Institutes of Health-AARP Diet and Health Study (1995-1996), we examined associations between sleep duration and total, cardiovascular disease (CVD), and cancer mortality among 239,896 US men and women aged 51-72 years who were free of cancer, CVD, and respiratory disease. We evaluated the influence of moderate-to-vigorous physical activity, television viewing, and body mass index (BMI; weight (kg)/height (m)(2)) on the sleep-mortality association and assessed their combined association with mortality. During an average of 14 years of follow-up, we identified 44,100 deaths. Compared with 7-8 hours of sleep per day, both shorter and longer sleep durations were associated with higher total and CVD mortality. We found a greater elevation in CVD mortality associated with shorter sleep among overweight and obese people, suggesting a synergistic interaction between sleep and BMI. People in the unhealthy categories of all 4 risk factors (sleep <7 hours/day, moderate-to-vigorous physical activity ≤1 hour/week, television viewing ≥3 hours/day, and BMI ≥25) had significantly higher all-cause (relative risk (RR) = 1.42, 95% confidence interval (CI): 1.34, 1.52), CVD (RR = 1.90, 95% CI: 1.67, 2.17), and cancer (RR = 1.21, 95% CI: 1.09, 1.34) mortality. Short sleep duration may predict higher mortality, particularly CVD mortality, among overweight and obese people.

A prospective cohort study of body size and risk of head and neck cancers in the NIH-AARP diet and health study.

BACKGROUND: The association between body size and head and neck cancers (HNCA) is unclear, partly because of the biases in case-control studies. METHODS: In the prospective NIH-AARP cohort study, 218,854 participants (132,288 men and 86,566 women), aged 50 to 71 years, were cancer free at baseline (1995 and 1996), and had valid anthropometric data. Cox proportional hazards regression was used to examine the associations between body size and HNCA, adjusted for current and past smoking habits, alcohol intake, education, race, and fruit and vegetable consumption, and reported as HR and 95% confidence intervals (CI). RESULTS: Until December 31, 2006, 779 incident HNCAs occurred: 342 in the oral cavity, 120 in the oro- and hypopharynx, 265 in the larynx, 12 in the nasopharynx, and 40 at overlapping sites. There was an inverse association between HNCA and body mass index, which was almost exclusively among current smokers (HR = 0.76 per each 5 U increase; 95% CI, 0.63-0.93), and diminished as initial years of follow-up were excluded. We observed a direct association with waist-to-hip ratio (HR = 1.16 per 0.1 U increase; 95% CI, 1.03-1.31), particularly for cancers of the oral cavity (HR, 1.40; 95% CI, 1.17-1.67). Height was also directly associated with total HNCAs (P = 0.02), and oro- and hypopharyngeal cancers (P < 0.01). CONCLUSIONS: The risk of HNCAs was associated inversely with leanness among current smokers, and directly with abdominal obesity and height. IMPACT: Our study provides evidence that the association between leanness and risk of HNCAs may be due to effect modification by smoking.

Body size and physical activity in relation to incidence of chronic obstructive pulmonary disease.

BACKGROUND: Limited evidence suggests that adiposity and lack of physical activity may increase the risk of chronic obstructive pulmonary disease (COPD). We investigated the relation of body size and physical activity with incidence of COPD. METHODS: We obtained data on anthropometric measurements and physical activity from 113,279 participants in the National Institutes of Health-AARP Diet and Health Study who reported no diagnosis of COPD at baseline (1995-1996). We estimated associations between these measurements and subsequent diagnosis of COPD between 1996 and 2006, with extensive adjustment for smoking and other potentially confounding variables. RESULTS: Participants reported 3648 new COPD diagnoses during follow-up. The incidence of COPD was higher in both severely obese (body mass index [BMI] ≥ 35) and underweight (BMI < 18.5) participants, but after adjustment for waist circumference, only underweight remained positively associated with COPD (relative risk [RR] 1.56, 95% confidence interval [CI] 1.15-2.11). Larger waist circumference (highest v. normal categories, adjusted RR 1.72, 95% CI 1.37-2.16) and higher waist-hip ratio (highest v. normal categories, adjusted RR 1.46, 95% CI 1.23-1.73) were also positively associated with COPD. In contrast, hip circumference (highest v. normal categories, adjusted RR 0.78, 95% CI 0.62-0.98) and physical activity (≥ 5 v. 0 times/wk, adjusted RR 0.71, 95% CI 0.63-0.79) were inversely associated with COPD. INTERPRETATION: Obesity, in particular abdominal adiposity, was associated with an increased risk of COPD, and increased hip circumference and physical activity were associated with a decreased risk of COPD. These findings suggest that following guidelines for a healthy body weight, body shape and physical activity decrease the risk of COPD.

Breast cancer risk in older women: results from the NIH-AARP Diet and Health Study.

BACKGROUND: Divergent risk factors exist for premenopausal and postmenopausal breast cancers, but it is unclear whether differences by age exist among postmenopausal women. METHODS: We examined relationships among 190,872 postmenopausal women, ages 50-71 years recruited during 1995-1996 for the NIH-AARP Diet and Health Study, in whom 7,384 incident invasive breast carcinomas were identified through 2006. Multivariable Cox regression hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for breast cancer risk factors by age (50-59, 60-69, ≥70 years). RESULTS: The only factor showing significant statistical heterogeneity by age (p(het) = 0.001) was menopausal hormone therapy duration, but trends were apparent across all ages and the strongest association prevailed among women 60-69 years. Although other risk factors did not show statistically significant heterogeneity by age, we did observe attenuated relations for parity and late age at first birth among older women [e.g., HR for age at first birth ≥30 vs. 20-24 = 1.62 (95% CI 1.23-2.14) for women 50-59 years vs. 1.12 (0.96-1.31) for ≥70 years]. In contrast, risk estimates associated with alcohol consumption and BMI tended to be slightly stronger among the oldest subjects [e.g., HR for BMI ≥35 vs. 18.5-24.9 = 1.24 (95% CI 0.97-1.58) for 50-59 years vs. 1.46 (1.26-1.70) for ≥70 years]. These differences were somewhat more pronounced for estrogen receptor positive and ductal cancers, tumors predominating among older women. Breast cancer family history, physical activity, and previous breast biopsies did not show divergent associations by age. CONCLUSION: Although breast cancer risk factor differences among older women were not large, they may merit further consideration with respect to individualized risk prediction.

Sweetened beverages, coffee, and tea and depression risk among older US adults.

Sweetened beverages, coffee, and tea are the most consumed non-alcoholic beverages and may have important health consequences. We prospectively evaluated the consumption of various types of beverages assessed in 1995-1996 in relation to self-reported depression diagnosis after 2000 among 263,923 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regressions. The OR (95% CI) comparing ≥4 cans/cups per day with none were 1.30 (95%CI: 1.17-1.44) for soft drinks, 1.38 (1.15-1.65) for fruit drinks, and 0.91 (0.84-0.98) for coffee (all P for trend<0.0001). Null associations were observed for iced-tea and hot tea. In stratified analyses by drinkers of primarily diet versus regular beverages, the ORs were 1.31 (1.16-1.47) for diet versus 1.22 (1.03-1.45) for regular soft drinks, 1.51 (1.18-1.92) for diet versus 1.08 (0.79-1.46) for regular fruit drinks, and 1.25 (1.10-1.41) for diet versus 0.94 (0.83-1.08) for regular sweetened iced-tea. Finally, compared to nondrinkers, drinking coffee or tea without any sweetener was associated with a lower risk for depression, adding artificial sweeteners, but not sugar or honey, was associated with higher risks. Frequent consumption of sweetened beverages, especially diet drinks, may increase depression risk among older adults, whereas coffee consumption may lower the risk.

Index-based dietary patterns and risk of incident hepatocellular carcinoma and mortality from chronic liver disease in a prospective study.

UNLABELLED: The role of diet in hepatocellular carcinoma (HCC) and its typical precursor, chronic liver disease (CLD), is poorly understood. Following dietary recommendations has been shown to reduce risk of many cancers, but whether such diets are associated with HCC and CLD is unknown. We prospectively evaluated the association of two dietary indices, the Healthy Eating Index-2010 (HEI-2010) and the alternate Mediterranean Diet Score (aMED), with HCC incidence and CLD mortality in a large U.S. prospective cohort. We calculated the HEI-2010 and aMED scores for 494,942 participants in the National Institutes of Health-AARP Diet and Health study, based on typical diet assessed using a food frequency questionnaire FFQ between 1995 and 1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) for quintiles of each index were estimated using Cox's proportional hazards regression, after adjusting for alcohol intake, smoking, body mass index, diabetes, and other covariates. A total of 509 HCC cases (1995-2006) and 1,053 CLD deaths (1995-2011) were documented during follow-up. Higher HEI-2010 scores, reflecting favorable adherence to dietary guidelines, were associated with lower risk of HCC (HR, 0.72, 95% CI: 0.53-0.97 for the highest quintile, compared to lowest; P trend = 0.03) and lower mortality resulting from CLD (HR, 0.57; 95% CI: 0.46-0.71; P trend < 0.0001). High aMED scores were also associated with lower risk of HCC (HR, 0.62; 95% CI: 0.47-0.84; P trend = 0.0002) and lower risk of CLD mortality (HR, 0.52; 95% CI: 0.42-0.65; P trend < 0.0001). CONCLUSIONS: Adhering to dietary recommendations may reduce the risk of developing HCC and dying of CLD.

Dietary flavonoid intake and thyroid cancer risk in the NIH-AARP diet and health study.

Experimental studies suggested that flavonoids may influence thyroid carcinogenesis, but epidemiologic evidence is sparse. No study has examined different classes of flavonoids in relation to thyroid cancer risk. Using data from the NIH-AARP Diet and Health Study, which enrolled 491,840 U.S. men and women, ages 50 to 71 years at baseline, we prospectively examined the risk of thyroid cancer in relation to dietary intakes of catechins, flavanones, flavonols, anthocyanidins, flavones, isoflavones, and total flavonoids. Dietary intakes were assessed using a food frequency questionnaire. Cancer cases were ascertained by linkage to state cancer registries. Multivariable-adjusted Cox proportional hazard models were used to estimate HRs and 95% confidence intervals (CI). During follow up (mean = 9 years), we identified 586 thyroid cancer cases. Thyroid cancer risk was inversely associated with dietary flavan-3-ols [HRQ5 vs. Q1 (95% CI): 0.70 (0.55, 0.91), PTrend = 0.03], but positively associated with flavanones [HRQ5 vs. Q1 (95% CI): 1.50 (1.14, 1.96), PTrend = 0.004]. Other classes of flavonoids and total flavonoids were not associated with thyroid cancer risk. Similar associations were found for papillary thyroid cancer. Our findings suggest that dietary intake of different classes of dietary flavonoids may have divergent effects on thyroid cancer risk. More studies are needed to clarify a role of flavonoids in thyroid cancer development. Results from our study suggest a potential nutritional etiology of thyroid cancer. Cancer Epidemiol Biomarkers Prev; 23(6); 1102-8. ©2014 AACR.