Publications by authors named "Kristine R Monroe"

95 Publications

Associations of the gut microbiome with hepatic adiposity in the Multiethnic Cohort Adiposity Phenotype Study.

Gut Microbes 2021 Jan-Dec;13(1):1965463

Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, U.S.A.

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for liver cancer and prevalence varies by ethnicity. Along with genetic and lifestyle factors, the gut microbiome (GM) may contribute to NAFLD and its progression to advanced liver disease. Our cross-sectional analysis assessed the association of the GM with hepatic adiposity among African American, Japanese American, White, Latino, and Native Hawaiian participants in the Multiethnic Cohort. We used MRI to measure liver fat and determine nonalcoholic fatty liver disease (NAFLD) status (n = 511 cases) in 1,544 participants, aged 60-77 years, with 12-53% overall adiposity (BMI of 17.8-46.2 kg/m). The GM was measured by 16S rRNA gene sequencing and, on a subset, by metagenomic sequencing. Alpha diversity was lower overall with NAFLD and in certain ethnicities (African Americans, Whites, and Latinos). In models regressing genus on NAFLD status, 62 of 149 genera (40%) exhibited a significant interaction between NAFLD and ethnicity stratified analysis found 69 genera significantly associated with NAFLD in at least one ethnic group. No single genus was significantly associated with NAFLD across all ethnicities. In contrast, the same bacterial metabolic pathways were over-represented in participants with NAFLD regardless of ethnicity. Imputed secondary bile acid and carbohydrate pathways were associated with NAFLD, the latter of which was corroborated by metagenomics, although different genera in different ethnicities were associated with these pathways. Overall, we found that NAFLD was associated with altered bacterial composition and metabolism, and that bacterial endotoxin, assessed by plasma lipopolysaccharide binding protein (LBP), may mediate liver fat-associated systemic inflammation in a manner that seems to vary by ethnicity.
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http://dx.doi.org/10.1080/19490976.2021.1965463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425768PMC
September 2021

The Gut Microbiome Is Associated with Circulating Dietary Biomarkers of Fruit and Vegetable Intake in a Multiethnic Cohort.

J Acad Nutr Diet 2021 Jul 2. Epub 2021 Jul 2.

Background: Results from observational studies suggest high diet quality favorably influences the human gut microbiome. Fruit and vegetable consumption is often a key contributor to high diet quality.

Objective: To evaluate measures of gut bacterial diversity and abundance in relation to serum biomarkers of fruit and vegetable intake.

Design: Secondary analysis of cross-sectional data.

Participants And Setting: Men and women from Los Angeles, CA, and Hawai'i who participated in the Multiethnic Cohort-Adiposity Phenotype Study from 2013 to 2016 (N = 1,709).

Main Outcome Measures: Gut microbiome diversity and composition in relation to dietary biomarkers.

Statistical Analysis: Carotenoid (beta carotene, alpha carotene, cryptoxanthins, lutein, lycopene, and zeaxanthin), tocopherol (α, β + γ, and δ), and retinol concentrations were assessed in serum. The α and β diversity and composition of the gut microbiome were classified based on 16S rRNA gene sequencing of bacterial DNA from self-collected fecal samples. Global differences in microbial community profiles in relation dietary biomarkers were evaluated using multivariable permutational analysis of variance. Associations of α diversity (Shannon index), β diversity (weighted and unweighted UniFrac) with center log-ratio-transformed phyla and genera abundances were evaluated using linear regression, adjusted for covariates.

Results: Increasing total carotenoid, beta carotene, alpha carotene, cryptoxanthin, and lycopene concentrations were associated with higher gut bacterial diversity (Shannon Index) (P < 0.001). Total tocopherol, α-tocopherol, and δ-tocopherol concentrations contributed significantly to more than 1% of the microbiome variation in gut bacterial community: total tocopherol: 1.74%; α-tocopherol: 1.70%; and δ-tocopherol: 1.16% (P < 0.001). Higher total carotenoid was associated with greater abundance of some genera relevant for microbial macronutrient metabolism (P < 0.001).

Conclusions: Objective biomarkers of fruit and vegetable intake, particularly carotenoids, were favorably associated with gut bacterial composition and diversity in this multiethnic population. These observations provide supportive evidence that fruit and vegetable intake is related to gut bacterial composition; more work is needed to elucidate how this influences host health.
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http://dx.doi.org/10.1016/j.jand.2021.05.023DOI Listing
July 2021

Metabolic syndrome screening using visceral adipose tissue (VAT) from opportunistic MRI locations in a multi-ethnic population.

Obes Res Clin Pract 2021 May-Jun;15(3):227-234. Epub 2021 May 21.

University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA. Electronic address:

Objective: To determine if visceral adipose tissue (VAT) area measured through MRI can be used opportunistically to assess the presence of cardiometabolic risk factors and compare its performance to simpler adiposity measures.

Methods: A cross-sectional analysis was carried out on a subset of 1683 participants (856 women) from the Adiposity Phenotype Study (mean age=69.2y; range 59.9-77.4). The association of total VAT area (sum of four cross sections, L1-L2, L2-L3, L3-L4, L4-L5) and each location, as well as BMI and body fat % (per SD) with the metabolic syndrome (MetSx) or its components was evaluated through logistic regression analysis.

Results: Total VAT can be accurately predicted using all sites evaluated (R range=0.82-0.96). In men, VAT did not show a superior association to MetSx compared to BMI in men. However, in women, VAT was consistently superior to BMI and body fat % in its association to MetSx, independent of ethnicity [odds ratio for BMI, body fat %and total VAT area=2.25 (95% CI: 1.93-2.62); 1.66 (95% CI: 1.36-2.03); 6.20 (95% CI: 4.69-8.21) respectively in all women]. Ethnic-specific odds ratios to MetSx in women ranged from 5.38 to 8.63 for total VAT area and 2.12-4.08 for BMI.

Conclusion: Total VAT area can be accurately predicted from individual VAT regions in men and women and offers superior association to BMI for MetSx in women but not in men for five ethnicities. Therefore, opportunistic screening for elevated VAT area in women may be warranted across multiple ethnic groups.
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http://dx.doi.org/10.1016/j.orcp.2021.03.007DOI Listing
September 2021

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies.

Am J Clin Nutr 2021 08;114(2):450-461

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.

Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes.

Objective: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status.

Method: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models.

Results: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d).

Conclusion: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.
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http://dx.doi.org/10.1093/ajcn/nqab097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326053PMC
August 2021

Body Fat Distribution, Glucose Metabolism, and Diabetes Status among Older Adults: The Multiethnic Cohort Adiposity Phenotype Study.

J Epidemiol 2021 Feb 27. Epub 2021 Feb 27.

University of Hawaii Cancer Center.

Aims: As the proportion of visceral (VAT) to subcutaneous adipose tissue (SAT) may contribute to type 2 diabetes (T2D) development, we examined this relation in a cross-sectional design within the Multiethnic Cohort that includes Japanese Americans known to have high VAT. The aim was to understand how ectopic fat accumulation differs by glycemic status across ethnic groups with disparate rates of obesity, T2D, and propensity to accumulate VAT.

Methods: In 2013-16, 1,746 participants aged 69.2 (2.7) years from five ethnic groups completed questionnaires, blood collections, and whole-body DXA and abdominal MRI scans. Participants with self-reported T2D and/or medication were classified as T2D, those with fasting glucose >125 and 100-125 mg/dL as undiagnosed cases (UT2D) and prediabetes (PT2D), respectively. Using linear regression, we estimated adjusted means of adiposity measures by T2D status.

Results: Overall, 315 (18%) participants were classified as T2D, 158 (9%) as UT2D, 518 (30%) as PT2D, and 755 (43%) as normoglycemic (NG) with significant ethnic differences (p<0.0001). In fully adjusted models, VAT, VAT/SAT, and percent liver fat increased significantly from NG, PT2D, UT2D, to T2D (p<0.001). Across ethnic groups, the VAT/SAT ratio was lowest for NG participants and highest for T2D cases. Positive trends were observed in all groups except African Americans, with highest VAT/SAT in Japanese Americans.

Conclusions: These findings indicate that VAT plays an important role in T2D etiology, in particular among Japanese Americans with high levels of ectopic adipose tissue, which drives the development of T2D to a greater degree than in other ethnic groups.
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http://dx.doi.org/10.2188/jea.JE20200538DOI Listing
February 2021

Diabetes-Related Complications and Pancreatic Cancer Incidence in the Multiethnic Cohort.

JNCI Cancer Spectr 2020 Oct 4;4(5):pkaa035. Epub 2020 May 4.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Background: People with diabetes are at an increased risk of developing pancreatic cancer. However, it is unclear whether diabetes-related complications are associated with risk of pancreatic cancer.

Methods: A nested matched case-control analysis was conducted among the fee-for-service Medicare participants of the prospective Multiethnic Cohort (n = ∼123 000). Between 2001 and 2014, 433 incident cases of pancreatic ductal adenocarcinoma were matched to 1728 controls by birth year, sex, race and ethnicity, and age at cohort entry. Participants were linked to data from the California and Hawaii cancer registries and Medicare claims. We used the diabetes complications severity index (DCSI) for the presence of 7 complications within 2 years prior to the diagnosis date of the index case. Multivariable conditional logistic regression was used to examine the association of DCSI with pancreatic cancer incidence.

Results: Diabetes was present among 45.4% of cases and 34.1% of controls. Cases had higher DCSI score compared with controls (score ≥4: 32.8% in cases; 21.2% in controls). The most prevalent diabetes-related complications for cases were cardiovascular disease (61.2%), nephropathy (31.2%), and cerebrovascular disease (21.7%). Individuals with diabetes (odds ratio [OR] = 1.48, 95% confidence interval [CI] = 1.14 to 1.91), nephropathy (OR = 1.75, 95% CI = 1.32 to 2.33), cardiovascular disease (OR = 1.88, 95% CI = 1.45 to 2.44), and metabolic complications (OR = 6.61, 95% CI = 2.49 to 17.50) were at increased risk of pancreatic cancer. For every 1-unit increase in DCSI score, participants had 18% greater risk of pancreatic cancer (OR = 1.18, 95% CI = 1.11 to 1.25).

Conclusions: Participants with diabetes-related complications have an elevated risk of pancreatic cancer. Identifying diabetes-related complications may help identify high-risk groups who can be studied for development of early markers for this fatal cancer.
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http://dx.doi.org/10.1093/jncics/pkaa035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583154PMC
October 2020

Genome-Wide Association Study of Liver Fat: The Multiethnic Cohort Adiposity Phenotype Study.

Hepatol Commun 2020 Aug 25;4(8):1112-1123. Epub 2020 Jun 25.

Department of Epidemiology and Biostatistics University of California, San Francisco San Francisco CA USA.

The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population-specific genetic variants associated with liver fat. We conducted a genome-wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population-based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin-like phospholipase domain containing 3 () at 22q13 was confirmed to be associated with percent liver fat ( = 3.52 × 10) but more strongly in women than men ( heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.028;  = 0.009) and circulating levels of insulin (beta = 0.022;  = 0.020) and alanine aminotransferase (beta = 0.016;  = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [] and collagen type XIX alpha 1 chain [] ( = 1.42 × 10) was also observed. Rs7724941 was associated with HOMA-IR (beta = 0.12;  = 0.0005), insulin (beta = 0.11;  = 0.0003), triglycerides (beta = 0.059;  = 0.01), high-density lipoprotein (beta = -0.046;  = 0.04), and sex hormone binding globulin (beta = -0.084;  = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). : We replicated the rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association.
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http://dx.doi.org/10.1002/hep4.1533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395069PMC
August 2020

Hospital Characteristics and Breast Cancer Survival in the California Breast Cancer Survivorship Consortium.

JCO Oncol Pract 2020 06;16(6):e517-e528

Stanford Cancer Institute, Stanford, CA.

Introduction: Racial/ethnic disparities in breast cancer survival are well documented, but the influence of health care institutions is unclear. We therefore examined the effect of hospital characteristics on survival.

Methods: Harmonized data pooled from 5 case-control and prospective cohort studies within the California Breast Cancer Survivorship Consortium were linked to the California Cancer Registry and the California Neighborhoods Data System. The study included 9,701 patients with breast cancer who were diagnosed between 1993 and 2007. First reporting hospitals were classified by hospital type-National Cancer Institute (NCI) -designated cancer center, American College of Surgeons (ACS) Cancer Program, other-and hospital composition of the neighborhood socioeconomic status and race/ethnicity of patients with cancer. Multivariable Cox proportional hazards models adjusted for clinical and patient-level prognostic factors were used to examine the influence of hospital characteristics on survival.

Results: Fewer than one half of women received their initial care at an NCI-designated cancer center (5%) or ACS program (38%) hospital. Receipt of initial care in ACS program hospitals varied by race/ethnicity-highest among non-Latina White patients (45%), and lowest among African Americans (21%). African-American women had superior breast cancer survival when receiving initial care in ACS hospitals versus other hospitals (non-ACS program and non-NCI-designated cancer center; hazard ratio, 0.67; 95% CI, 0.55 to 0.83). Other hospital characteristics were not associated with survival.

Conclusion: African American women may benefit significantly from breast cancer care in ACS program hospitals; however, most did not receive initial care at such facilities. Future research should identify the aspects of ACS program hospitals that are associated with higher survival and evaluate strategies by which to enhance access to and use of high-quality hospitals, particularly among African American women.
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http://dx.doi.org/10.1200/OP.20.00064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462568PMC
June 2020

The joint association of cardiometabolic health and weight on mortality in the multiethnic cohort.

Ethn Health 2020 Jun 7:1-14. Epub 2020 Jun 7.

Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawaii Cancer Center, Manoa, HI, USA.

While cardiometabolic abnormalities are associated with elevated risk of morbidity, they may not occur in all individuals with obesity. Less is known about associations with mortality, especially cancer mortality. This study examined associations between cardiometabolic-weight categories and mortality from cardiovascular disease (CVD), cancer, and all causes. Cox proportional hazards regressions of time to all-cause, CVD, and cancer mortalities were used to examine associations with cardiometabolic-weight status, in the Multiethnic Cohort (=157,865). Cardiometabolic-weight status categories were: Metabolically Healthy Normal Weight, Metabolically Healthy Obese, Metabolically Healthy Overweight, Metabolically Unhealthy Normal Weight, Metabolically Unhealthy Obese, and Metabolically Unhealthy Overweight. Higher mortality, especially for all-cause and CVD, was found for all metabolically unhealthy groups no matter the weight classification when compared to the Metabolically Healthy Normal Weight category across sex-ethnic groups. For all-cause mortality, a reduction in mortality was seen for males in the Metabolically Healthy Overweight category (HR: 0.88, 95% CI: 0.84, 0.93), especially for African American, Native Hawaiian, and Latino males. Mortality was elevated in the Metabolically Healthy Obese category for all-cause and CVD mortality in both sexes (HR: 1.08-1.93). Few associations were seen with cancer mortality. Past examinations of cardiometabolic-weight status and mortality have been hampered by a lack of diversity. In a racially/ethnically diverse population, metabolically unhealthy groups exhibited a substantially higher risk of death from all causes and CVD than metabolically healthy groups. A reduction in all-cause mortality was seen for some males classified as Metabolically Healthy Overweight; however, being classified as Metabolically Healthy Obese elevated mortality risk for males and females compared to Metabolically Healthy Normal Weight. Future research is needed to examine how sex-ethnic differences in body fat distribution and changes in weight over time influence associations between cardiometabolic-weight status and mortality.
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http://dx.doi.org/10.1080/13557858.2020.1771680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719582PMC
June 2020

Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project.

J Hepatol 2020 10 11;73(4):863-872. Epub 2020 May 11.

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.

Background & Aims: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear.

Methods: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study.

Results: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only.

Conclusion: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography.

Lay Summary: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.
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http://dx.doi.org/10.1016/j.jhep.2020.04.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901003PMC
October 2020

Diet Quality and Breast Cancer Incidence in the Multiethnic Cohort.

Eur J Clin Nutr 2020 12 14;74(12):1743-1747. Epub 2020 Apr 14.

University of Hawaii Cancer Center, Honolulu, HI, USA.

This study investigated the relation of diet quality indexes (DQI) with breast cancer incidence among women from the Multiethnic Cohort (MEC). Participants completed a questionnaire with a validated food frequency questionnaire. Scores for Healthy Eating Index 2015 (HEI-2015), Alternate Healthy Eating Index 2010 (AHEI-2010), alternate Mediterranean diet score (aMED), and Dietary Approaches to Stop Hypertension (DASH) were divided into quintiles (Q1-Q5). Cox regression was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for DQIs and breast cancer risk adjusted for known risk factors. The respective HRs for Q5 vs. Q1 were: 1.06 (95% CI, 0.98-1.14) for HEI-2015, 0.96 (95% CI, 0.90-1.04) for AHEI-2010, 1.01 (95% CI, 0.94-1.09) for aMED, and 0.95 (95% CI, 0.88-1.02) for DASH (p > 0.05 for all). However, overweight and obesity were significantly associated with breast cancer incidence. Despite the null association for DQIs, diet quality may lower breast cancer risk through its positive influence on weight status.
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http://dx.doi.org/10.1038/s41430-020-0627-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554070PMC
December 2020

Circulating Biomarker Score for Visceral Fat and Risks of Incident Colorectal and Postmenopausal Breast Cancer: The Multiethnic Cohort Adiposity Phenotype Study.

Cancer Epidemiol Biomarkers Prev 2020 05 4;29(5):966-973. Epub 2020 Mar 4.

University of Hawaii Cancer Center, Honolulu, Hawaii.

Background: Visceral adipose tissue (VAT) may play a greater role than subcutaneous fat in increasing cancer risk but is poorly estimated in epidemiologic studies.

Methods: We developed a VAT prediction score by regression equations averaged across 100 least absolute shrinkage and selection operator models in a cross-sectional study of 1,801 older adults in the Multiethnic Cohort (MEC). The score was then used as proxy for VAT in case-control studies of postmenopausal breast (950 case-control pairs) and colorectal (831 case-control pairs) cancer in an independent sample in MEC. Abdominal MRI-derived VAT; circulating biomarkers of metabolic, hormonal, and inflammation dysfunctions; and ORs for incident cancer adjusted for BMI and other risk factors were assessed.

Results: The final score, composed of nine biomarkers, BMI, and height, explained 11% and 15% more of the variance in VAT than BMI alone in men and women, respectively. The area under the receiver operator curve for VAT >150 cm was 0.90 in men and 0.86 in women. The VAT score was associated with risk of breast cancer [OR (95% confidence interval [CI]) by increasing tertiles: 1.00, 1.09 (0.86-1.39), 1.48 (1.16-1.89); = 0.002] but not with colorectal cancer ( = 0.84), although an association [1.00, 0.98 (0.68-1.39), 1.24 (0.88-1.76); = 0.08] was suggested for this cancer after excluding cases that occurred within 7 years of blood draw ( = 0.06).

Conclusions: The VAT score predicted risks of postmenopausal breast cancer and can be used for risk assessment in diverse populations.

Impact: These findings provide specific evidence for a role of VAT in breast cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196505PMC
May 2020

Associations of plasma trimethylamine N-oxide, choline, carnitine, and betaine with inflammatory and cardiometabolic risk biomarkers and the fecal microbiome in the Multiethnic Cohort Adiposity Phenotype Study.

Am J Clin Nutr 2020 06;111(6):1226-1234

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1093/ajcn/nqaa015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266689PMC
June 2020

Differences in the association of diet quality with body fat distribution between men and women.

Eur J Clin Nutr 2020 10 24;74(10):1434-1441. Epub 2020 Jan 24.

University of Hawaii Cancer Center, Honolulu, HI, USA.

Background/objective: As dietary intake and endocrine metabolism are vastly different by sex, we evaluated differences in the association of diet quality with body composition between men and women.

Subjects/methods: Close to 2000 participants from the Multiethnic Cohort completed calibrated quantitative food frequency questionnaires at cohort entry (1993-96) and clinic visit (2013-16), from which the Healthy Eating Index (HEI-2010) was computed. Adiposity measures were obtained through DXA and MRI at clinic visit. Multivariable-adjusted mean adiposity measures were estimated by tertiles of HEI-2010 scores using general linear regression. The associations of diet quality with high visceral fat (VAT) and nonalcoholic fatty liver disease (NAFLD) were examined by logistic regression. To assess sex differences, cross-product terms with the HEI-2010 were added to the models.

Results: Mean HEI-2010 scores were higher for women than men at cohort entry (67.4 vs. 64.0) and clinic visit (73.6 vs. 71.0). Past and current diet quality was inversely associated with adiposity measures in men and women. Although interaction terms were not significant, the magnitude of the slopes and differences in adjusted means across tertiles suggested a stronger association for women than men. When comparing individuals who maintained a high vs. poor quality diet over 20 years, women but not men showed significantly lower risks for high VAT, whereas high HEI-2010 scores predicted a lower risk of NAFLD in both sexes.

Conclusions: The inverse association of diet quality with adiposity was similar in both sexes, but diet quality appeared to have a stronger influence on VAT in women than men.
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http://dx.doi.org/10.1038/s41430-020-0563-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377951PMC
October 2020

Association of change in the neighborhood obesogenic environment with colorectal cancer risk: The Multiethnic Cohort Study.

SSM Popul Health 2020 Apr 24;10:100532. Epub 2019 Dec 24.

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.

Background: Neighborhood environment has been associated with health behaviors. Despite the evidence of the influence of neighborhood social and physical factors on cancer risk, no research has evaluated whether changes in the neighborhood obesogenic environment, either by physical moves to different neighborhoods or experiencing neighborhood redevelopment or neglect, affect cancer risk.

Methods: The association of change in neighborhood environment attributes (socioeconomic status, population density, restaurant and retail food environments, numbers of recreational facilities and businesses, commute patterns, traffic density, and street connectivity) with colorectal cancer (CRC) risk was examined among 95,472 Los Angeles, CA, Multiethnic Cohort participants, including 2295 invasive CRC cases diagnosed between 1993 and 2010 using Cox proportional hazards regression, adjusting for age, race/ethnicity, other risk factors including BMI and physical activity, and baseline levels of neighborhood attributes. Stratified analyses were conducted by racial/ethnic group and moving status.

Results: 40% of participants moved (changed physical residence) during follow-up. Across all races/ethnicities, upward change in population density was statistically significantly associated with higher CRC risk among male and female non-movers (HR: 1.35 and 1.41, respectively). The same association was also observed separately among female African American and Japanese American non-movers, male Latino non-movers, female African American and male White movers. Downward change in population density was significantly related to higher CRC risk among female non-movers (HR: 1.33). Downward change in traffic density was associated with lower CRC risk among male non-movers but with higher CRC risk among female movers (HR: 0.66 and 1.43, respectively). Downward changes in street connectivity or the number of recreational facilities were associated with higher CRC risk (HR: 1.34 and 1.54, respectively). Upward change in the number of recreational facilities was associated with lower CRC risk among female non-movers (HR: 0.70). Changes in the other neighborhood attributes did not exhibit significant associations with CRC risk within more than one racial/ethnic group.

Conclusion: Changes over time in neighborhood attributes have an effect on the risk of colorectal cancer, which is separate from the baseline levels of the same attributes and individual-level risk factors, and differs between sexes, movers and non-movers and across racial/ethnic groups.
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http://dx.doi.org/10.1016/j.ssmph.2019.100532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940713PMC
April 2020

A phenome-wide association study (PheWAS) in the Population Architecture using Genomics and Epidemiology (PAGE) study reveals potential pleiotropy in African Americans.

PLoS One 2019 31;14(12):e0226771. Epub 2019 Dec 31.

Cleveland Institute for Computational Biology, Cleveland, Ohio, United States of America.

We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, between thousands of genetic variants assayed on the Metabochip and hundreds of phenotypes in 5,897 African Americans as part of the Population Architecture using Genomics and Epidemiology (PAGE) I study. The PAGE I study was a National Human Genome Research Institute-funded collaboration of four study sites accessing diverse epidemiologic studies genotyped on the Metabochip, a custom genotyping chip that has dense coverage of regions in the genome previously associated with cardio-metabolic traits and outcomes in mostly European-descent populations. Here we focus on identifying novel phenome-genome relationships, where SNPs are associated with more than one phenotype. To do this, we performed a PheWAS, testing each SNP on the Metabochip for an association with up to 273 phenotypes in the participating PAGE I study sites. We identified 133 putative pleiotropic variants, defined as SNPs associated at an empirically derived p-value threshold of p<0.01 in two or more PAGE study sites for two or more phenotype classes. We further annotated these PheWAS-identified variants using publicly available functional data and local genetic ancestry. Amongst our novel findings is SPARC rs4958487, associated with increased glucose levels and hypertension. SPARC has been implicated in the pathogenesis of diabetes and is also known to have a potential role in fibrosis, a common consequence of multiple conditions including hypertension. The SPARC example and others highlight the potential that PheWAS approaches have in improving our understanding of complex disease architecture by identifying novel relationships between genetic variants and an array of common human phenotypes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226771PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938343PMC
April 2020

Association of Imaging-Based Body Fat Distribution and Mammographic Density in the Multiethnic Cohort Adiposity Phenotype Study.

Cancer Epidemiol Biomarkers Prev 2020 02 14;29(2):352-358. Epub 2019 Nov 14.

University of Hawaii Cancer Center, Honolulu, Hawaii.

Background: As the stronger association of obesity with postmenopausal breast cancer in Asian than white women may be due to body fat distribution, we examined the relation of adiposity measures with percent mammographic density (PMD), a strong predictor of breast cancer incidence.

Methods: A total of 938 women from five ethnic groups (69.1 ± 2.7 years) in the Adiposity Phenotype Study (APS) underwent DXA and MRI imaging. PMD was assessed in routine mammograms using a computer-assisted method. Spearman correlation coefficients were computed and general linear models were applied to estimate regression coefficients (β) for PMD per 0.5 SD units of adiposity measures while adjusting for known confounders, including DXA total body fat.

Results: For 701 (75%) of the participants (69.1 ± 2.7 years), valid mammograms were obtained. Whereas total body fat, the trunk-to-periphery fat ratio (TPFR), visceral fat (VAT), and subcutaneous fat (SAT) were inversely correlated with PMD ( < 0.0001), the VAT/SAT ratio correlated positively ( = 0.10; = 0.01). In fully adjusted models, PMD remained inversely related to TPFR and SAT and disappeared for VAT, while it was strengthened for VAT/SAT (β = 0.51; = 0.009). This relation was stronger in Japanese Americans than other ethnic groups.

Conclusions: This is the first study to show an association of a high VAT/SAT ratio with greater PMD, a marker of breast cancer risk after taking into account total body fat.

Impact: The results indicate a link between the propensity to accumulate VAT and the amount of fat in the breast (1-PMD), which may influence the relation of obesity with breast cancer incidence.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007361PMC
February 2020

Diet Quality and Biomarker Profiles Related to Chronic Disease Prevention: The Multiethnic Cohort Study.

J Am Coll Nutr 2020 Mar-Apr;39(3):216-223. Epub 2019 Jul 10.

Population Sciences in the Pacific, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.

To understand how diet quality affects chronic disease etiology, the associations of 4 diet quality indices with blood levels of lipid-soluble micronutrients and biomarkers of inflammation, lipid, and glucose metabolism were examined in 5 ethnic groups. In a cross-sectional design, the Adiposity Phenotype Study, a subset of the Multiethnic Cohort in Hawaii and Los Angeles, recruited participants of white, African American, Native Hawaiian, Japanese American, and Latino ancestry. A total of 896 men and 910 women completed a validated quantitative food frequency questionnaire and anthropometric measurements and donated a fasting blood sample. Using general linear models, covariate-adjusted mean levels of lipid-soluble micronutrients (total carotenes, lycopene, total tocopherols, total lutein, cryptoxanthins), biomarkers of inflammation (C-reactive protein [CRP], tumor necrosis factor-[Formula: see text]), adipokines (adiponectin, leptin), lipids (total cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides), and glucose metabolism (glucose, insulin, homeostatic model assessment of insulin resistance [HOMA-IR]) were computed across tertiles of 4 dietary indices Healthy Eating Index (HEI)-2010, Alternative HEI (AHEI)-2010, alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH); trends were evaluated in models with diet quality scores as continuous variables. With better diet quality, levels of carotenes, lutein, cryptoxanthin, adiponectin, and HDL-C were significantly higher ( < 0.01), whereas levels of CRP, leptin, total cholesterol, triglycerides, glucose, insulin, and HOMA-IR were inversely associated ( < 0.05) with diet quality. With the exception of cryptoxanthins and triglycerides, the associations were consistent across ethnic groups. These findings confirm the association between diet quality and nutrition-related biomarkers and support the idea that a high-quality diet positively influences biologic pathways involved in chronic disease etiology across different ethnic groups.
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http://dx.doi.org/10.1080/07315724.2019.1635921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952587PMC
June 2021

Association of serum γ-tocopherol levels with mortality: the Multiethnic Cohort Study.

Eur J Clin Nutr 2020 01 26;74(1):87-96. Epub 2019 Jun 26.

Office of Public Health Studies, University of Hawaii at Manoa, Honolulu, HI, USA.

Background/objectives: γ-Tocopherol has unique properties that protect against nitrogen oxide-mediated cellular damage. To elucidate the potential role of γ-tocopherol in the aging process, we examined the associations of serum γ-tocopherol levels with all-cause and cause-specific mortality.

Subjects/methods: Among participants in the biorepository subcohort of the Multiethnic Cohort Study, pre-cancer diagnostic serum γ-tocopherol levels were measured in a subset of 3904 men and 4461 women. Of these, 22.7% of men and 13.5% of women died during a mean follow-up time of 9.6 ± 2.6 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for mortality associated with γ-tocopherol were estimated by Cox proportional hazards regression.

Results: Positive associations of serum γ-tocopherol with all-cause, cancer, and cardiovascular disease mortality (CVD) (P < 0.05) were detected after adjusting for age, race/ethnicity, and serum cholesterol levels. The respective HRs (95% CIs) for the highest versus the lowest sex-specific γ-tocopherol quartile were 1.43 (1.17-1.74), 1.79 (1.22-2.64), and 1.52 (1.10-2.11) for men and 1.58 (1.25-2.00), 1.59 (1.05-2.41), and 1.59 (1.07-2.37) for women. Associations remained significant for all-cause mortality among women after further adjusting for smoking variables and history of cancer, CVD, diabetes, and hypertension at cohort entry (highest vs. lowest γ-tocopherol quartile: HR = 1.38; 95% CI = 1.08-1.75; P = 0.005). Overall, associations with all-cause mortality were consistent across race/ethnicity and were significant in three of ten sex-specific racial/ethnic groups in the fully adjusted models, with no interactions between ethnicity and γ-tocopherol.

Conclusions: The positive association between γ-tocopherol and mortality suggests a potential physiological role for γ-tocopherol in response to pathological conditions.
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http://dx.doi.org/10.1038/s41430-019-0460-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930982PMC
January 2020

Fecal Microbial Diversity and Structure Are Associated with Diet Quality in the Multiethnic Cohort Adiposity Phenotype Study.

J Nutr 2019 09;149(9):1575-1584

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Background: Variation in gut microbial community structure is partly attributed to variations in diet. A priori dietary indexes capture diet quality and have been associated with chronic disease risk.

Objectives: The aim of this study was to examine the association of diet quality, as assessed by the Healthy Eating Index, Alternative Healthy Eating Index-2010, alternate Mediterranean Diet, and the Dietary Approaches to Stop Hypertension Trial, with measures of fecal microbial community structure assessed in the Adiposity Phenotype Study (APS), an ethnically diverse study population with varied food intakes.

Methods: Multiethnic Cohort Study members completed a validated quantitative food frequency questionnaire (QFFQ) at cohort entry (1993-1996) and, for the APS subset, at clinic visit (2013-2015), when they also provided a stool sample. DNA was extracted from stool, and the V1-V3 region of the 16S rRNA gene was amplified and sequenced. Dietary index scores were computed based on the QFFQ and an extensive nutritional database. Using linear regression adjusted for relevant covariates, we estimated associations of dietary quality with microbiome measures and computed adjusted mean values of microbial measures by tertiles of dietary index scores.

Results: The 858 men and 877 women of white, Japanese American, Latino, Native Hawaiian, and African American ancestry had a mean age of 69.2 years at stool collection. Alpha diversity according to the Shannon index increased by 1-2% across tertiles of all 4 diet indexes measured at clinic visit. The mean relative abundance of the phylum Actinobacteria was 13-19% lower with higher diet quality across all 4 indexes (difference between tertile 3 and tertile 1 divided by tertile 1). Of the 104 bacterial genera tested, 21 (primarily from the phylum Firmicutes) were positively associated with at least 1 index after Bonferroni adjustment.

Conclusion: Diet quality was strongly associated with fecal microbial alpha diversity and beta diversity and several genera previously associated with human health.
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http://dx.doi.org/10.1093/jn/nxz065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862930PMC
September 2019

Smoking, Alcohol, and Biliary Tract Cancer Risk: A Pooling Project of 26 Prospective Studies.

J Natl Cancer Inst 2019 12;111(12):1263-1278

Background: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear.

Methods: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided.

Results: Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all Ptrend < .01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; Ptrend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; Ptrend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers.

Conclusions: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.
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http://dx.doi.org/10.1093/jnci/djz103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910180PMC
December 2019

Anthropometric Risk Factors for Cancers of the Biliary Tract in the Biliary Tract Cancers Pooling Project.

Cancer Res 2019 08 21;79(15):3973-3982. Epub 2019 May 21.

Department of Epidemiology and Biostatistics, School of Public Health, Indiana University Bloomington, Bloomington, Indiana.

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 (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs 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/m increase in BMI, 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. SIGNIFICANCE: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-0459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759233PMC
August 2019

Interethnic differences in pancreatic cancer incidence and risk factors: The Multiethnic Cohort.

Cancer Med 2019 07 8;8(7):3592-3603. Epub 2019 May 8.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

While disparity in pancreatic cancer incidence between blacks and whites has been observed, few studies have examined disparity in other ethnic minorities. We evaluated variations in pancreatic cancer incidence and assessed the extent to which known risk factors account for differences in pancreatic cancer risk among African Americans, Native Hawaiians, Japanese Americans, Latino Americans, and European Americans in the Multiethnic Cohort Study. Risk factor data were obtained from the baseline questionnaire. Cox regression was used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for pancreatic cancer associated with risk factors and ethnicity. During an average 16.9-year follow-up, 1,532 incident pancreatic cancer cases were identified among 184,559 at-risk participants. Family history of pancreatic cancer (RR 1.97, 95% CI 1.50-2.58), diabetes (RR 1.32, 95% CI 1.14-1.54), body mass index ≥30 kg/m (RR 1.25, 95% CI 1.08-1.46), current smoking (<20 pack-years RR 1.43, 95% CI 1.19-1.73; ≥20 pack-years RR 1.76, 95% CI 1.46-2.12), and red meat intake (RR 1.17, 95% CI 1.00-1.36) were associated with pancreatic cancer. After adjustment for these risk factors, Native Hawaiians (RR 1.60, 95% CI 1.30-1.98), Japanese Americans (RR 1.33, 95% CI 1.15-1.54), and African Americans (RR 1.20, 95% CI 1.01-1.42), but not Latino Americans (RR 0.90, 95% CI 0.76-1.07), had a higher risk of pancreatic cancer compared to European Americans. Interethnic differences in pancreatic cancer risk are not fully explained by differences in the distribution of known risk factors. The greater risks in Native Hawaiians and Japanese Americans are new findings and elucidating the causes of these high rates may improve our understanding and prevention of pancreatic cancer.
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http://dx.doi.org/10.1002/cam4.2209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601579PMC
July 2019

Propensity for Intra-abdominal and Hepatic Adiposity Varies Among Ethnic Groups.

Gastroenterology 2019 03 13;156(4):966-975.e10. Epub 2018 Nov 13.

University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii.

Background & Aims: 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.

Methods: 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/m. 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1053/j.gastro.2018.11.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409195PMC
March 2019

Alcohol Intake and Colorectal Cancer Risk in the Multiethnic Cohort Study.

Am J Epidemiol 2019 01;188(1):67-76

Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.

To investigate the association of alcohol intake with colorectal cancer risk according to race/ethnicity as well as sex, lifestyle-related factors, alcoholic beverage type, and anatomical subsite, we analyzed data from 190,698 black, Native Hawaiian, Japanese-American, Latino, and white persons in Hawaii and California in the Multiethnic Cohort Study, with 4,923 incident cases during a 16.7-year follow-up period (1993-2013). In multivariate Cox regression models, the hazard ratio was 1.16 (95% confidence interval (CI): 1.01, 1.34) for 15.0-29.9 g/day of alcohol and 1.28 (95% CI: 1.12, 1.45) for ≥30.0 g/day among men, and 1.06 (95% CI: 0.85, 1.32) and 1.15 (95% CI: 0.92, 1.43), respectively, among women, compared with nondrinkers (P for heterogeneity according to sex = 0.74). An increased risk was apparent among Native Hawaiians, Japanese Americans, Latinos, and white persons and among individuals with body mass index <25.0 (calculated as weight (kg)/height (m)2), never-users of nonsteroidal antiinflammatory drugs, and those with lower intake of dietary fiber and folate. Beer and wine, but not liquor, consumption was positively related to colorectal cancer risk. The association was stronger for rectum and left-colon tumors than for right-colon tumors. Our findings suggest that the positive association between alcohol and colorectal cancer varies according to race/ethnicity, lifestyle factors, alcoholic beverage type, and anatomical subsite of tumors.
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http://dx.doi.org/10.1093/aje/kwy208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321802PMC
January 2019

Temporal Variability and Stability of the Fecal Microbiome: The Multiethnic Cohort Study.

Cancer Epidemiol Biomarkers Prev 2019 01 11;28(1):154-162. Epub 2018 Sep 11.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Background: Measurement reliability and biological stability need to be considered when developing sampling protocols for population-based fecal microbiome studies.

Methods: Stool samples were collected biannually over a 2-year period and sequenced for the V1-V3 region of the 16S rRNA gene in 50 participants from the Multiethnic Cohort Study. We evaluated the temporal stability of the fecal microbiome on a community level with permutational multivariate analysis of variance (PERMANOVA), as well as on taxa and diversity measures with intraclass correlation coefficients.

Results: Interindividual differences were the predominant source of fecal microbiome variation, and variation within individual was driven more by changing abundances than by the complete loss or introduction of taxa. Phyla and diversity measures were reliable over the 2 years. Most genera were stable over time, although those with low abundances tended to be more dynamic. Reliability was lower among participants who used antibiotics, with the greatest difference seen in samples taken within 1 month of reported use.

Conclusions: The fecal microbiome as a whole is stable over a 2-year period, although certain taxa may exhibit more temporal variability.

Impact: When designing large epidemiologic studies, a single sample is sufficient to capture the majority of the variation in the fecal microbiome from 16S rRNA gene sequencing, while multiple samples may be needed for rare or less-abundant taxa.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-0348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625800PMC
January 2019

Diet quality measured by four a priori-defined diet quality indices is associated with lipid-soluble micronutrients in the Multiethnic Cohort Study (MEC).

Eur J Clin Nutr 2019 05 2;73(5):703-713. Epub 2018 Aug 2.

Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.

Background/objectives: This study examined the long-term relation of lipid-soluble micronutrients with diet quality as assessed by four a priori-defined dietary patterns.

Subjects/methods: In a prospective design, nutritional biomarkers (carotenoids, tocopherols, retinol, and coenzyme Q10) were measured using a validated HPLC-based assay. General linear models were applied to obtain covariate-adjusted means of biomarkers for tertiles of four a priori diet quality indices: Healthy Eating Index (HEI) 2010, Alternative HEI (AHEI) 2010, Alternate Mediterranean Diet Score (aMED), and Dietary Approaches to Stop Hypertension (DASH). For a subcohort of 8367 participants within the Multiethnic Cohort (MEC), diet was assessed by a validated quantitative food frequency questionnaire in 1993-96 and serum was collected in 2001-06.

Results: Participants with the highest diet-quality scores had significantly higher serum concentrations of all carotenoids, total tocopherols, and α-tocopherol, whereas γ-tocopherol was inversely associated with diet quality. Adjusted means for the lowest vs. highest tertile of HEI 2010 were 1.2 vs. 1.5 mg/L for total carotenoids, 11.4 vs. 12.3 mg/L for total tocopherols, and 1.9 vs. 1.6 mg/L for γ-tocopherol (p < 0.0001). The associations for the other dietary indices were similar; no indication for sex and ethnic differences was detected. Vegetable and fruit components were major predictors of most circulating micronutrients, but most other components were also associated.

Conclusions: Higher diet-quality scores measured by four a priori diet quality indices were significantly associated higher serum concentrations of carotenoids and α-tocopherol, whereas γ-tocopherol was inversely associated with diet quality.
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http://dx.doi.org/10.1038/s41430-018-0272-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359995PMC
May 2019

Pancreatic Cancer Following Incident Diabetes in African Americans and Latinos: The Multiethnic Cohort.

J Natl Cancer Inst 2019 01;111(1):27-33

Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA.

Background: Diabetes has been proposed to be a risk factor for and a consequence of pancreatic cancer (PC). The relationship between recent-onset diabetes and PC is not well understood, and data in minorities are sparse. We examined the relationships between recent-onset diabetes and PC incidence in African Americans and Latinos in the Multiethnic Cohort.

Methods: A total of 48 995 African Americans and Latinos without prior diabetes and cancer at baseline (1993-1996) were included in the study. Questionnaires, Medicare data, and California hospital discharge files were used to identify new diabetes diagnoses. Cox regressions were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer associated with diabetes and with diabetes duration.

Results: A total of 15 833 (32.3%) participants developed diabetes between baseline and 2013. A total of 408 incident PC cases were identified during follow-up. Diabetes was associated with PC (HRage75 = 2.39, 95% CI = 1.91 to 2.98). Individuals with recent-onset diabetes (within three or fewer years of PC diagnosis) had a greater risk compared with those with long-term diabetes across all ages. The HRage75 for recent-onset diabetes was 4.08 (95% CI = 2.76 to 6.03) in Latinos and 3.38 (95% CI = 2.30 to 4.98) in African Americans.

Conclusions: Diabetes was associated with a more than twofold higher risk of PC in African Americans and Latinos, but recent-onset diabetes was associated with a 2.3-fold greater increase in risk of PC than long-standing diabetes. Our findings support the hypothesis that recent-onset diabetes is a manifestation of PC and that long-standing diabetes is a risk factor for this malignancy.
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http://dx.doi.org/10.1093/jnci/djy090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335114PMC
January 2019

Portion Sizes from 24-Hour Dietary Recalls Differed by Sex among Those Who Selected the Same Portion Size Category on a Food Frequency Questionnaire.

J Acad Nutr Diet 2018 09 8;118(9):1711-1718. Epub 2018 May 8.

Background: Accounting for sex differences in food portions may improve dietary measurement; however, this factor has not been well examined.

Objective: The aim of this study was to examine sex differences in reported food portions from 24-hour dietary recalls (24HDRs) among those who selected the same portion size category on a quantitative food frequency questionnaire (QFFQ).

Design: This study was conducted with a cross-sectional design.

Participants/setting: Participants (n=319) were members of the Hawaii-Los Angeles Multiethnic Cohort who completed three 24HDRs and a QFFQ in a calibration study conducted in 2010 and 2011.

Main Outcome Measures: Portions of individual foods reported from 24HDRs served as the outcome measures.

Statistical Analyses Performed: Mean food portions from 24HDRs were compared between men and women who reported the same portion size on the QFFQ, after adjustment for race/ethnicity using a linear regression model. Actual amount and the assigned amount of the selected portion size in the QFFQ were compared using one-sample t test for men and women separately.

Results: Of 163 food items with portion size options listed in the QFFQ, 32 were reported in 24HDRs by ≥20 men and ≥20 women who selected the same portion size in the QFFQ. Although they chose the same portion size on the QFFQ, mean intake amounts from 24HDRs were significantly higher for men than for women for "beef/lamb/veal," "white rice," "brown/wild rice," "lettuce/tossed salad," "eggs cooked/raw," "whole wheat/rye bread," "buns/rolls," and "mayonnaise in sandwiches." For men, mean portions of 14 items from the 24HDRs were significantly different from the assigned amounts for QFFQ items (seven higher and seven lower), whereas for women, mean portions of 14 items were significantly lower from the assigned amounts (with five significantly higher).

Conclusions: These sex differences in reported 24HDR food portions-even among participants who selected the same portion size on the QFFQ-suggest that the use of methods that account for differences in the portions consumed by men and women when QFFQs are quantified may provide more accurate absolute dietary intakes.
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http://dx.doi.org/10.1016/j.jand.2018.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610234PMC
September 2018

Self-reported dietary flavonoid intake and serum markers of inflammation: the multiethnic cohort.

Cancer Causes Control 2018 06 18;29(6):601-607. Epub 2018 Apr 18.

Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.

Purpose: To examine if dietary intake of foods rich in flavonoids, which have been shown to be inversely associated with chronic diseases, is associated with inflammatory processes.

Methods: This analysis includes controls of case-control studies nested within the Multiethnic Cohort (MEC) who completed a validated food frequency questionnaire at cohort entry. Biomarkers were assessed in blood donated during follow-up (mean = 9.6 years). We used multivariate linear regression adjusted for potential confounders to estimate associations between intake of flavanones, flavonols, and isoflavones and levels of adiponectin, leptin, C-reactive protein, interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α.

Results: Among the 1,287 participants, the respective median intakes of flavanones, flavonols, and isoflavones were 26.5, 12.4, and 1.3 mg/day at cohort entry. With the exception of flavanone intake, which was statistically significantly inversely associated with adiponectin (p = 0.01) and IL-6 concentrations (p = 0.01), none of the examined flavonoids was related with levels of adipokines or inflammatory markers. Heterogeneity by ethnicity was only observed for flavonol intake and IL-10 (p = 0.04) and may be the result of multiple testing. These null findings were confirmed in a subset of participants who completed a second dietary history within 2.6 years of blood draw.

Conclusion: The current results do not support a consistent association between dietary intake of flavonoids and markers of inflammatory processes.
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http://dx.doi.org/10.1007/s10552-018-1034-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180210PMC
June 2018
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