The gut microbiome may play a role in inflammation associated with type 2 diabetes (T2D) development. This cross-sectional study examined its relation with glycemic status within a subset of the ...Multiethnic Cohort (MEC) and estimated the association of circulating bacterial endotoxin (measured as plasma lipopolysaccharide-binding protein (LBP)) with T2D, which may be mediated by C-reactive protein (CRP).
In 2013-16, cohort members from five ethnic groups completed clinic visits, questionnaires, and stool and blood collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose >125 and 100-125 mg/dL were classified as undiagnosed (UT2D) and pre-diabetes (PT2D) cases, respectively. We characterized the gut microbiome through 16S rRNA gene sequencing and measured plasma LBP and CRP by standard assays. Linear regression was applied to estimate associations of the gut microbiome community structure and LBP with T2D status adjusting for relevant confounders.
Among 1,702 participants (59.9-77.4 years), 735 (43%) were normoglycemic (NG), 506 (30%) PT2D, 154 (9%) UT2D, and 307 (18%) T2D. The Shannon diversity index decreased (ptrend = 0.05), while endotoxin, measured as LBP, increased (ptrend = 0.0003) from NG to T2D. Of 10 phyla, Actinobacteria (ptrend = 0.007), Firmicutes (ptrend = 0.003), and Synergistetes (ptrend = 0.02) were inversely associated and Lentisphaerae (ptrend = 0.01) was positively associated with T2D status. Clostridium sensu stricto 1, Lachnospira, and Peptostreptococcaceae were less, while Escherichia-Shigella and Lachnospiraceae were more abundant among T2D patients, but the associations with Actinobacteria, Clostridium sensu stricto 1, and Escherichia-Shigella may be due metformin use. PT2D/UT2D values were closer to NG than T2D. No indication was detected that CRP mediated the association of LBP with T2D.
T2D but not PT2D/UT2D status was associated with lower abundance of SCFA-producing genera and a higher abundance of gram-negative endotoxin-producing bacteria suggesting that the gut microbiome may contribute to chronic systemic inflammation and T2D through bacterial translocation.
The Healthy Eating Index-2015 (HEI-2015) was created to assess conformance of dietary intake with the Dietary Guidelines for Americans (DGA) 2015-2020. We assessed the association between the ...HEI-2015 and mortality from all-cause, cardiovascular disease (CVD), and cancer in the Multiethnic Cohort (MEC). White, African American, Native Hawaiian, Japanese American, and Latino adults (
> 215,000) from Hawaii and California completed a quantitative food-frequency questionnaire at study enrollment. HEI-2015 scores were divided into quintiles for men and women. Radar graphs were used to demonstrate how dietary components contributed to HEI-2015 scores. Mortality was documented over 17-22 years of follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox proportional hazards models. High HEI-2015 scores were inversely associated with risk of mortality from all-cause, CVD, and cancer for men and women (
-trend <0.0001 for all models). For men, the HRs (CIs) for all-cause, CVD, and cancer comparing the highest to the lowest quintile were 0.79 (0.76, 0.82), 0.76 (0.71, 0.82), and 0.80 (0.75, 0.87), respectively. For women, the HRs were 0.79 (0.76, 0.82), 0.75 (0.70, 0.81), and 0.84 (0.78, 0.91), respectively. These results, in a multiethnic population, demonstrate that following a diet aligned with the DGAs 2015-2020 recommendations is associated with lower risk of mortality from all-cause, CVD, and cancer.
Coffee consumption has been associated with reduced risk for death in prospective cohort studies; however, data in nonwhites are sparse.
To examine the association of coffee consumption with risk for ...total and cause-specific death.
The MEC (Multiethnic Cohort), a prospective population-based cohort study established between 1993 and 1996.
Hawaii and Los Angeles, California.
185 855 African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites aged 45 to 75 years at recruitment.
Outcomes were total and cause-specific mortality between 1993 and 2012. Coffee intake was assessed at baseline by means of a validated food-frequency questionnaire.
58 397 participants died during 3 195 484 person-years of follow-up (average follow-up, 16.2 years). Compared with drinking no coffee, coffee consumption was associated with lower total mortality after adjustment for smoking and other potential confounders (1 cup per day: hazard ratio HR, 0.88 95% CI, 0.85 to 0.91; 2 to 3 cups per day: HR, 0.82 CI, 0.79 to 0.86; ≥4 cups per day: HR, 0.82 CI, 0.78 to 0.87; P for trend < 0.001). Trends were similar between caffeinated and decaffeinated coffee. Significant inverse associations were observed in 4 ethnic groups; the association in Native Hawaiians did not reach statistical significance. Inverse associations were also seen in never-smokers, younger participants (<55 years), and those who had not previously reported a chronic disease. Among examined end points, inverse associations were observed for deaths due to heart disease, cancer, respiratory disease, stroke, diabetes, and kidney disease.
Unmeasured confounding and measurement error, although sensitivity analysis suggested that neither was likely to affect results.
Higher consumption of coffee was associated with lower risk for death in African Americans, Japanese Americans, Latinos, and whites.
National Cancer Institute.
We compared fat storage in the abdominal region among individuals from 5 different ethnic–racial groups to determine whether fat storage is associated with disparities observed in metabolic syndrome ...and other obesity-associated diseases.
We collected data from 1794 participants in the Multiethnic Cohort Study (60–77 years old; of African, European white, Japanese, Latino, or Native Hawaiian ancestry) with body mass index values of 17.1–46.2 kg/m2. From May 2013 through April 2016, participants visited the study clinic to undergo body measurements, an interview, and a blood collection. Participants were evaluated by dual-energy x-ray absorptiometry and abdominal magnetic resonance imaging. Among ethnic groups, we compared adiposity of the trunk, intra-abdominal visceral cavity, and liver, adjusting for total fat mass; we evaluated the association of adult weight change with abdominal adiposity; and we examined the prevalence of metabolic syndrome mediated by abdominal adiposity.
Relative amounts of trunk, visceral, and liver fat varied significantly with ethnicity—they were highest in Japanese Americans, lowest in African Americans, and intermediate in the other groups. Compared with African Americans, the mean visceral fat area was 45% and 73% greater in Japanese American men and women, respectively, and the mean measurements of liver fat were 61% and 122% greater in Japanese American men and women. The visceral and hepatic adiposity associated with weight gain since participants were 21 years old varied in a similar pattern among ethnic–racial groups. In the mediation analysis, visceral and liver fat jointly accounted for a statistically significant fraction of the difference in metabolic syndrome prevalence, compared with white persons, for African Americans, Japanese Americans, and Native Hawaiian women, independently of total fat mass.
In an analysis of data from the participants in the Multiethnic Cohort Study, we found extensive differences among ethnic–racial groups in the propensity to store fat intra-abdominally. This observation should be considered by clinicians in the prevention and early detection of metabolic disorders.
It has been recently hypothesized that many of the signals detected in genome-wide association studies (GWAS) to T2D and other diseases, despite being observed to common variants, might in fact ...result from causal mutations that are rare. One prediction of this hypothesis is that the allelic associations should be population-specific, as the causal mutations arose after the migrations that established different populations around the world. We selected 19 common variants found to be reproducibly associated to T2D risk in European populations and studied them in a large multiethnic case-control study (6,142 cases and 7,403 controls) among men and women from 5 racial/ethnic groups (European Americans, African Americans, Latinos, Japanese Americans, and Native Hawaiians). In analysis pooled across ethnic groups, the allelic associations were in the same direction as the original report for all 19 variants, and 14 of the 19 were significantly associated with risk. In summing the number of risk alleles for each individual, the per-allele associations were highly statistically significant (P<10(-4)) and similar in all populations (odds ratios 1.09-1.12) except in Japanese Americans the estimated effect per allele was larger than in the other populations (1.20; P(het) = 3.8×10(-4)). We did not observe ethnic differences in the distribution of risk that would explain the increased prevalence of type 2 diabetes in these groups as compared to European Americans. The consistency of allelic associations in diverse racial/ethnic groups is not predicted under the hypothesis of Goldstein regarding "synthetic associations" of rare mutations in T2D.
Summary
Background and Aims
Lifestyle factors are well associated with risk of hepatocellular carcinoma (HCC). However, the impact of reducing adverse lifestyle behaviours on population‐level burden ...of HCC is uncertain.
Methods
We conducted prospective analysis of the population‐based multi‐ethnic cohort (MEC) with linkage to cancer registries. The association of lifestyle factors (smoking, alcohol, diet quality assessed by alternate Mediterranean diet score, coffee drinking, physical activity and body mass index) with HCC incidence was examined using Cox regression. Population‐attributable risk (PAR, %) for the overall, lean and overweight/obese populations was determined.
Results
A total of 753 incident cases of HCC were identified in 181,346 participants over median follow‐up of 23.1 years. Lifestyle factors associated with elevated HCC risk included former/current smoking, heavy alcohol use, poor diet quality, lower coffee intake and obesity, but not physical activity. The lifestyle factor with highest PAR was lower coffee intake (21.3%; 95% CI: 8.9%–33.0%), followed by current smoking (15.1%; 11.1%–19.0%), obesity (14.5%; 9.2%–19.8%), heavy alcohol use (7.1%; 3.5%–10.6%) and lower diet quality (4.1%; 0.1%–8.1%). The combined PAR of all high‐risk lifestyle factors was 51.9% (95% CI: 30.1%–68.6%). A higher combined PAR was observed among lean (65.2%, 26.8%–85.7%) compared to overweight/obese (37.4%, 11.7%–58.3%) participants. Adjusting for viral hepatitis status in a linked MEC‐Medicare dataset resulted in similar PAR results.
Conclusions
Modifying lifestyle factors, particularly coffee intake, may have a substantial impact on HCC burden in diverse populations, with greater impact among lean adults. Diet and lifestyle counselling should be incorporated into HCC prevention strategies.
Individual and grouped population attributable risk of modificable lifestyle factors to incident hepatocellular carcinoma in a multi‐ethnic cohort.
National cancer incidence trends are presented for eight Asian American groups: Asian Indians/Pakistanis, Chinese, Filipinos, Japanese, Kampucheans, Koreans, Laotians, and Vietnamese.
Cancer ...incidence data from 1990 through 2008 were obtained from 13 Surveillance, Epidemiology, End Results (SEER) registries. Incidence rates from 1990 through 2008 and average percentage change were computed using SEER*Stat and Joinpoint software. The annual percentage change (APC) in incidence rates was estimated with 95% confidence intervals (95% CIs) calculated for both the rate and APC estimates. Rates for non-Hispanic whites are presented for comparison.
Prostate cancer was the most common malignancy among most groups, followed by lung, colorectal, liver, and stomach cancers. Breast cancer was generally the most common cancer in women, followed by colorectal and lung cancers; liver, cervix, thyroid, and stomach cancers also ranked highly. Among men, increasing trends were observed for prostate (Asian Indians and Pakistanis: APC 1990-2003 = 2.2, 95% CI = 0.3 to 4.1; Filipinos: APC 1990-1994 = 19.0, 95% CI = 4.5 to 35.4; Koreans: APC 1990-2008 = 2.9, 95% CI = 1.8 to 4.0), colorectal (Koreans: APC 1990-2008 = 2.2, 95% CI = 0.9 to 3.5), and liver cancers (Filipinos: APC 1990-2008 = 1.6, 95% CI = 0.4 to 2.7; Koreans: APC 1990-2006 = 2.1, 95% CI = 0.4 to 3.7; Vietnamese: APC 1990-2008 = 1.6, 95% CI = 0.3 to 2.8), whereas lung and stomach cancers generally remained stable or decreased. Among women, increases were observed for uterine cancer (Asian Indians: APC 1990-2008 = 3.0, 95% CI = 0.3 to 5.8; Chinese: APC 2004-2008 = 7.0, 95% CI = 1.4 to 12.9; Filipina: APC 1990-2008 = 3.0, 95% CI = 2.4 to 3.7; Japanese: APC 1990-2008 = 1.1, 95% CI = 0.1 to 2.0), colorectal cancer (Koreans: APC 1990-2008 = 2.8, 95% CI = 1.7 to 3.9; Laotians: APC: 1990-2008 = 5.9, 95% CI = 4.0 to 7.7), lung cancer (Filipinas: APC 1990-2008 = 2.1, 95% CI = 1.4 to 2.8; Koreans: APC 1990-2008 = 2.1, 95% CI = 0.6 to 3.6), thyroid cancer (Filipinas: APC 1990-2008 = 2.5, 95% CI = 1.7 to 3.3), and breast cancer in most groups (APC 1990-2008 from 1.2 among Vietnamese and Chinese to 4.7 among Koreans). Decreases were observed for stomach (Chinese and Japanese), colorectal (Chinese), and cervical cancers (Laotians and Vietnamese).
These data fill a critical knowledge gap concerning the cancer experience of Asian American groups and highlight where increased preventive, screening, and surveillance efforts are needed-in particular, lung cancer among Filipina and Korean women and Asian Indian/Pakistani men, breast cancer among all women, and liver cancer among Vietnamese, Laotian, and Kampuchean women and Filipino, Kampuchean, and Vietnamese men.
Abstract
The purpose of this study was to examine whether the increased risk of colorectal cancer due to cigarette smoking differed by anatomical subsite or sex. We analyzed data from 188,052 ...participants aged 45–75 years (45% men) who were enrolled in the Multiethnic Cohort Study in 1993–1996. During a mean follow-up period of 16.7 years, we identified 4,879 incident cases of invasive colorectal adenocarcinoma. In multivariate Cox regression models, as compared with never smokers of the same sex, male ever smokers had a 39% higher risk (hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.16, 1.67) of cancer of the left (distal or descending) colon but not of the right (proximal or ascending) colon (HR = 1.03, 95% CI: 0.89, 1.18), while female ever smokers had a 20% higher risk (HR = 1.20, 95% CI: 1.06, 1.36) of cancer of the right colon but not of the left colon (HR = 0.96, 95% CI: 0.80, 1.15). Compared with male smokers, female smokers had a greater increase in risk of rectal cancer with number of pack-years of smoking (P for heterogeneity = 0.03). Our results suggest that male smokers are at increased risk of left colon cancer and female smokers are at increased risk of right colon cancer. Our study also suggests that females who smoke may have a higher risk of rectal cancer due to smoking than their male counterparts.
Trimethylamine N-oxide (TMAO), a compound derived from diet and metabolism by the gut microbiome, has been associated with several chronic diseases, although the mechanisms of action are not well ...understood and few human studies have investigated microbes involved in its production.
Our study aims were 1) to investigate associations of TMAO and its precursors (choline, carnitine, and betaine) with inflammatory and cardiometabolic risk biomarkers; and 2) to identify fecal microbiome profiles associated with TMAO.
We conducted a cross-sectional analysis using data collected from 1653 participants (826 men and 827 women, aged 60–77 y) in the Multiethnic Cohort Study. Plasma concentrations of TMAO and its precursors were measured by LC-tandem MS. We also analyzed fasting blood for markers of inflammation, glucose and insulin, cholesterol, and triglycerides (TGs), and further measured blood pressure. Fecal microbiome composition was evaluated by sequencing the 16S ribosomal RNA gene V1–V3 region. Associations of TMAO and its precursors with disease risk biomarkers were assessed by multivariable linear regression, whereas associations between TMAO and the fecal microbiome were assessed by permutational multivariate ANOVA and hurdle regression models using the negative binomial distribution.
Median (IQR) concentration of plasma TMAO was 3.05 μmol/L (2.10–4.60 μmol/L). Higher concentrations of TMAO and carnitine, and lower concentrations of betaine, were associated with greater insulin resistance (all P < 0.02). Choline was associated with higher systolic blood pressure, TGs, lipopolysaccharide-binding protein, and lower HDL cholesterol (P ranging from <0.001 to 0.03), reflecting an adverse cardiometabolic risk profile. TMAO was associated with abundance of 13 genera (false discovery rate < 0.05), including Prevotella, Mitsuokella, Fusobacterium, Desulfovibrio, and bacteria belonging to the families Ruminococcaceae and Lachnospiraceae, as well as the methanogen Methanobrevibacter smithii.
Plasma TMAO concentrations were associated with a number of trimethylamine-producing bacterial taxa, and, along with its precursors, may contribute to inflammatory and cardiometabolic risk pathways.
There is a growing body of evidence supporting the protective effect of statins on the risk of prostate cancer, in particular aggressive disease. Past research has mostly been conducted in North ...American cohorts of White men.
In the multiethnic cohort (MEC), we investigated the association of prediagnostic statin use with the incidence and mortality of prostate cancer across five racial/ethnic groups (White, African American, Japanese American, Latino, and Native Hawaiian).
Among 31,062 male participants who completed a detailed medication questionnaire, 31.4% reported use of statins, 2,748 developed prostate cancer, and 261 died from the disease. After adjusting for potential confounders, prediagnostic statin use was associated with a 32% lower risk of fatal prostate cancer 95% confidence interval (CI) = 0.50-0.91, with the inverse association suggested consistently across the five racial/ethnic groups. Moreover, an 11% lower risk of aggressive prostate cancer (95% CI = 0.76-1.03) was observed in statin users than in nonusers. We found no statistically significant association between prediagnostic statin use and total prostate cancer or nonaggressive disease. Prediagnostic statin use was suggestively associated with a 19% reduction in prostate cancer-specific mortality (95% CI = 0.59-1.10) and an 8% reduction in all-cause mortality (95% CI = 0.79-1.07).
In the MEC, prediagnostic use of statin was associated with lower risks of aggressive forms of prostate cancer.
Our findings provide further support for the potential benefits of statins in reducing the risk and mortality of prostate cancer, especially aggressive disease.
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