Betsy Rolland

Association between Body-Mass Index and Risk of Death in More Than 1 Million Asians

BACKGROUND Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin. METHODS We performed pooled analyses to evaluate the association between BMI and the risk of death among more than 1.1 million persons recruited in 19 cohorts in Asia. The analyses included approximately 120,700 deaths that occurred during a mean follow-up period of 9.2 years. Cox regression models were used to adjust for confounding factors. RESULTS In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range--by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI. CONCLUSIONS Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seen among East Asians but not among Indians and Bangladeshis.

Body-mass index and all-cause mortality: Individual-participant-data meta-analysis of 239 prospective studies in four continents.

Summary Background Overweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant data meta-analyses of prospective studies of body-mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding pre-existing disease and the first 5 years of follow-up. Methods Of 10 625 411 participants in Asia, Australia and New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13·7 years, IQR 11·4–14·7), 3 951 455 people in 189 studies were never-smokers without chronic diseases at recruitment who survived 5 years, of whom 385 879 died. The primary analyses are of these deaths, and study, age, and sex adjusted hazard ratios (HRs), relative to BMI 22·5–<25·0 kg/m2. Findings All-cause mortality was minimal at 20·0–25·0 kg/m2 (HR 1·00, 95% CI 0·98–1·02 for BMI 20·0–<22·5 kg/m2; 1·00, 0·99–1·01 for BMI 22·5–<25·0 kg/m2), and increased significantly both just below this range (1·13, 1·09–1·17 for BMI 18·5–<20·0 kg/m2; 1·51, 1·43–1·59 for BMI 15·0–<18·5) and throughout the overweight range (1·07, 1·07–1·08 for BMI 25·0–<27·5 kg/m2; 1·20, 1·18–1·22 for BMI 27·5–<30·0 kg/m2). The HR for obesity grade 1 (BMI 30·0–<35·0 kg/m2) was 1·45, 95% CI 1·41–1·48; the HR for obesity grade 2 (35·0–<40·0 kg/m2) was 1·94, 1·87–2·01; and the HR for obesity grade 3 (40·0–<60·0 kg/m2) was 2·76, 2·60–2·92. For BMI over 25·0 kg/m2, mortality increased approximately log-linearly with BMI; the HR per 5 kg/m2 units higher BMI was 1·39 (1·34–1·43) in Europe, 1·29 (1·26–1·32) in North America, 1·39 (1·34–1·44) in east Asia, and 1·31 (1·27–1·35) in Australia and New Zealand. This HR per 5 kg/m2 units higher BMI (for BMI over 25 kg/m2) was greater in younger than older people (1·52, 95% CI 1·47–1·56, for BMI measured at 35–49 years vs 1·21, 1·17–1·25, for BMI measured at 70–89 years; pheterogeneity<0·0001), greater in men than women (1·51, 1·46–1·56, vs 1·30, 1·26–1·33; pheterogeneity<0·0001), but similar in studies with self-reported and measured BMI. Interpretation The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents. This finding supports strategies to combat the entire spectrum of excess adiposity in many populations. Funding UK Medical Research Council, British Heart Foundation, National Institute for Health Research, US National Institutes of Health.

Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium

Objective To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians. Design Pooled analyses of 20 prospective cohorts in Asia, including data from 835 082 east Asians and 289 815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability. Setting General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh). Participants 1 124 897 men and women (mean age 53.4 years at baseline). Main outcome measures Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes. Results 49 184 cardiovascular deaths (40 791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12). Conclusions Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.

Body Mass Index and Diabetes in Asia: A Cross-Sectional Pooled Analysis of 900,000 Individuals in the Asia Cohort Consortium

Background The occurrence of diabetes has greatly increased in low- and middle-income countries, particularly in Asia, as has the prevalence of overweight and obesity; in European-derived populations, overweight and obesity are established causes of diabetes. The shape of the association of overweight and obesity with diabetes risk and its overall impact have not been adequately studied in Asia. Methods and Findings A pooled cross-sectional analysis was conducted to evaluate the association between baseline body mass index (BMI, measured as weight in kg divided by the square of height in m) and self-reported diabetes status in over 900,000 individuals recruited in 18 cohorts from Bangladesh, China, India, Japan, Korea, Singapore and Taiwan. Logistic regression models were fitted to calculate cohort-specific odds ratios (OR) of diabetes for categories of increasing BMI, after adjustment for potential confounding factors. OR were pooled across cohorts using a random-effects meta-analysis. The sex- and age-adjusted prevalence of diabetes was 4.3% in the overall population, ranging from 0.5% to 8.2% across participating cohorts. Using the category 22.5–24.9 Kg/m2 as reference, the OR for diabetes spanned from 0.58 (95% confidence interval [CI] 0.31, 0.76) for BMI lower than 15.0 kg/m2 to 2.23 (95% CI 1.86, 2.67) for BMI higher than 34.9 kg/m2. The positive association between BMI and diabetes prevalence was present in all cohorts and in all subgroups of the study population, although the association was stronger in individuals below age 50 at baseline (p-value of interaction<0.001), in cohorts from India and Bangladesh (p<0.001), in individuals with low education (p-value 0.02), and in smokers (p-value 0.03); no differences were observed by gender, urban residence, or alcohol drinking. Conclusions This study estimated the shape and the strength of the association between BMI and prevalence of diabetes in Asian populations and identified patterns of the association by age, country, and other risk factors for diabetes.

Meat intake and cause-specific mortality: a pooled analysis of Asian prospective cohort studies

BACKGROUND Total or red meat intake has been shown to be associated with a higher risk of mortality in Western populations, but little is known of the risks in Asian populations. OBJECTIVE We examined temporal trends in meat consumption and associations between meat intake and all-cause and cause-specific mortality in Asia. DESIGN We used ecological data from the United Nations to compare country-specific meat consumption. Separately, 8 Asian prospective cohort studies in Bangladesh, China, Japan, Korea, and Taiwan consisting of 112,310 men and 184,411 women were followed for 6.6 to 15.6 y with 24,283 all-cause, 9558 cancer, and 6373 cardiovascular disease (CVD) deaths. We estimated the study-specific HRs and 95% CIs by using a Cox regression model and pooled them by using a random-effects model. RESULTS Red meat consumption was substantially lower in the Asian countries than in the United States. Fish and seafood consumption was higher in Japan and Korea than in the United States. Our pooled analysis found no association between intake of total meat (red meat, poultry, and fish/seafood) and risks of all-cause, CVD, or cancer mortality among men and women; HRs (95% CIs) for all-cause mortality from a comparison of the highest with the lowest quartile were 1.02 (0.91, 1.15) in men and 0.93 (0.86, 1.01) in women. CONCLUSIONS Ecological data indicate an increase in meat intake in Asian countries; however, our pooled analysis did not provide evidence of a higher risk of mortality for total meat intake and provided evidence of an inverse association with red meat, poultry, and fish/seafood. Red meat intake was inversely associated with CVD mortality in men and with cancer mortality in women in Asian countries.

Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine—a pooled analysis of over 500 000 subjects in the Asia Cohort Consortium

BACKGROUND The evidence for a role of tobacco smoking, alcohol drinking, and body mass index (BMI) in the etiology of small intestine cancer is based mainly on case-control studies from Europe and United States. SUBJECTS AND METHODS We harmonized the data across 12 cohort studies from mainland China, Japan, Korea, Singapore, and Taiwan, comprising over 500,000 subjects followed for an average of 10.6 years. We calculated hazard ratios (HRs) for BMI and (only among men) tobacco smoking and alcohol drinking. RESULTS A total of 134 incident cases were observed (49 adenocarcinoma, 11 carcinoid, 46 other histologic types, and 28 of unknown histology). There was a statistically non-significant trend toward increased HR in subjects with high BMI [HR for BMI>27.5 kg/m2, compared with 22.6-25.0, 1.50; 95% confidence interval (CI) 0.76-2.96]. No association was suggested for tobacco smoking; men drinking>400 g of ethanol per week had an HR of 1.57 (95% CI 0.66-3.70), compared with abstainers. CONCLUSIONS Our study supports the hypothesis that elevated BMI may be a risk factor for small intestine cancer. An etiologic role of alcohol drinking was suggested. Our results reinforce the existing evidence that the epidemiology of small intestine cancer resembles that of colorectal cancer.

Associations of Body Mass Index, Smoking, and Alcohol Consumption With Prostate Cancer Mortality in the Asia Cohort Consortium

Many potentially modifiable risk factors for prostate cancer are also associated with prostate cancer screening, which may induce a bias in epidemiologic studies. We investigated the associations of body mass index (weight (kg)/height (m)(2)), smoking, and alcohol consumption with risk of fatal prostate cancer in Asian countries where prostate cancer screening is not widely utilized. Analysis included 18 prospective cohort studies conducted during 1963-2006 across 6 countries in southern and eastern Asia that are part of the Asia Cohort Consortium. Body mass index, smoking, and alcohol intake were determined by questionnaire at baseline, and cause of death was ascertained through death certificates. Analysis included 522,736 men aged 54 years, on average, at baseline. During 4.8 million person-years of follow-up, there were 634 prostate cancer deaths (367 prostate cancer deaths across the 11 cohorts with alcohol data). In Cox proportional hazards analyses of all cohorts in the Asia Cohort Consortium, prostate cancer mortality was not significantly associated with obesity (body mass index >25: hazard ratio (HR) = 1.08, 95% confidence interval (CI): 0.85, 1.36), ever smoking (HR = 1.00, 95% CI: 0.84, 1.21), or heavy alcohol intake (HR = 1.00, 95% CI: 0.74, 1.35). Differences in prostate cancer screening and detection probably contribute to differences in the association of obesity, smoking, or alcohol intake with prostate cancer risk and mortality between Asian and Western populations and thus require further investigation.

Association of body mass index and risk of death from pancreas cancer in Asians: Findings from the Asia Cohort Consortium

We aimed to examine the association between BMI and the risk of death from pancreas cancer in a pooled analysis of data from the Asia Cohort Consortium. The data for this pooled analysis included 883 529 men and women from 16 cohort studies in Asian countries. Cox proportional-hazards models were used to estimate the hazard ratios and 95% confidence intervals for pancreas cancer mortality in relation to BMI. Seven predefined BMI categories (<18.5, 18.5–19.9, 20.0–22.4, 22.5–24.9, 25.0–27.4, 27.5–29.9, ≥30) were used in the analysis, with BMI of 22.5–24.9 serving as the reference group. The multivariable analyses were adjusted for known risk factors, including age, smoking, and a history of diabetes. We found no statistically significant overall association between each BMI category and the risk of death from pancreas cancer in all Asians, and obesity was unrelated to the risk of mortality in both East Asians and South Asians. Age, smoking, and a history of diabetes did not modify the association between BMI and the risk of death from pancreas cancer. In planned subgroup analyses among East Asians, an increased risk of death from pancreas cancer among those with a BMI less than 18.5 was observed for individuals with a history of diabetes; hazard ratio=2.01 (95% confidence interval: 1.01–4.00) (P for interaction=0.07). The data do not support an association between BMI and the risk of death from pancreas cancer in these Asian populations.

Population-based precision cancer screening: a symposium on evidence, epidemiology, and next steps

Precision medicine, an emerging approach for disease treatment that takes into account individual variability in genes, environment, and lifestyle, is under consideration for preventive interventions, including cancer screening. On September 29, 2015, the National Cancer Institute sponsored a symposium entitled “Precision Cancer Screening in the General Population: Evidence, Epidemiology, and Next Steps”. The goal was two-fold: to share current information on the evidence, practices, and challenges surrounding precision screening for breast, cervical, colorectal, lung, and prostate cancers, and to allow for in-depth discussion among experts in relevant fields regarding how epidemiology and other population sciences can be used to generate evidence to inform precision screening strategies. Attendees concluded that the strength of evidence for efficacy and effectiveness of precision strategies varies by cancer site, that no one research strategy or methodology would be able or appropriate to address the many knowledge gaps in precision screening, and that issues surrounding implementation must be researched as well. Additional discussion needs to occur to identify the high priority research areas in precision cancer screening for pertinent organs and to gather the necessary evidence to determine whether further implementation of precision cancer screening strategies in the general population would be feasible and beneficial. Cancer Epidemiol Biomarkers Prev; 25(11); 1449–55. ©2016 AACR.

Coordinating Centers in Cancer Epidemiology Research: the Asia Cohort Consortium Coordinating Center

Although it is tacitly recognized that a good coordinating center (CC) is essential to the success of any multisite collaborative project, very little study has been done on what makes a CC successful, why some CCs fail, or how to build a CC that meets the needs of a given project. Moreover, very little published guidance is available, as few CCs outside the clinical trial realm write about their work. The Asia Cohort Consortium (ACC) is a collaborative cancer epidemiology research project that has made strong scientific and organizational progress over the past 3 years by focusing its CC on the following activities: collaboration development; operations management; statistical and data management; and communications infrastructure and tool development. Our hope is that, by sharing our experience building the ACC CC, we can begin a conversation about what it means to run a CC for multi-institutional collaboration in cancer epidemiology, help other collaborative projects solve some of the issues associated with collaborative research, and learn from others. Cancer Epidemiol Biomarkers Prev; 20(10); 2115–9. ©2011 AACR.