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BackgroundThe prevalence of class III obesity (body mass index [BMI]≥40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity.Methods and findingsIn a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19-83 y at baseline, classified as obese class III (BMI 40.0-59.9 kg/m2) compared with those classified as normal weight (BMI 18.5-24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976-2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40-44.9, 45-49.9, 50-54.9, and 55-59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7-7.3), 8.9 (95% CI: 7.4-10.4), 9.8 (95% CI: 7.4-12.2), and 13.7 (95% CI: 10.5-16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report.ConclusionsClass III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight. Please see later in the article for the Editors' Summary.

The role of lifestyle risk factors in prostate cancer risk remains elusive despite a large number of epidemiologic studies. In a pooled analysis of data from South and East Asian countries published in this issue, Fowke et al. (Am J Epidemiol. 2015;182(5):381-389) found no evidence for an association between prostate cancer mortality and obesity, alcohol, or smoking. Prostate cancer screening is very uncommon in these countries, and previous evidence for associations with lifestyle factors comes primarily from studies carried out in North America, where screening is very common. Fowke et al. concluded that screening biases are likely to explain the differences in study results. In this commentary, we discuss the potential influence of population-based cancer screening programs in estimates of association from epidemiologic studies. This highlights the importance of carefully considering the impact of screening in the analysis and interpretation of results, in order to advance our understanding of the etiology of cancers that can be detected by screening. [ABSTRACT FROM AUTHOR]

Pooled analyses among whites and East Asians have demonstrated positive associations between all-cause mortality and body mass index (BMI), but studies of African Americans have yielded less consistent results. We examined the association between BMI and all-cause mortality in a sample of African Americans pooled from seven prospective cohort studies: NIH-AARP, 1995–2009; Adventist Health Study 2, 2002–2008; Black Women's Health Study, 1995–2009; Cancer Prevention Study II, 1982–2008; Multiethnic Cohort Study, 1993–2007; Prostate, Lung, Colorectal and Ovarian Screening Trial, 1993–2009; Southern Community Cohort Study, 2002–2009. 239,526 African Americans (including 100,175 never smokers without baseline heart disease, stroke, or cancer), age 30–104 (mean 52) and 71% female, were followed up to 26.5 years (mean 11.7). Hazard ratios (HR) and 95% confidence intervals (CI) for mortality were derived from multivariate Cox proportional hazards models. Among healthy, never smokers (11,386 deaths), HRs (CI) for BMI 25–27.4, 27.5–29.9, 30–34.9, 35–39.9, 40–49.9, and 50–60 kg/m2 were 1.02 (0.92–1.12), 1.06 (0.95–1.18), 1.32 (1.18–1.47), 1.54 (1.29–1.83), 1.93 (1.46–2.56), and 1.93 (0.80–4.69), respectively among men and 1.06 (0.99–1.15), 1.15 (1.06–1.25), 1.24 (1.15–1.34), 1.58 (1.43–1.74), 1.80 (1.60–2.02), and 2.31 (1.74–3.07) respectively among women (reference category 22.5–24.9). HRs were highest among those with the highest educational attainment, longest follow-up, and for cardiovascular disease mortality. Obesity was associated with a higher risk of mortality in African Americans, similar to that observed in pooled analyses of whites and East Asians. This study provides compelling evidence to support public health efforts to prevent excess weight gain and obesity in African Americans. [ABSTRACT FROM AUTHOR]

Smoking and diabetes are the only established risk factors for pancreatic cancer. Findings from recent studies suggest that obesity may also be associated with an increased risk of pancreatic cancer, but several earlier studies were less conclusive. We examined this relationship in a meta-analysis of published data. Six case-control and eight cohort studies involving 6391 cases of pancreatic cancer were identified from a computer-based literature search from 1966 to 2003. The relative risk per unit increase in body mass index was estimated for each of the studies from the published data. In a random effects model, the summary relative risk per unit increase in body mass index was 1.02 (95% CI: 1.01-1.03). There was some evidence of heterogeneity between the studies' results (P = 0.1). The summary relative risk estimates were slightly higher for studies that had adjusted for smoking and for case-control studies that had not used proxy respondents. The estimated per unit increase in body mass index would translate into a relative risk of 1.19 (95% CI: 1.10-1.29) for obese people (30 kgm[SUP-2]) compared to people with a normal body weight (22 kg m[SUP-2]). These results provide evidence that the risk of pancreatic cancer may be weakly associated with obesity. However, the small magnitude of the summary risk means the possibility of confounding cannot be excluded. [ABSTRACT FROM AUTHOR]

Background: Body mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. Design: We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n= 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18-21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Results: Higher waist-to-hip ratio (HR = 1.09, 95% CI 1.02-1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00-1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11-1.25 per 5 kg/m²), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m ², HR = 1.36, 95% CI 1.20-1.55 for BMI 25.0 < 27.5 kg/m², HR = 1.48, 95% CI 1.20-1.84 for BMI 27.5 to <30 kg/m², HR = 1.43, 95% CI 1.11-1.85 for BMI ≥30 kg/m²). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01-1.10 per 5 kg/m²). Conclusions: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in in uencing pancreat-ic cancer mortality risk later in life. [ABSTRACT FROM AUTHOR]