Faculty Bibliography

OBJECTIVE:To study the association of educational level and risk of death from all causes, cardiovascular disease (CVD) and cancer among Asian populations. DESIGN/METHODS:A pooled analysis of 15 population-based cohort studies. SETTING AND PARTICIPANTS/METHODS:694 434 Asian individuals from 15 prospective cohorts within the Asia Cohort Consortium. INTERVENTIONS/METHODS:None. MAIN OUTCOME MEASURES/METHODS:HRs and 95% CIs for all-cause mortality, as well as for CVD-specific mortality and cancer-specific mortality. RESULTS:<0.01). The pattern of the association among East Asians and South Asians was similar compared with ≤primary education; HR (95% CI) for all-cause mortality associated with ≥university education was 0.72 (0.63 to 0.81) among 539 724 East Asians (Chinese, Japanese and Korean) and 0.61 (0.54 to 0.69) among 154 710 South Asians (Indians and Bangladeshis). CONCLUSION/CONCLUSIONS:Higher educational level was associated with substantially lower risk of death among Asian populations.

Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index, waist circumference, hip circumference, waist-to-hip and waist-to-height ratios. Hazard ratios (HR) and 95% confidence intervals (95%CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m2 increase in body mass index there were risk increases for GBC (HR: 1.27 [95% CI: 1.19, 1.36]), IHBDC (HR: 1.32 [95% CI: 1.21, 1.45]), and EHBDC (HR: 1.13 [95% CI: 1.03, 1.23]), but not AVC (HR: 0.99 [95% CI: 0.88, 1.11]). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers.

This paper presents the results of the literature review conducted for the working group topic on inflammation, infection, exposure, and the human microbiome. Infection and chronic inflammation can elevate risk for cardiovascular disease and cancer. Environmental exposures common among South Asian (SA) subgroups, such as arsenic exposure among Bangladeshis and particulate matter air pollution among taxi drivers, also pose risks. This review explores the effects of exposure to arsenic and particulate matter, as well as other infections common among SAs, including human papillomavirus (HPV) and hepatitis B/C infection. Emerging research on the human microbiome, and the effect of microbiome changes on obesity and diabetes risk among SAs are also explored.

To examine how urban form shapes physical activity and health over time, a measure of neighborhood walkability is needed that can be linked to cohort studies with participants living across the United States (U.S.) that have been followed over the past decades. The Built Environment and Health-Neighborhood Walkability Index (BEH-NWI), a measure of neighborhood walkability that can be calculated for communities across the United States between 1990 and 2015, was conceptualized, developed, and tested using data from the New York City Tri-State Area. BEH-NWI measures were created for 1990 and 2010 using historical data on population density, street intersection density, density of rail stops, and density of pedestrian trip generating/supporting establishments. BEH-NWI scores were calculated for 1-km buffers around the 1990 residences of NYU Women's Health Study (NYUWHS) participants and NYC Department of Health and Mental Hygiene's Physical Activity and Transit (PAT) survey participants enrolled in 2011. Higher neighborhood BEH-NWI scores were significantly associated with greater self-reported walking per week (+ 0.31 MET-hours/week per unit BEH-NWI, 95% CI 0.23, 0.36) and lower body mass index (- 0.17 BMI units per unit BEH-NWI, 95% - 0.23, - 0.12) among NYUWHS participants. Higher neighborhood BEH-NWI scores were associated with significantly higher accelerometer-measured physical activity among PAT survey participants (39% more minutes of moderate-intensity equivalent activity/week across the interquartile range of BEH-NWI, 95% CI 21%, 60%). The BEH-NWI can be calculated using historical data going back to 1990, and BEH-NWI scores predict BMI, weekly walking, and physical activity in two NYC area datasets.

Our objective was to investigate the relationship between the gut microbiota and anthropometric measurements among 248 participants from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Our cohort represents a unique population that allows for the investigation of the gut microbiota and anthropometric measurements in lean individuals. We measured height, weight, arm, thigh, hip, and waist circumferences, and collected fecal samples. Microbial DNA was extracted from the stool samples and sequenced by 16S rRNA gene sequencing. We examined associations between relative abundance of individual bacterial taxa from phylum to genus levels and anthropometric measurements. We found that higher BMI, mid-upper arm circumference, waist circumference, and waist-to-hip ratio were associated with a lower alpha diversity of fecal bacteria. Relative abundance of the genus Oscillospira and the family S24-7 were inversely related to all measurements after correction for multiple testing. Relative abundance of genus Acidaminococcus and family Ruminococcaceae were also associated with several measurements. The positive associations of the genus Acidaminococcus with BMI, as well as waist and hip circumferences, were stronger in women than in men. Our data in this lean Bangladeshi population found a correlation between Oscillospira and leanness, as measured using multiple anthropometric measures.

Importance/UNASSIGNED:Asia is home to the largest diabetic populations in the world. However, limited studies have quantified the association of diabetes with all-cause and cause-specific mortality in Asian populations. Objectives/UNASSIGNED:To evaluate the association of diabetes with all-cause and cause-specific mortality in Asia and to investigate potential effect modifications of the diabetes-mortality associations by participants' age, sex, education level, body mass index, and smoking status. Design, Setting, and Participants/UNASSIGNED:This pooled analysis incorporated individual participant data from 22 prospective cohort studies of the Asia Cohort Consortium conducted between 1963 and 2006. A total of 1 002 551 Asian individuals (from mainland China, Japan, South Korea, Singapore, Taiwan, India, and Bangladesh) were followed up for more than 3 years. Cohort-specific hazard ratios and 95% confidence intervals for all-cause and cause-specific mortality were estimated using Cox regression models and then pooled using random-effects meta-analysis. Analysis was conducted between January 10, 2018, and August 31, 2018. Exposures/UNASSIGNED:Doctor-diagnosed diabetes, age, sex, education level, body mass index, and smoking status. Main Outcomes and Measures/UNASSIGNED:All-cause and cause-specific mortality. Results/UNASSIGNED:Of 1 002 551 participants (518 537 [51.7%] female; median [range] age, 54.0 [30.0-98.0] years), 148 868 deaths were ascertained during a median (range) follow-up of 12.6 (3.0-38.9) years. The overall prevalence of diabetes reported at baseline was 4.8% for men and 3.6% for women. Patients with diabetes had a 1.89-fold risk of all-cause death compared with patients without diabetes (hazard ratio [HR], 1.89; 95% CI, 1.74-2.04), with the highest relative risk of death due to diabetes itself (HR, 22.8; 95% CI, 18.5-28.1), followed by renal disease (HR, 3.08; 95% CI, 2.50-3.78), coronary heart disease (HR, 2.57; 95% CI, 2.19-3.02), and ischemic stroke (HR, 2.15; 95% CI, 1.85-2.51). The adverse diabetes-mortality associations were more evident among women (HR, 2.09; 95% CI, 1.89-2.32) than among men (HR, 1.74; 95% CI, 1.62-1.88) (P for interaction < .001) and more evident among adults aged 30 to 49 years (HR, 2.43; 95% CI, 2.08-2.84) than among adults aged 70 years and older (HR, 1.51; 95% CI, 1.40-1.62) (P for interaction < .001). A similar pattern of association was found between diabetes and cause-specific mortality, with significant variations noted by sex and age. Conclusions and Relevance/UNASSIGNED:This study found that diabetes was associated with increased risk of death from several diseases among Asian populations. Development and implementation of diabetes management programs are urgently needed to reduce the burden of diabetes in Asia.

BACKGROUND:Emerging data suggest that inorganic arsenic exposure and gut microbiome are associated with the risk of cardiovascular disease. The gut microbiome may modify disease risk associated with arsenic exposure. Our aim was to examine the inter-relationships between arsenic exposure, the gut microbiome, and carotid intima-media thickness (IMT)-a surrogate marker for atherosclerosis. METHODS:We recruited 250 participants from the Health Effects of Arsenic Longitudinal Study in Bangladesh, measured IMT and collected fecal samples in year 2015-2016. 16S rRNA gene sequencing was conducted on microbial DNA extracted from the fecal samples. Arsenic exposure was measured using data on arsenic concentration in drinking water wells over time to derive a time-weighted water arsenic index. Multivariable linear regression models were used to test the inter-relationships between arsenic exposure, relative abundance of selected bacterial taxa from phylum to genus levels, and IMT. RESULTS:We identified nominally significant associations between arsenic exposure, measured using either time-weighted water arsenic or urinary arsenic, and the relative abundances of several bacterial taxa from the phylum Tenericutes, Proteobacteria, and Firmicutes. However, none of the associations retained significance after correction for multiple testing. The relative abundances of the family Aeromonadaceae and genus Citrobacter were significantly associated with IMT after correction for multiple testing (P-value = 0.02 and 0.03, respectively). Every 1% increase in the relative abundance of Aeromonadaceae and Citrobacter was related to an 18.2-μm (95% CI: 7.8, 28.5) and 97.3-μm (95% CI: 42.3, 152.3) difference in IMT, respectively. These two taxa were also the only selected family and genus using the LASSO variable selection method. There was a significant interaction between Citrobacter and time-weighted water arsenic in IMT (P for interaction = 0.04). CONCLUSIONS:Our findings suggest a role of Citrobacter in the development of atherosclerosis, especially among individuals with higher levels of arsenic exposure.

BACKGROUND:Concentrations of arsenic (As) are elevated in a large proportion of wells in Bangladesh but are spatially variable even within a village. This heterogeneity can enable exposed households to switch to a nearby well lower in As in response to blanket (area-wide) well As testing. OBJECTIVES/OBJECTIVE:We document the evolution of As exposure in Araihazar, Bangladesh following a blanket well testing and education campaign, as well as the installation of a considerable number of low As community wells. METHODS:area of Araihazar upazila for nearly 12,000 participants enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). We observe changes in participants' well water and urinary As concentrations following interventions to lower their exposure and use logistic regression to determine the factors associated with participants' decisions to switch primary household wells. RESULTS:Urinary As for participants drinking from wells with >100 μg/L As at baseline declined from a mean of 226 μg/L at baseline to 173 μg/L two years later, and further declined to 139 μg/L over 8 years. For comparison, urinary As concentrations for participants drinking from wells with ≤10 μg/L As remained close to 50 μg/L throughout. Whereas the interventions only partially reduced exposure, well status with respect to As was predictive of well-switching decisions for at least a decade after the initial testing. Participants with high-As wells were 7 times more likely to switch wells over the first two years and 1.4-1.8 times more likely to switch wells over the ensuing decade. CONCLUSIONS:Arsenic exposure gradually declined following blanket well testing, an education campaign, and the installation of community wells but remained almost three times higher than for a subgroup of the participants drinking from wells with ≤10 μg/L. In addition, the number of participants with unknown As concentrations in their primary household wells increased substantially over time, indicating the importance of additional well testing as new wells continue to be installed, in addition to other means of reducing As exposure.

BACKGROUND:A number of cohort studies have collected Scope mouthwash samples by mail which are being used for microbiota measurements. We evaluated the stability of Scope mouthwash samples at ambient temperature and determined the comparability of Scope mouthwash with saliva collection using the OMNIgene ORAL kit. METHODS:Fifty-three healthy volunteers from Mayo Clinic and fifty cohort members from Bangladesh provided oral samples. One aliquot of the OMNIgene ORAL and Scope mouthwash were frozen immediately and one aliquot of the Scope mouthwash remained at ambient temperature for four days and then was frozen. DNA was extracted and the V4 region of the 16S rRNA gene was PCR amplified and sequenced using the HiSeq. Intraclass correlation coefficients (ICC) were calculated. RESULTS:The overall stability of the Scope mouthwash samples was relatively high for alpha and beta diversity. For example, the meta-analyzed ICC for the Shannon Index was 0.86 (95% CI: 0.76, 0.96). Similarly, the ICCs for the relative abundance of the top 25 genera were generally high. The comparability of the two sample types was relatively low when measured using ICCs, but were increased by using a Spearman correlation coefficient (SCC) to compare the rank order of individuals. CONCLUSIONS:Overall, the Scope mouthwash samples appear to be stable at ambient temperature which suggests that oral rinse samples received by the mail can be used for microbial analyses. However, Scope mouthwash samples were distinct compared to OMNIgene ORAL samples. IMPACT/CONCLUSIONS:Studies should try to compare oral microbial metrics within one sample collection type.

BACKGROUND & AIMS/OBJECTIVE:Previous studies reported an association of the bacteria Helicobacter pylori, the primary cause of gastric cancer, and risk of colorectal cancer (CRC). However, these findings have been inconsistent, appear to vary with population characteristics, and may be specific for virulence factor VacA. To more thoroughly evaluate the potential association of H pylori antibodies with CRC risk, we assembled a large consortium of cohorts representing diverse populations in the United States. METHODS:We used H pylori multiplex serologic assays to analyze serum samples from 4063 incident cases of CRC, collected before diagnosis, and 4063 matched individuals without CRC (controls) from 10 prospective cohorts for antibody responses to 13 H pylori proteins, including virulence factors VacA and CagA. The association of sero-positivity to H pylori proteins, as well as protein-specific antibody level, with odds of CRC was determined by conditional logistic regression. RESULTS:Overall 40% of controls and 41% of cases were H. pylori sero-positive (odds ratio [OR], 1.09; 95% CI, 0.99-1.20). H pylori VacA-specific sero-positivity was associated with an 11% increased odds of CRC (OR, 1.11; 95% CI, 1.01-1.22), and this association was particularly strong among African Americans (OR, 1.45; 95% CI, 1.08-1.95). Additionally, odds of CRC increased with level of VacA antibody in the overall cohort (P=.008) and specifically among African Americans (P=.007). CONCLUSION/CONCLUSIONS:In an analysis of a large consortium of cohorts representing diverse populations, we found serologic responses to H pylori VacA to associate with increased risk of CRC risk-particularly for African Americans. Future studies should seek to understand whether this marker is related to virulent H pylori strains carried in these populations.