Showing papers by "Arthur Schatzkin published in 2010"

Body-Mass Index and Mortality among 1.46 Million White Adults

Abstract: BACKGROUND A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. METHODS We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). RESULTS The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. CONCLUSIONS In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.

Smoking duration, intensity, and risk of Parkinson disease

Abstract: Objective: To evaluate the relative importance of smoking duration vs intensity in reducing the risk of Parkinson disease (PD). Methods: The study included 305,468 participants of the NIH-AARP Diet and Health cohort, of whom 1,662 had a PD diagnosis after 1995. We estimated odds ratios (OR) and 95% confidence intervals from multivariate logistic regression models. Results: Compared with never smokers, the multivariate ORs were 0.78 for past smokers and 0.56 for current smokers. Among past smokers, a monotonic trend toward lower PD risk was observed for all indicators of more smoking. Stratified analyses indicated that smoking duration was associated with lower PD risk within fixed intensities of smoking. For example, compared with never smokers, the ORs among past smokers who smoked >20 cigarettes/day were 0.96 for 1–9 years of smoking, 0.78 for 10–19 years, 0.64 for 20–29 years, and 0.59 for 30 years or more ( p for trend = 0.001). In contrast, at fixed duration, the typical number of cigarettes smoked per day in general was not related to PD risk. Close examination of smoking behaviors in early life showed that patients with PD were less likely to be smokers at each age period, but if they smoked, they smoked similar numbers of cigarettes per day as individuals without PD. Conclusions: This large study suggests that long-term smoking is more important than smoking intensity in the smoking–Parkinson disease relationship.

Models of carcinogenesis: an overview

Abstract: At least five coherent models of carcinogenesis have been proposed in the history of cancer research in the last century. Model 1 is mainly centered around mutations, and its main focus is on the chemical environment, radiation and viruses. Model 2 has to do mainly with genome instability and it focuses on familiality. Model 3 is based on non-genotoxic mechanisms, and clonal expansion and epigenetics are its main features. We propose a fourth model, which can encompass the previous three, based on the concept of a ‘Darwinian’ cell selection (we clarify that the term Darwinian needs to be used cautiously, being a short cut for ‘somatic cellular selection’). Finally, a fifth model has recently become popular, based on the concept of ‘tissue organization’. We describe examples of the five models and how they have been formalized mathematically. The five models largely overlap, both scientifically and historically, but for the sake of clarity, it is useful to treat them separately. We also argue that the five models can be included into a simpler scheme, i.e. two types of models: (i) biological changes in the epithelium alone lead to malignancy and (ii) changes in stroma/extracellular matrix are necessary (along with changes in epithelium) for malignancy. Our description, though simplified, looks realistic, it is able to capture the historical sequence of carcinogenesis theories in the last century and can serve as a frame to make research hypotheses more explicit.

Day Napping and Short Night Sleeping Are Associated With Higher Risk of Diabetes in Older Adults

Abstract: Objective- To examine whether day napping or short night sleeping is associated with higher risk of diabetes. Research design and methods- A prospective study of hours of daytime napping and night sleeping assessed in 1996-1997 in relation to diabetes diagnosed between 2000 and 2006 (n = 10,143) among 174,542 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regression models. Results- Longer day napping was associated with higher risk of diabetes. After adjusting for potential confounders, compared with individuals who did not nap, the OR was 1.23 (95%CI: 1.18-1.29) for those reporting P for trend P for interaction Conclusions- Day napping and short night sleeping are associated with higher risk of diabetes. The association between sleep duration and diabetes may be modified by napping habit.

Body mass index, effect modifiers, and risk of pancreatic cancer: a pooled study of seven prospective cohorts

Abstract: Objective To investigate whether the positive association of body mass index (BMI, kg/m2) with risk of pancreatic cancer is modified by age, sex, smoking status, physical activity, and history of diabetes.

Risk of Colon Cancer and Coffee, Tea, and Sugar-Sweetened Soft Drink Intake: Pooled Analysis of Prospective Cohort Studies

Abstract: BackgroundThe relationships between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk remain unresolved. MethodsWe investigated prospectively the association between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk in a pooled analysis of primary data from 13 cohort studies. Among 731441 participants followed for up to 6-20 years, 5604 incident colon cancer case patients were identified. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random-effects model. All statistical tests were two-sided. ResultsCompared with nonconsumers, the pooled multivariable relative risks were 1.07 (95% CI = 0.89 to 1.30, Ptrend =. 68) for coffee consumption greater than 1400 g/d (about six 8-oz cups) and 1.28 (95% CI = 1.02 to 1.61, Ptrend =. 01) for tea consumption greater than 900 g/d (about four 8-oz cups). For sugar-sweetened carbonated soft drink consumption, the pooled multivariable relative risk comparing consumption greater than 550 g/d (about 18 oz) to nonconsumers was 0.94 (95% CI = 0.66 to 1.32, Ptrend =. 91). No statistically significant between-studies heterogeneity was observed for the highest category of each beverage consumed (P >. 20). The observed associations did not differ by sex, smoking status, alcohol consumption, body mass index, physical activity, or tumor site (P >. 05). ConclusionsDrinking coffee or sugar-sweetened carbonated soft drinks was not associated with colon cancer risk. However, a modest positive association with higher tea consumption is possible and requires further study. The Author 2010. Published by Oxford University Press. © The Author 2010.

Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer

Abstract: Objective Studies of folate intake and colorectal cancer risk have been inconsistent. We examined the relation with colon cancer risk in a series of 13 prospective studies.

Neighborhood socioeconomic deprivation and mortality: NIH-AARP diet and health study.

Abstract: Purpose Residing in deprived areas may increase risk of mortality beyond that explained by a person's own SES-related factors and lifestyle. The aim of this study was to examine the relation between neighborhood socioeconomic deprivation and all-cause, cancer- and cardiovascular disease (CVD)-specific mortality for men and women after accounting for education and other important person-level risk factors. Methods In the longitudinal NIH-AARP Study, we analyzed data from healthy participants, ages 50–71 years at study baseline (1995–1996). Deaths (n = 33831) were identified through December 2005. Information on census tracts was obtained from the 2000 US Census. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for quintiles of neighborhood deprivation. Results Participants in the highest quintile of deprivation had elevated risks for overall mortality (HRmen = 1.17, 95% CI: 1.10, 1.24; HRwomen = 1.13, 95% CI: 1.05, 1.22) and marginally increased risk for cancer deaths (HRmen = 1.09, 95% CI: 1.00, 1.20; HRwomen = 1.09, 95% CI: 0.99, 1.22). CVD mortality associations appeared stronger in men (HR = 1.33, 95% CI: 1.19, 1.49) than women (HR = 1.18, 95% CI: 1.01, 1.38). There was no evidence of an effect modification by education. Conclusion Higher neighborhood deprivation was associated with modest increases in all-cause, cancer- and CVD-mortality after accounting for many established risk factors.

Prospective study of body mass index, physical activity and thyroid cancer.

Abstract: Increased body size and physical inactivity are positively related to risk of several cancers, but only few epidemiologic studies have investigated body-mass index (BMI) and physical activity in relation to thyroid cancer. We examined the relations of BMI and physical activity to thyroid cancer in a prospective cohort of 484,326 United States men and women, followed from 1995/1996 to 2003. During 3,490,300 person-years of follow-up, we documented 352 newly incident cases of thyroid cancer. The multivariate relative risks (RR) of thyroid cancer for BMI values of 18.5–24.9 (reference), 25.0–29.9 and ≥30 kg m−2 were 1.0, 1.27 and 1.39 [95% confidence interval (CI) = 1.05–1.85]. Adiposity predicted papillary thyroid cancers (RR comparing extreme BMI categories = 1.47; 95% CI = 1.03–2.10) and, based on small numbers, suggestively predicted follicular thyroid cancers (RR = 1.49; 95% CI = 0.79–2.82) and anaplastic thyroid cancers (RR = 5.80; 95% CI = 0.99–34.19). No relation with BMI was noted for medullary thyroid cancers (RR = 0.97; 95% CI = 0.27–3.43). The positive relation of BMI to total thyroid cancer was evident for men but not for women. However, the test of interaction (p = 0.463) indicated no statistically significant gender difference. Physical activity was unassociated with thyroid cancer. The RRs of total thyroid cancer for low (reference), intermediate, and high level of physical activity were 1.0, 1.01 and 1.01 (95% CI = 0.76–1.34, p for trend = 0.931), respectively. Our results support an adverse effect of adiposity on risk for developing total and papillary, and possibly follicular thyroid cancers. Based on only 15 cases, adiposity was unrelated to medullary thyroid cancers. Physical activity was unrelated to total thyroid cancer.

Meat and components of meat and the risk of bladder cancer in the NIH-AARP Diet and Health Study

Abstract: BACKGROUND: Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs). The authors comprehensively investigated the association between meat and meat components and bladder cancer. METHODS: During 7 years of follow-up, 854 transitional cell bladder-cancer cases were identified among 300,933 men and women who had completed a validated food-frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. The authors estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat by using quantitative databases of measured values. Total dietary nitrate and nitrite were calculated based on literature values. RESULTS: The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth quintile compared with first quintile, 1.22; 95% CI, 0.96-1.54; Ptrend = .07) and the HCA 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) (HR, 1.19; 95% CI, 0.95-1.48; Ptrend = .06) conferred a borderline statistically significant increased risk of bladder cancer. Positive associations were observed in the top quintile for total dietary nitrite (HR, 1.28; 95% CI, 1.02-1.61; Ptrend = .06) and nitrate plus nitrite intake from processed meat (HR, 1.29; 95% CI, 1.00-1.67; Ptrend = .11). CONCLUSIONS: These findings provided modest support for an increased risk of bladder cancer with total dietary nitrite and nitrate plus nitrite from processed meat. Results also suggested a positive association between red meat and PhIP and bladder carcinogenesis. Cancer 2010. © 2010 American Cancer Society.

Intakes of vitamins A, C, and E and use of multiple vitamin supplements and risk of colon cancer: a pooled analysis of prospective cohort studies

Abstract: Objective To evaluate the associations between intakes of vitamins A, C, and E and risk of colon cancer.

The association of menstrual and reproductive factors with upper gastrointestinal tract cancers in the NIH-AARP cohort.

Abstract: BACKGROUND: In most populations, incidence rates of upper gastrointestinal (UGI) tract cancers (head and neck, esophagus, and stomach) are higher among men than among women. Established risk factors do not appear to explain these differences, suggesting a possible role for sex hormones. METHODS: 201,506 women of the NIH-AARP Diet and Health cohort completed a questionnaire in 1995-1996. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models. RESULTS: During follow-up through 2003, 162 incident adenocarcinomas (ACs; esophagus, N = 25, and stomach, N = 137) and 353 incident squamous cell carcinomas (SCCs; head and neck, n = 297, and esophagus, N = 56) occurred. Among examined exposures, older age at menopause was associated inversely with SCC (Ptrend across categories = .013) but not AC (Ptrend = .501). Use of menopausal hormone therapy (MHT) was significantly associated with lower risk of SCC (hazard ratio [HR] = 0.77, 0.62-0.96) and nonsignificantly associated with lower risk of AC (HR = 0.81, 0.59-1.12). A subset (N = 127,386) of the cohort completed a more detailed MHT questionnaire a year after baseline. In 74,372 women with intact uteri, ever use of estrogen-progestin MHT conferred 0.47 (0.30-0.75) times the risk for SCC and 0.52 (0.26-1.07) times the risk for ACC. In 51,515 women with a hysterectomy before baseline, we found no associations between use of estrogen MHT and AC or SCC. CONCLUSIONS: Higher estrogen and progesterone levels may be related inversely to UGI cancers and in this way help explain lower incidence rates in women compared with men. Cancer 2010. © 2010 American Cancer Society.

Diet, Lifestyle, and Acute Myeloid Leukemia in the NIH–AARP Cohort

Abstract: The relation between diet, lifestyle, and acute myeloid leukemia was assessed in a US cohort of 491,163 persons from the NIH–AARP Diet and Health Study (1995–2003). A total of 338 incident cases of acute myeloid leukemia were ascertained. Multivariate Cox models were utilized to estimate hazard ratios and 95% confidence intervals. Compared with those for never smokers, hazard ratios were 1.29 (95% confidence interval: 0.95, 1.75), 1.79 (95% confidence interval: 1.32, 2.42), 2.42 (95% confidence interval: 1.63, 3.57), and 2.29 (85% confidence interval: 1.38, 3.79) for former smokers who smoked ≤1 or >1 pack/day and for current smokers who smoked ≤1 or >1 pack/day, respectively. Higher meat intake was associated with an increased risk of acute myeloid leukemia (hazard ratio = 1.45, 95% confidence interval: 1.02, 2.07 for the fifth vs. first quintile; P for trend = 0.06); however, there were no clear effects of meat-cooking method or doneness level. Individuals who did not drink coffee appeared to have a higher risk of acute myeloid leukemia than those who drank various quantities of coffee. Neither fruit nor vegetable intake was associated with acute myeloid leukemia. This large prospective study identified smoking and meat intake as risk factors for acute myeloid leukemia.

Mineral Intake and Lung Cancer Risk in the NIH-American Association of Retired Persons Diet and Health Study

Abstract: Background: Using data from a case-control study, we previously reported that low dietary intakes of magnesium (Mg), iron (Fe), zinc (Zn), copper (Cu), but not selenium (Se) and calcium (Ca), were associated with increased lung cancer risk. Due to dietary recall bias in case-control studies, our objective was to assess whether these findings hold in a prospective cohort study. Methods: We analyzed data from the NIH-American Association of Retired Persons Diet and Health study of 482,875 subjects (288,257 men and 194,618 women) who were cancer-free and completed a food frequency questionnaire at enrollment between 1995 and 2003. Cox proportional hazards models were computed to estimate the relative risk adjusted for potential confounders. Results: During a mean follow-up of 7 years, 7,052 lung cancer cases were identified. For all subjects, we observed no significant associations between total (diet + supplement) Ca, Mg, Fe, Cu, Se, and Zn intakes and lung cancer risk. Total Ca intake was protective ( P trend < 0.05) for current smokers and subjects with adenocarcinomas. Total Mg intake increased risk ( P trend < 0.05) in men and current smokers. Total Fe intake was inversely associated with risk in women ( P trend < 0.01). For dietary minerals, Mg increased risk ( P trend < 0.05) in all subjects, among men and current smokers. Increased dietary Ca intake reduced risk in women ( P trend = 0.05). Dietary Fe decreased risk in all subjects and among women ( P trend < 0.05). Mineral intake from supplements did not affect lung cancer risk. Conclusions: Dietary minerals are risk factors for lung cancer. Impact: Dietary mineral consumption may influence lung cancer risk, but the associations differ by type of mineral and population subgroups. Cancer Epidemiol Biomarkers Prev; 19(8); 1976–83. ©2010 AACR.

Diabetes and risk of incident colorectal cancer in a prospective cohort of women

Abstract: Objective To determine whether accounting for the time dynamics of diabetes exposure will change the risk estimates for colorectal cancer.

Gains in Statistical Power From Using a Dietary Biomarker in Combination With Self-reported Intake to Strengthen the Analysis of a Diet-Disease Association: An Example From CAREDS

Abstract: A major problem in detecting diet-disease associations in nutritional cohort studies is measurement error in self-reported intakes, which causes loss of statistical power. The authors propose using biomarkers correlated with dietary intake to strengthen analyses of diet-disease hypotheses and to increase statistical power. They consider combining self-reported intakes and biomarker levels using principal components or a sum of ranks and relating the combined measure to disease in conventional regression analyses. They illustrate their method in a study of the inverse association of dietary lutein plus zeaxanthin with nuclear cataracts, using serum lutein plus zeaxanthin as the biomarker, with data from the Carotenoids in Age-Related Eye Disease Study (United States, 2001-2004). This example demonstrates that the combined measure provides higher statistical significance than the dietary measure or the serum measure alone, and it potentially provides sample savings of 8%-53% over analysis with dietary intake alone and of 6%-48% over analysis with serum level alone, depending on the definition of the outcome variable and the choice of confounders entered into the regression model. The authors conclude that combining appropriate biomarkers with dietary data in a cohort can strengthen the investigation of diet-disease associations by increasing the statistical power to detect them.

Serum Adiponectin, Leptin, C-Peptide, Homocysteine, and Colorectal Adenoma Recurrence in the Polyp Prevention Trial

Abstract: Background: Serum adiponectin, leptin, C-peptide, and homocysteine are indicators for obesity, hyperinsulinemia, and chronic inflammation, which have all been associated with colorectal cancer. Aims: To determine whether serum adiponectin, leptin, C-peptide, and homocysteine are associated with fat, fiber, fruit and vegetable, flavonol, or dry bean intake and colorectal adenoma recurrence. Methods: Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (95% CI) for adenoma recurrence in 627 participants from the control arm of the Polyp Prevention Trial, a 4-year trial that examined the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence. Results: Serum concentrations of C-peptide and homocysteine were inversely related to fiber, fruit and vegetable, and flavonol intake and positively related to percentage of calories from fat (all P trend ≤0.01). High homocysteine concentrations were associated with any (4th versus 1st quartile: OR, 2.26; 95% CI, 1.30-3.94) and more than one adenoma recurrence (OR, 2.11; 95% CI, 1.01-4.40). Individuals in the highest, versus lowest, tertile of serum leptin concentration had a decreased risk of advanced adenoma recurrence (OR, 0.22; 95% CI, 0.06-0.79). Conclusion: Our results suggest that serum homocysteine may serve as an indicator of dietary exposure, including a low-fat and high-fiber, high-fruit and vegetable, and high-flavonol diet, as well as colorectal adenoma recurrence. Impact: Discovering biomarkers that are both modifiable and can predict cancer risk is critical. We identified serum homocysteine as a novel indicator that is modified by diet and predicts risk of adenoma recurrence. Cancer Epidemiol Biomarkers Prev; 19(6); 1441–52. ©2010 AACR.

Effect of smoking status on total energy expenditure.

Abstract: Individuals who smoke generally have a lower body mass index (BMI) than nonsmokers. The relative roles of energy expenditure and energy intake in maintaining the lower BMI, however, remain controversial. We tested the hypothesis that current smokers have higher total energy expenditure than never smokers in 308 adults aged 40-69 years old of which 47 were current smokers. Energy expenditure was measured by doubly labeled water during a two week period in which the subjects lived at home and performed their normal activities. Smoking status was determined by questionnaire. There were no significant differences in mean BMI (mean ± SD) between smokers and never smokers for either males (27.8+5.1 kg/m2 vs. 27.5+4.0 kg/m2) or females (26.5+5.3 kg/m2 vs. 28.1+6.6 kg/m2), although the difference in females was of similar magnitude to previous reports. Similarly, total energy expenditure of male smokers (3069+764 kcal/d) was not significantly different from that of never smokers (2854+468 kcal/d), and that of female smokers (2266+387 kcal/d) was not different from that of never smokers (2330+415 kcal/d). These findings did not change after adjustment for age, fat-free mass and self-reported physical activity. Using doubly labeled water, we found no evidence of increased energy expenditure among smokers, however, it should be noted that BMI differences in this cohort also did not differ by smoking status.

Abstract B97: Alcoholic beverages and prostate cancer in a prospective U.S. cohort study

Abstract: Higher alcohol consumption has been shown to be a risk factor for many cancers, yet despite a number of investigations, its relation to prostate cancer has not been established. We investigated the association between alcohol consumption and risk of prostate cancer in a large prospective study of dietary and environmental cancer risk factors among 294,707 men aged 50–71 years old upon enrollment in 1995–1996. Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (95% CI) were adjusted for several characteristics including age, race, body mass index, physical activity, family history of prostate cancer, and PSA and DRE testing. There were 15,327 nonadvanced and 1,900 advanced incident prostate cancers identified through 2003 and 514 men died of prostate cancer through 2005. Risk of nonadvanced prostate cancer was 25% higher in men consuming 6 or more drinks per day (HR= 1.25, 95% CI: 1.13 – 1.37), 19% higher in men consuming between 3 and 6 drinks per day (HR= 1.19, 95% CI: 1.11 – 1.29), and 6% higher in men consuming up to 3 drinks per day compared to nondrinkers (HR= 1.06, 95% CI: 1.00 – 1.12). The lowest risk of nonadvanced prostate cancer was seen among nondrinkers. We observed no association between alcohol intake and advanced cancers and a possible association against fatal prostate cancer among a small number of heavy drinkers with 6+ drinks daily (HR= 0.45, 95% CI: 0.25 – 0.81). There were similar associations observed for all types of alcoholic beverages (i.e., wine, beer, liquor). In this large prospective study, we found that alcohol consumption modestly increased the risk of nonadvanced prostate cancers. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B97.