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.

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.

Association of coffee drinking with total and cause-specific mortality.

BACKGROUND: Coffee is one of the most widely consumed beverages, but the association between coffee consumption and the risk of death remains unclear. METHODS: We examined the association of coffee drinking with subsequent total and cause-specific mortality among 229,119 men and 173,141 women in the National Institutes of Health-AARP Diet and Health Study who were 50 to 71 years of age at baseline. Participants with cancer, heart disease, and stroke were excluded. Coffee consumption was assessed once at baseline. RESULTS: During 5,148,760 person-years of follow-up between 1995 and 2008, a total of 33,731 men and 18,784 women died. In age-adjusted models, the risk of death was increased among coffee drinkers. However, coffee drinkers were also more likely to smoke, and, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality. Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to 1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1 cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for 4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day (P<0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI, 0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84 (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (P<0.001 for trend). Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline. CONCLUSIONS: In this large prospective study, coffee consumption was inversely associated with total and cause-specific mortality. Whether this was a causal or associational finding cannot be determined from our data. (Funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.).

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.

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.

Prediagnostic lifestyle factors and survival after colon and rectal cancer diagnosis in the National Institutes of Health (NIH)-AARP Diet and Health Study.

BACKGROUND: Few studies have examined the relationship of lifestyle factors with mortality among patients with colorectal cancer. METHODS: Among NIH-AARP Diet and Health study participants, 4213 colon and 1514 rectal cancer cases were identified through linkage to state cancer registries and determined date and cause of death using the National Death Index. Lifestyle factors were assessed at baseline and included: healthy diet (measured by Healthy Eating Index 2005 [HEI-2005]), body mass index (BMI), physical activity, alcohol consumption and smoking. The association of factors was examined individually and combined into a lifestyle score with 5-year mortality from all-causes, colorectal cancer, and cardiovascular disease (CVD). Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: Among colon cancer survivors, smokers had increased risk of total mortality (RR = 1.74; 95% CI = 1.45-2.08) and colorectal cancer mortality (RR = 1.46; 95% CI = 1.17-1.82), compared to never smokers. Obese (BMI, ≥ 30) individuals had increased risk of all death (RR = 1.19; 95% CI = 1.02-1.39) and CVD death (RR = 1.84; 95% CI = 1.05-3.23), compared to normal weight (BMI, 18.5 to < 25) individuals. Compared to those with the lowest lifestyle score, those with the highest score had a 34% lower risk of all-cause mortality (RR = 0.66; 95% CI = 0.50-0.87). Among rectal cancer survivors, individuals in the highest quintile of HEI-2005 scores had reduced all-cause mortality (RR = 0.60; 95% CI = 0.42-0.86) compared to those in the lowest. Higher combined lifestyle scores were associated with a 46% lower risk of total mortality (0.54; 0.32-0.91). CONCLUSIONS: Healthier lifestyle before cancer diagnosis was associated with improved overall survival after diagnosis with colorectal 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.

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.

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.

Height, weight, and body mass index associations with gastric cancer subsites.

BACKGROUND: Although excess body weight has been associated with cancers of the gastric cardia, relationships with gastric cancer at other anatomic subsites are not well defined. Furthermore, subsite-specific associations with attained height have not been fully assessed. METHODS: In 1995-1996, 483,700 Whites enrolling in the multi-state NIH-AARP Diet and Health Study self-reported height and weight. Gastric cancers occurring through 31 December 2006 were ascertained from regional population-based registries. We used Cox regression models to estimate cancer hazard ratios (HRs) for sex-specific tertiles of height and weight and for body mass index (BMI) categories of the World Health Organization. RESULTS: One thousand incident cancers (48 % localized to the cardia, 4 % fundus, 6 % corpus, 3 % greater curvature, 6 % lesser curvature, 10 % antrum, 2 % pylorus, 5 % overlapping lesion, and 16 % unspecified) occurred an average of 5.4 years after enrollment. After controlling for effects of age, sex, education, and smoking, we found an inverse association between height and total noncardia cancers (i.e., fundus, corpus, greater and lesser curvatures, antrum, and pylorus), with HRs vs. tertile 1 of 0.65 and 0.71 for tertiles 2 and 3, respectively (p trend = 0.016). Trends were consistent for individual noncardia subsites. In contrast, although weight and BMI were each associated with risk of cardia cancer, neither was associated with total noncardia cancer nor individual subsites. CONCLUSION: Noncardia gastric cancer is associated with short stature but not with high body weight or obesity. The excess risk for shorter adults would be consistent with the known association of chronic H. pylori infection with growth retardation during childhood.

Is estrogen plus progestin menopausal hormone therapy safe with respect to endometrial cancer risk?

Given the strong link between use of unopposed estrogens and development of endometrial cancers, estrogens are usually prescribed with a progestin, particularly for women with intact uteri. Some studies suggest that sequential use of progestins may increase risk; however, the moderating effects of usage patterns or patient characteristics, including body mass index (BMI), are unknown. We evaluated menopausal hormone use and incident endometrial cancer (n = 885) in 68,419 postmenopausal women with intact uteri enrolled in the National Institutes of Health-American Association of Retired Persons Diet and Health study. Participants completed a risk factor questionnaire in 1996-1997 and were followed up through 2006. Hazard rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox regression. Among 19,131 women reporting exclusive estrogen plus progestin use, 176 developed endometrial cancer (RR = 0.88; 95% CI = 0.74-1.06). Long-duration (≥ 10 years) sequential (<15 days progestin per month) estrogen plus progestin use was positively associated with risk (RR = 1.88; 95% CI = 1.36-2.60], whereas continuous (>25 days progestin per month) estrogen plus progestin use was associated with a decreased risk (RR = 0.64; 95% CI = 0.49-0.83). Increased risk for sequential estrogen plus progestin was seen only among thin-to-normal weight women (BMI < 25 kg/m(2); RR = 2.53). Our findings support that specific categories of estrogen plus progestin use increases endometrial cancer risk, specifically long durations of sequential progestins, whereas decreased endometrial cancer risk was observed for users of short-duration continuous progestins. Risks were highest among thin-to-normal weight women, presumably reflecting their lower endogenous estrogen levels, suggesting that menopausal hormones and obesity increase endometrial cancer through common etiologic pathways.

A large prospective investigation of sleep duration, weight change, and obesity in the NIH-AARP Diet and Health Study cohort.

The relationship between sleep and obesity or weight gain in adults, particularly older populations, remains unclear. In a cohort of 83,377 US men and women aged 51-72 years, we prospectively investigated the association between self-reported sleep duration and weight change over an average of 7.5 years of follow-up (1995-2004). Participants were free of cancer, heart disease, and stroke at baseline and throughout the follow-up. We observed an inverse association between sleep duration per night and weight gain in both men (P for trend = 0.02) and women (P for trend < 0.001). Compared with 7-8 hours of sleep, shorter sleep (<5 hours or 5-6 hours) was associated with more weight gain (in kilograms; men: for <5 hours, ß = 0.66, 95% confidence interval (CI): 0.19, 1.13, and for 5-6 hours, ß = 0.12, 95% CI: -0.02, 0.26; women: for <5 hours, ß = 0.43, 95% CI: 0.00, 0.86, and for 5-6 hours, ß = 0.23, 95% CI: 0.08, 0.37). Among men and women who were not obese at baseline, participants who reported less than 5 hours of sleep per night had an approximately 40% higher risk of developing obesity than did those who reported 7-8 hours of sleep (for men, odds ratio = 1.45, 95% CI: 1.06, 1.99; for women, odds ratio = 1.37, 95% CI: 1.04, 1.79). The association between short sleep and excess weight gain was generally consistent across different categories of age, educational level, smoking status, baseline body mass index, and physical activity level.

Risk factors for specific histopathological types of postmenopausal breast cancer in the NIH-AARP Diet and Health Study.

Risk factor associations for rare breast cancer variants are often imprecise, obscuring differences between tumor types. To clarify differences, we examined risk factors for 5 histological types of breast cancer in the National Institutes of Health-AARP Diet and Health Study. Risk factor information was self-reported. We followed 192,076 postmenopausal women aged 50-71 years from 1995-1996 through 2006. During that time period, 5,334 ductal, 836 lobular, 639 mixed ductal-lobular, 216 mucinous, and 132 tubular breast cancers were diagnosed. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Heterogeneity was evaluated using case-only logistic regression. The strongest differences were for menopausal hormone therapy (Pheterogeneity < 0.01) and age at first birth (Pheterogeneity < 0.01). Risk of tubular cancer in relation to current menopausal hormone therapy (for current use vs. never use, hazard ratio (HR) = 4.39, 95% confidence interval (CI): 2.77, 6.96) was several times stronger than risk of other histological types (range of HRs, 1.39-1.75). Older age at first birth was unassociated with risk of mucinous (for ≥30 years vs. 20-24 years, HR = 0.62, 95% CI: 0.27, 1.42) or tubular (HR = 1.08, 95% CI: 0.51, 2.29) tumors, in contrast to clear positive associations with lobular (HR = 1.82, 95% CI: 1.39, 2.37) and mixed ductal-lobular (HR = 1.87, 95% CI: 1.39, 2.51) tumors. Differing associations for hormonal factors and mucinous and tubular cancers suggest etiologies distinct from those of common breast cancers.

Index-based dietary patterns and the risk of prostate cancer in the NIH-AARP diet and health study.

Few studies have investigated the relationship between overall diet and the risk of prostate cancer. We examined the association between 3 diet quality indices-the Healthy Eating Index-2005 (HEI-2005), Alternate Healthy Eating Index-2010 (AHEI-2010), and alternate Mediterranean diet score (aMED)-and prostate cancer risk. At baseline, dietary intake was assessed in a cohort of 293,464 US men in the National Institutes of Health (NIH)-AARP Diet and Health Study. Cox proportional hazards regression was used to estimate hazard ratios. Between 1995 and 2006, we ascertained 23,453 incident cases of prostate cancer, including 2,251 advanced cases and 428 fatal cases. Among men who reported a history of prostate-specific antigen testing, high HEI-2005 and AHEI-2010 scores were associated with lower risk of total prostate cancer (for the highest quintile compared with the lowest, hazard ratio (HR) = 0.92, 95% confidence interval (CI): 0.86, 0.98, P for trend = 0.01; and HR = 0.93, 95% CI: 0.88, 0.99, P for trend = 0.05, respectively). No significant association was observed between aMED score and total prostate cancer or between any of the indices and advanced or fatal prostate cancer, regardless of prostate-specific antigen testing status. In individual component analyses, the fish component of aMED and ω-3 fatty acids component of AHEI-2010 were inversely associated with fatal prostate cancer (HR = 0.79, 95% CI: 0.65, 0.96, and HR = 0.94, 95% CI: 0.90, 0.98, respectively).

Prospective study of ultraviolet radiation exposure and mortality risk in the United States.

Geographic variations in mortality rate in the United States could be due to several hypothesized factors, one of which is exposure to solar ultraviolet radiation (UVR). Limited evidence from previous prospective studies has been inconclusive. The association between ambient residential UVR exposure and total and cause-specific mortality risks in a regionally diverse cohort (346,615 white, non-Hispanic subjects, 50-71 years of age, in the National Institutes of Health (NIH)-AARP Diet and Health Study) was assessed, with accounting for individual-level confounders. UVR exposure (averaged for 1978-1993 and 1996-2005) from NASA's Total Ozone Mapping Spectrometer was linked to the US Census Bureau 2000 census tract of participants' baseline residence. Multivariate-adjusted Cox proportional-hazards models were used to estimate hazard ratios and 95% confidence intervals. Over 12 years, UVR exposure was associated with total deaths (n = 41,425; hazard ratio for highest vs. lowest quartiles (HRQ4 vs. Q1) = 1.06, 95% confidence interval (CI): 1.03, 1.09; Ptrend < 0.001) and with deaths (all Ptrend < 0.05) due to cancer (HRQ4 vs. Q1 = 1.06, 95% CI: 1.02, 1.11), cardiovascular disease (HRQ4 vs. Q1 = 1.06, 95% CI: 1.00, 1.12), respiratory disease (HRQ4 vs. Q1 = 1.37, 95% CI: 1.21, 1.55), and stroke (HRQ4 vs. Q1 = 1.16, 95% CI: 1.01, 1.33) but not with deaths due to injury, diabetes, or infectious disease. These results suggest that UVR exposure might not be beneficial for longevity.

Body mass index and physical activity at different ages and risk of multiple myeloma in the NIH-AARP diet and health study.

Several studies have reported an increased risk of multiple myeloma associated with excess body weight. We investigated the risk of multiple myeloma in relation to separate measures of adiposity and energy balance at different ages in the National Institutes of Health-AARP Diet and Health Study, a large prospective cohort study in the United States. Participants completed a baseline questionnaire (1995-1996; n = 485,049), and a subset of participants completed a second questionnaire (1996-1997; n = 305,618) in which we solicited more detailed exposure information. Hazard ratios and 95% confidence intervals were estimated for the risk of multiple myeloma (overall, n = 813; subset, n = 489) in relation to several measures of obesity and leisure time physical activity. Multiple myeloma risk was associated with increasing body mass index (BMI) at cohort entry (per 5-kg/m(2) increase, hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.00, 1.22); similar associations were observed for BMI at age 50 years (HR = 1.14, 95% CI: 1.02, 1.28), age 35 years (HR = 1.20, 95% CI: 1.05, 1.36), and age 18 years (HR = 1.13, 95% CI: 0.98, 1.32) without adjustment for baseline BMI. Risk of multiple myeloma was not associated with physical activity level at any age. These findings support the hypothesis that excess body weight, both in early adulthood and later in life, is a risk factor for multiple myeloma and suggest that maintaining a healthy body weight throughout life may reduce multiple myeloma risk.

Reproductive factors and kidney cancer risk in 2 US cohort studies, 1993-2010.

Clinical and experimental findings suggest that female hormonal and reproductive factors could influence kidney cancer development. To evaluate this association, we conducted analyses in 2 large prospective cohorts (the National Institutes of Health-AARP Diet and Health Study (NIH-AARP), 1995-2006, and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), 1993-2010). Cohort-specific and aggregated hazard ratios and 95% confidence intervals relating reproductive factors and kidney cancer risk were computed by Cox regression. The analysis included 792 incident kidney cancer cases among 283,952 postmenopausal women. Women who had undergone a hysterectomy were at a significantly elevated kidney cancer risk in both NIH-AARP (hazard ratio = 1.28, 95% confidence interval: 1.09, 1.50) and PLCO (hazard ratio = 1.41, 95% confidence interval: 1.06, 1.88). Similar results were observed for both cohorts after analyses were restricted to women who had undergone a hysterectomy with or without an oophorectomy. For the NIH-AARP cohort, an inverse association was observed with increasing age at menarche (P for trend = 0.02) and increasing years of oral contraceptive use (P for trend = 0.02). No clear evidence of an association with parity or other reproductive factors was found. Our results suggest that hysterectomy is associated with increased risk of kidney cancer. The observed associations with age at menarche and oral contraceptive use warrant further investigation.

Index-based dietary patterns and risk of esophageal and gastric cancer in a large cohort study.

BACKGROUND & AIMS: Diet could affect risk for esophageal and gastric cancers, but associations have been inconsistent. The diet is complex, so studies of dietary patterns, rather than studies of individual foods, might be more likely to identify cancer risk factors. There is limited research on index-based dietary patterns and esophageal and gastric cancers. We prospectively evaluated associations between the Healthy Eating Index-2005 (HEI-2005) and alternate Mediterranean Diet (aMED) scores and risk of esophageal and gastric cancers. METHODS: We analyzed data from 494,968 participants in the National Institutes of Health-AARP Diet and Health study, in which AARP members (age, 51-70 y) completed a self-administered baseline food frequency questionnaire between 1995 and 1996. Their answers were used to estimate scores for each index. RESULTS: During the follow-up period (1995-2006), participants developed 215 esophageal squamous cell carcinomas (ESCCs), 633 esophageal adenocarcinomas (EACs), 453 gastric cardia adenocarcinomas, and 501 gastric noncardia adenocarcinomas. Higher scores from the HEI-2005 were associated with a reduced risk of ESCC (comparing the highest quintile with the lowest quintile: hazard ratio, 0.51; 95% confidence interval, 0.31-0.86; Ptrend = .001) and EAC (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; Ptrend = .01). We observed an inverse association between ESCC, but not EAC, and a higher aMED score (meaning a higher-quality diet). HEI-2005 and aMED scores were not associated significantly with gastric cardia or noncardia adenocarcinomas. CONCLUSIONS: By using data collected from 1995 through 2006 from the National Institutes of Health-AARP Diet and Health Study, HEI-2005 and aMED scores were associated inversely with risk for esophageal cancers, particularly ESCC. Adherence to dietary recommendations might help prevent esophageal cancers.

A large prospective study of risk factors for adenocarcinomas and malignant carcinoid tumors of the small intestine.

PURPOSE: Small intestinal cancer is increasing in the U.S.A, yet little is known about its etiology. Our aim was to prospectively evaluate risk factors for this malignancy by the two main histologic subtypes (adenocarcinomas and carcinoids). METHODS: Hazard ratios and 95% confidence intervals (CI) were estimated for all incident small intestinal cancers (n = 237), adenocarcinomas (n = 84), and malignant carcinoids (n = 124), by demographic and lifestyle factors among 498,376 men and women. RESULTS: Age was the only risk factor for adenocarcinomas (HR for ≥ 65 vs. 50-55 years = 3.12, 95% CI 1.33, 7.31). Age (HR for ≥ 65 vs. 50-55 years = 3.31, 95% CI 1.51, 7.28), male sex (HR = 1.44, 95% CI 1.01, 2.05), body mass index (BMI, HR for ≥ 35 vs. 18.5-< 25 kg/m2 = 1.95, 95% CI 1.06, 3.58), and current menopausal hormone therapy use (HR = 1.94, 95% CI 1.07, 3.50) were positively associated with malignant carcinoids. A family history of any cancer or colorectal cancer (HR = 1.42, 95% CI 0.99, 2.03; 1.61, 0.97, 2.65, respectively), or a personal history of colorectal polyps (HR = 1.51, 95% CI 0.92, 2.46) produced elevated, but not statistically significant, risks for malignant carcinoids. Race, education, diabetes, smoking, physical activity, and alcohol intake were not associated with either histologic subtype. CONCLUSIONS: Risk factors differed according to cancer subtype; only age was associated with adenocarcinomas, whereas age, male sex, BMI, and menopausal hormone therapy use were positively associated with malignant carcinoids.

Healthy lifestyle behaviors and decreased risk of mortality in a large prospective study of U.S. women and men.

Adiposity, insufficient physical activity, cigarette smoking, and poor diet have all been related independently to increased chronic disease risk, but their joint impact on overall health remains unclear. In a cohort of 170,672 women and men aged 51-71 years at baseline in 1996/1997 and followed-up through 2009, we investigated the individual and joint impact of four low-risk lifestyle factors: abdominal leanness (waist circumference <88 cm in women and <102 cm in men); recommended physical activity level (30 min or more of moderate exercise at least 5 times per week or 20 min or more of vigorous exercise at least 3 times per week); long-term non-smoking (never-smoker or quit smoking more than 10 years ago); and healthy diet (Mediterranean diet score within the upper two sex-specific quintiles). During 2,126,089 person-years of follow-up, 20,903 participants died. In multivariate Cox models, statistically significant decreased risks of mortality were observed for the low-risk factors abdominal leanness (relative risk (RR) = 0.86; 95 % confidence interval (CI) = 0.83-0.89), physical activity (RR = 0.86; 95 % CI = 0.84-0.89), non-smoking (RR = 0.43; 95 % CI = 0.42-0.45), and healthy diet (RR = 0.86; 95 % CI = 0.83-0.88). The larger the number of low-risk lifestyle factors, the lower was the mortality risk. The RR comparing adherence to all versus none of the factors was 0.27 (95 % CI = 0.25-0.29). We estimate that 33 % (95 % CI = 30-35 %) of deaths in our cohort were premature and could have been avoided if all study participants had adhered to all low-risk factors.