Publications by authors named "Lynne R Wilkens"

431 Publications

Genome-wide association study of pancreatic fat: The Multiethnic Cohort Adiposity Phenotype Study.

PLoS One 2021 30;16(7):e0249615. Epub 2021 Jul 30.

University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America.

Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited. This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS). Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10-8) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10-8) were associated with percent pancreatic fat on the log scale. Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%). Rs73449607 was also associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls). Rs73449607 is located in an intergenic region between GSX1 and PLUTO, and rs79967607 is in intron 1 of EPM2A. PLUTO, a lncRNA, regulates transcription of an adjacent gene, PDX1, that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production. If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249615PLOS
July 2021

Race, ethnicity, community-level socioeconomic factors, and risk of COVID-19 in the United States and the United Kingdom.

EClinicalMedicine 2021 Aug 17;38:101029. Epub 2021 Jul 17.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, 100 Cambridge Street, 15th Floor, Boston, MA 02114, USA.

Background: There is limited prior investigation of the combined influence of personal and community-level socioeconomic factors on racial/ethnic disparities in individual risk of coronavirus disease 2019 (COVID-19).

Methods: We performed a cross-sectional analysis nested within a prospective cohort of 2,102,364 participants from March 29, 2020 in the United States (US) and March 24, 2020 in the United Kingdom (UK) through December 02, 2020 via the COVID Symptom Study smartphone application. We examined the contribution of community-level deprivation using the Neighborhood Deprivation Index (NDI) and the Index of Multiple Deprivation (IMD) to observe racial/ethnic disparities in COVID-19 incidence. ClinicalTrials.gov registration: NCT04331509.

Findings: Compared with non-Hispanic White participants, the risk for a positive COVID-19 test was increased in the US for non-Hispanic Black (multivariable-adjusted odds ratio [OR], 1.32; 95% confidence interval [CI], 1.18-1.47) and Hispanic participants (OR, 1.42; 95% CI, 1.33-1.52) and in the UK for Black (OR, 1.17; 95% CI, 1.02-1.34), South Asian (OR, 1.39; 95% CI, 1.30-1.49), and Middle Eastern participants (OR, 1.38; 95% CI, 1.18-1.61). This elevated risk was associated with living in more deprived communities according to the NDI/IMD. After accounting for downstream mediators of COVID-19 risk, community-level deprivation still mediated 16.6% and 7.7% of the excess risk in Black compared to White participants in the US and the UK, respectively.

Interpretation: Our results illustrate the critical role of social determinants of health in the disproportionate COVID-19 risk experienced by racial and ethnic minorities.
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http://dx.doi.org/10.1016/j.eclinm.2021.101029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285255PMC
August 2021

Biomarker-Based Visceral Adiposity Score and Incident Type 2 Diabetes in the Multiethnic Cohort.

Ann Epidemiol 2021 Jul 20. Epub 2021 Jul 20.

University of Hawaii Cancer Center, Honolulu, HI.

Purpose: Visceral adipose tissue (VAT) may be more important than subcutaneous fat in type 2 diabetes (T2D) etiology. We examined a VAT score developed in reference to MRI measurement of VAT in the Multiethnic Cohort (MEC) as a risk factor for incident T2D.

Methods: Two nested case-control studies of cancer allowed calculation of the VAT score based on anthropometric measures and eight biomarkers among 2,556 participants without T2D. Incident cases were identified from Medicare linkages and self-reports after blood draws in 2001-2006. Cox regression with age as time metric was applied to estimate the association of the VAT score with T2D.

Results: During 10.1±2.4 years, 355 incident T2D cases were identified. VAT scores were higher in T2D cases than among those without disease (5.06±0.43 vs. 4.95±0.41; p<0.0001) and significantly associated with T2D (HR=2.70; 95%CI 1.60, 4.58 per unit) with similar values in men (HR=2.99; 95%CI 1.03, 8.73) and women (HR=2.61; 95%CI 1.39, 4.91). A significant association was observed in all five ethnic groups but only statistically significant among Japanese Americans (HR=6.24; 95%CI 2.34, 16.68).

Conclusions: These findings support that VAT as estimated by a biomarker-based score predicts T2D incidence beyond BMI in particular among older adults of Japanese ancestry.
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http://dx.doi.org/10.1016/j.annepidem.2021.07.002DOI Listing
July 2021

University of Hawai'i Cancer Center Connection: Pacific Tracker (PacTrac) Version 3.1 Diet and Physical Activity Assessment Tool for the Pacific Region.

Hawaii J Health Soc Welf 2021 Jul;80(7):165-168

University of Hawai'i Cancer Center, Honolulu, HI (MEE, YOJ, GJJ, CB, LRW).

The Pacific Tracker (PacTrac) is a web-based diet and physical activity assessment program created to analyze dietary recall or dietary record data from the Pacific region. Version 3.1 modifications make the tool available for public use (under check it out) to enter, analyze, view and print out data; and for research use, for saving and downloading of multiple entries in a research mode. PacTrac 3.1 (https://nappactrac31.ctahr.hawaii.edu/default.htm) is managed through the Children's Healthy Living Center of Excellence (CHL Center) at the College of Tropical Agriculture and Human Resources at the University of Hawai'i, in collaboration with the University of Hawai'i Cancer Center.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280357PMC
July 2021

Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies.

Am J Clin Nutr 2021 Jul 13. Epub 2021 Jul 13.

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

Background: Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis.

Objectives: The objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC.

Methods: We conducted a pathway analysis of the hepcidin-regulating genes using single nucleotide polymorphism (SNP) summary statistics generated from 4 genome-wide association studies in 2 large consortium studies using the summary data-based adaptive rank truncated product method. Our population consisted of 9253 PDAC cases and 12,525 controls of European descent. Our analysis included 11 hepcidin-regulating genes [bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 6 (BMP6), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), hepcidin (HAMP), homeostatic iron regulator (HFE), hemojuvelin (HJV), nuclear factor erythroid 2-related factor 2 (NRF2), ferroportin 1 (SLC40A1), transferrin receptor 1 (TFR1), and transferrin receptor 2 (TFR2)] and their surrounding genomic regions (±20 kb) for a total of 412 SNPs.

Results: The hepcidin-regulating gene pathway was significantly associated with PDAC (P = 0.002), with the HJV, TFR2, TFR1, BMP6, and HAMP genes contributing the most to the association.

Conclusions: Our results support that genetic susceptibility related to the hepcidin-regulating gene pathway is associated with PDAC risk and suggest a potential role of iron metabolism in pancreatic carcinogenesis. Further studies are needed to evaluate effect modification by intake of iron-rich foods on this association.
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http://dx.doi.org/10.1093/ajcn/nqab217DOI Listing
July 2021

Development and Validation of a Risk Prediction Tool for Second Primary Lung Cancer.

J Natl Cancer Inst 2021 Jul 13. Epub 2021 Jul 13.

Quantitative Sciences Unit, Stanford University School of Medicine, Stanford, CA, USA.

Background: With advancing therapeutics, lung cancer (LC) survivors are rapidly increasing in number. While mounting evidence suggests LC survivors have high risk of second primary lung cancer (SPLC), there is no validated prediction tool available for clinical use to identify high-risk LC survivors for SPLC.

Methods: Using data from 6,325 ever-smokers in the Multiethnic Cohort (MEC) diagnosed with initial primary lung cancer (IPLC) in 1993-2017, we developed a prediction model for 10-year SPLC risk after IPLC diagnosis using cause-specific Cox regression. We evaluated the model's clinical utility using decision curve analysis and externally validated it using two population-based data, PLCO and NLST, that included 2,963 and 2,844 IPLC (101 and 93 SPLC cases), respectively.

Results: Over 14,063 person-years, 145 (2.3%) developed SPLC in MEC. Our prediction model demonstrated a high predictive accuracy (Brier score = 2.9, 95% confidence interval [CI] = 2.4-3.3) and discrimination (AUC = 81.9%, 95% CI = 78.2%-85.5%) based on bootstrap validation in MEC. Stratification by the estimated risk quartiles showed that the observed SPLC incidence was statistically significantly higher in the 4th versus 1st quartile (9.5% versus 0.2%; P < .001). Decision curve analysis indicated that in a wide range of 10-year risk thresholds from 1% to 20%, the model yielded a larger net-benefit versus hypothetical all-screening or no-screening scenarios. External validation using PLCO and NLST showed an AUC of 78.8% (95% CI = 74.6%-82.9%) and 72.7% (95% CI = 67.7%-77.7%), respectively.

Conclusions: We developed and validated a SPLC prediction model based on large population-based cohorts. The proposed prediction tool can help identify high-risk LC patients for SPLC and can be incorporated into clinical decision-making for SPLC surveillance and screening.
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http://dx.doi.org/10.1093/jnci/djab138DOI Listing
July 2021

Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults.

Sci Rep 2021 Jul 5;11(1):13805. Epub 2021 Jul 5.

Duke - NUS Medical School, Singapore, Singapore.

Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40-80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was - 0.91 standard-deviations lower in women than men (95%CI - 0.98; - 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p < 0.05) association with time since smoking cessation was observed for 8 markers, including C-reactive protein, kynurenine, choline, and total homocysteine. We conclude that most blood biomarkers show small variations across demographic characteristics. Patterns by smoking status point to normalization of multiple physiological processes after smoking cessation.
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http://dx.doi.org/10.1038/s41598-021-93214-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257595PMC
July 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

Determination of Child Waist Circumference Cut Points for Metabolic Risk Based on Acanthosis Nigricans, the Children's Healthy Living Program.

Prev Chronic Dis 2021 Jun 24;18:E64. Epub 2021 Jun 24.

Department of Human Nutrition, Food and Animal Science, College of Tropical Agriculture and Human Resources, University of Hawai'i at Mānoa, Honolulu, Hawai'i.

Introduction: Waist circumference is a common anthropometric measure for predicting abdominal obesity and insulin resistance. We developed optimal waist circumference cut points for children aged 2 to 8 years in the US-Affiliated Pacific (USAP) region based on the relationship of waist circumference and acanthosis nigricans in this population.

Methods: We conducted a cross-sectional analysis from the Children's Healthy Living Program's 2012-2013 data on 4,023 children. We used receiver-operating characteristic analysis to determine the sensitivity and specificity for acanthosis nigricans across waist circumference, by sex and age. We determined optimal waist circumference cutoff points corresponding to Youden index (J), (equal to [sensitivity + specificity] - 1), with acanthosis nigricans. We compared these cut points with the 90th percentile.

Results: The 90th-percentile cut points for boys aged 2 to 5 years (58.15 cm) and 6 to 8 years (71.63 cm) were slightly higher than for girls in both age groups (aged 2-5 y, 57.97 cm; 6-8 y: 70.37 cm). The optimal cut points (corresponding to the highest sensitivity and specificity) were as follows: for boys aged 2 to 5 years, 90th percentile (58.25 cm; sensitivity, 48.0%; specificity, 91.5%); for boys aged 6 to 8 years, 78th percentile (63.59 cm; sensitivity, 86.8%; specificity, 82.8%); for girls aged 2 to 5 years, 62nd percentile (53.27 cm; sensitivity, 71.4%; specificity, 63.1%), and for girls aged 6 to 8 years, 80th percentile (63.63 cm; sensitivity, 55.4%; specificity, 82.9%).

Conclusion: Among USAP children, waist circumference was a reasonable predictor for acanthosis nigricans. Further analysis is warranted to examine causes of acanthosis nigricans at lower-than-expected waist circumference percentiles. The cut points can be used for early detection of metabolic risk.
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http://dx.doi.org/10.5888/pcd18.210021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269744PMC
June 2021

The gut microbiome and type 2 diabetes status in the Multiethnic Cohort.

PLoS One 2021 23;16(6):e0250855. Epub 2021 Jun 23.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250855PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221508PMC
June 2021

Diet Quality and Risk of Lung Cancer in the Multiethnic Cohort Study.

Nutrients 2021 May 12;13(5). Epub 2021 May 12.

Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.

Diet quality, assessed by the Healthy Eating Index-2015 (HEI-2015), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED) score, the Dietary Approaches to Stop Hypertension (DASH) score, and the Dietary Inflammatory Index (DII), was examined in relation to risk of lung cancer in the Multiethnic Cohort Study. The analysis included 179,318 African Americans, Native Hawaiians, Japanese Americans, Latinos, and Whites aged 45-75 years, with 5350 incident lung cancer cases during an average follow-up of 17.5 ± 5.4 years. In multivariable Cox models comprehensively adjusted for cigarette smoking, the hazard ratios (95% confidence intervals) for the highest vs. lowest quality group based on quintiles were as follows: 0.85 (0.77-0.93) for HEI-2015; 0.84 (0.77-0.92) for AHEI-2010; 0.83 (0.76-0.91) for aMED; 0.83 (0.73-0.91) for DASH; and 0.90 (0.82-0.99) for DII. In histological cell type-specific analyses, the inverse association was stronger for squamous cell carcinoma than for adeno-, small cell, and large cell carcinomas for all indexes. There was no indication of differences in associations by sex, race/ethnicity, and smoking status. These findings support that high-quality diets are associated with lower risk of lung cancer, especially squamous cell carcinomas, in a multiethnic population.
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http://dx.doi.org/10.3390/nu13051614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151689PMC
May 2021

A Dietary Supplement Frequency Questionnaire Correctly Ranks Nutrient Intakes in US Older Adults When Compared to a Comprehensive Dietary Supplement Inventory.

J Nutr 2021 May 26. Epub 2021 May 26.

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

Background: Dietary supplements are commonly taken by adults in the United States and can contribute substantially to daily nutrient intakes. Short supplement-use questionnaires are often used in dietary surveys, but their accuracy has not been well studied.

Objectives: The primary objective was to evaluate the accuracy of a short, self-administered supplement frequency questionnaire (SFQ) relative to a comprehensive 1-y inventory of supplement use. A secondary objective was to compare SFQ responses for participants in the intensive measurement study to those from a control group to investigate a possible research participation effect.

Methods: The Supplement Reporting study enrolled 1029 older adults in 2005-2006, with a mean age of 67.8 y, who participated in the Multiethnic Cohort and reported regular use of dietary supplements. Of these, 375 were interviewed quarterly to collect detailed information on types and amounts of dietary supplements used, while 654 served as the control group. All participants completed 2 SFQs, 1 y apart.

Results: Agreement between the 2 instruments in use at least weekly ranged from 88% to 97% for 15 of 16 supplement types, with a lower agreement of 74% for vitamin D. The correlations of nutrient intakes from supplements between the 2 instruments were high, ranging from 0.48 to 0.75, except for iron (r = 0.29). However, mean nutrient intakes as reported on the SFQ were higher than intakes from the inventory for most nutrients, sometimes twice as high. Nutrient intakes based on the SFQ were similar for the inventory and control groups, at both baseline and the end of the study.

Conclusions: A self-administered short SFQ can be used in large surveys to identify participants who use 16 categories of dietary supplements at least once a week and can correctly rank participant intakes of nutrients. However, the SFQ does not accurately estimate absolute levels of nutrient intakes from supplements.
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http://dx.doi.org/10.1093/jn/nxab140DOI Listing
May 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
May 2021

Risk of breast cancer and prediagnostic urinary excretion of bisphenol A, triclosan and parabens: The Multiethnic Cohort Study.

Int J Cancer 2021 May 20. Epub 2021 May 20.

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

Exposure to bisphenol A (BPA), triclosan and parabens is widespread but their impact on breast cancer risk remains unclear. This nested case-control study investigated endocrine-disrupting chemicals (EDCs) and breast cancer risk within the Multiethnic Cohort (MEC). We measured prediagnostic urinary BPA, triclosan and parabens in 1032 postmenopausal women with breast cancer (48 African American, 77 Latino, 155 Native Hawaiian, 478 Japanese American and 274 White) and 1030 individually matched controls, using a sensitive and validated liquid chromatography mass spectrometry assay. Conditional logistic regression was used to examine risk with these EDCs with adjustment for creatinine and potential confounders. In all women, breast cancer risk was not associated with BPA (P  = 0.53) and was inversely associated with triclosan (OR  = 0.83, 95% CI: 0.66-1.04, P  = 0.045) and total parabens (OR  = 0.77, 95% CI: 0.62-0.97, P  = 0.03). While risk of hormone receptor positive (HR+) cancer was 20% to 23% lower among women in the upper two tertiles of paraben exposure (P  = 0.02), risk of HR negative (HR-) was reduced 27% but only among those in the upper tertile of exposure. Although risk associations did not differ significantly by ethnicity or by body mass index (BMI), the inverse association with triclosan was observed mainly among overweight/obese women (OR  = 0.76, 95% CI: 0.56-1.02, P  = 0.02). In summary, breast cancer risk in a multiethnic population was unrelated to BPA and was weakly inversely associated with triclosan and paraben exposures. Studies with multiple urine samples collected before breast cancer diagnosis are needed to further investigate these EDCs and breast cancer risk.
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http://dx.doi.org/10.1002/ijc.33692DOI Listing
May 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 May 8. Epub 2021 May 8.

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
May 2021

Red meat consumption, cooking mutagens, NAT1/2 genotypes and pancreatic cancer risk in two ethnically diverse prospective cohorts.

Int J Cancer 2021 Apr 12. Epub 2021 Apr 12.

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

There is limited evidence on the association between red meat consumption and pancreatic cancer among ethnic minorities. We assessed this relationship in two large prospective cohorts: the Multiethnic Cohort Study (MEC) and the Southern Community Cohort Study (SCCS). Demographic, dietary and other risk factor data were collected at cohort entry. Red meat intake was assessed using cohort-specific validated food frequency questionnaires. Incident pancreatic cancer cases were identified via linkages to state cancer registries. Cox regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association of red meat intake with pancreatic cancer risk in each cohort. We performed additional analyses to evaluate cooking methods, mutagens and effect modification by NAT1/2 genotypes. From a total of 184 542 (MEC) and 66 793 (SCCS) at-risk participants, we identified 1618 (MEC) and 266 (SCCS) incident pancreatic cancer cases. Red meat consumption was associated with pancreatic cancer risk in the MEC (RR 1.18, 95% CI 1.02-1.37) and with borderline statistical significance in the SCCS (RR 1.31, 95% CI 0.93-1.86). This association was significant in African Americans (RR 1.49, 95% CI 1.06-2.11) and Latinos (RR 1.44, 95% CI 1.02-2.04) in the MEC, and among African Americans (RR 1.55, 95% CI 1.03-2.33) in the SCCS. NAT2 genotypes appeared to modify the relationship between red meat and pancreatic cancer in the MEC (p = 0.03). Our findings suggest that the associations for red meat may be strongest in African Americans and Latinos. The mechanisms underlying the increased risk for these populations should be further investigated.
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http://dx.doi.org/10.1002/ijc.33598DOI Listing
April 2021

Urinary phthalate exposures and risk of breast cancer: the Multiethnic Cohort study.

Breast Cancer Res 2021 Apr 6;23(1):44. Epub 2021 Apr 6.

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

Background: The epidemiologic evidence from observational studies on breast cancer risk and phthalates, endocrine disrupting chemicals, has been inconsistent. In the only previous study based on pre-diagnostic urinary phthalates and risk of breast cancer, results were null in mostly white women.

Methods: We examined the association between pre-diagnostic urinary phthalates and breast cancer in a nested case-control study within the Multiethnic Cohort (MEC) study, presenting the first data from five major racial/ethnic groups in the USA. We measured 10 phthalate metabolites and phthalic acid, using a sensitive liquid chromatography mass spectrometry assay on 1032 women with breast cancer (48 African Americans, 77 Latinos, 155 Native Hawaiians, 478 Japanese Americans, and 274 Whites) and 1030 matched controls. Conditional logistic regression was used to examine risk with individual metabolites and ratios of primary (MEHP, mono-2-ethylhexyl-phthalate) to secondary (MEHHP, mono(2-ethyl-5-hydroxyhexyl); MEOHP, mono(2-ethyl-5-oxohexy)) metabolites of di-2-ethylhexyl phthalate (DEHP), a widely used plasticizer. In addition, we investigated risk associations with high (∑HMWP) and low molecular weight (∑LMWP) phthalates, as well as total phthalates which included high and low molecular weight phthalates with phthalic acid (∑LMHMPA) or without phthalic acid in molar ratios (∑LMHM) and adjusted for creatinine and potential confounders.

Results: Among all women, breast cancer risk was higher for those in tertile 2 and tertile 3 of primary to secondary metabolites of DEHP (MEHP/(MEHHP + MEOHP)) in comparison to those in tertile 1; the respective odds ratios were 1.32 (95% CI 1.04-1.68) and 1.26 (95% CI 0.96-1.66) (P = 0.05). Risk among Native Hawaiian women increased with exposures to eight of ten individual phthalates and total phthalates (∑LMHMPA OR = 2.66, 95% CI 1.39-5.12, P = 0.001). In analysis by hormone receptor (HR) status, exposure above the median of ∑LMWP was associated with an increased risk of HR-positive breast cancer (OR = 1.30, 95% CI 1.05-1.60) while above the median exposure to phthalic acid was associated with an increased risk of HR-negative breast cancer (OR = 1.59, 95% CI 1.01-2.48).

Conclusions: Further investigations of suggestive associations of elevated breast cancer risk with higher ratios of primary to secondary metabolites of DEHP, and differences in risk patterns by race/ethnicity and HR status are warranted.
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http://dx.doi.org/10.1186/s13058-021-01419-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025373PMC
April 2021

Racial/ethnic differences in anthropometric and hormone-related factors and endometrial cancer risk: the Multiethnic Cohort Study.

Br J Cancer 2021 May 15;124(10):1724-1733. Epub 2021 Mar 15.

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

Background: Anthropometric and hormone-related factors are established endometrial cancer risk factors; however, little is known about the impact of these factors on endometrial cancer risk in non-White women.

Methods: Among 110,712 women participating in the Multiethnic Cohort (MEC) Study, 1150 incident invasive endometrial cancers were diagnosed. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with endometrial cancer risk for race/ethnicity and for risk factors across racial/ethnic groups were calculated.

Results: Having a higher body mass index (BMI) at baseline or age 21 years was strongly associated with increased risk (p race/ethnicity ≥ 0.36). Parity (vs nulliparity) was inversely associated with risk in all the groups except African Americans (p 0.006). Current use of postmenopausal hormones at baseline (PMH-E; vs never use) was associated with increased risk in Whites and Japanese Americans (p 0.002). Relative to Whites, endometrial cancer risk was lower in Japanese Americans and Latinas and non-significantly higher in Native Hawaiians. Risk in African Americans did not differ from that in Whites.

Conclusions: Racial/ethnic differences in endometrial cancer risk were not fully explained by anthropometric or hormone-related risk factors. Further studies are needed to identify reasons for the observed racial/ethnic differences in endometrial cancer risk.
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http://dx.doi.org/10.1038/s41416-021-01292-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111025PMC
May 2021

Tobacco Smoking and Risk of Second Primary Lung Cancer.

J Thorac Oncol 2021 06 17;16(6):968-979. Epub 2021 Mar 17.

Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, California; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California; Department of Neurosurgery, Stanford University School of Medicine, Stanford, California. Electronic address:

Introduction: Lung cancer survivors are at high risk of developing a second primary lung cancer (SPLC). However, SPLC risk factors have not been established and the impact of tobacco smoking remains controversial. We examined the risk factors for SPLC across multiple epidemiologic cohorts and evaluated the impact of smoking cessation on reducing SPLC risk.

Methods: We analyzed data from 7059 participants in the Multiethnic Cohort (MEC) diagnosed with an initial primary lung cancer (IPLC) between 1993 and 2017. Cause-specific proportional hazards models estimated SPLC risk. We conducted validation studies using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 3423 IPLC cases) and European Prospective Investigation into Cancer and Nutrition (N = 4731 IPLC cases) cohorts and pooled the SPLC risk estimates using random effects meta-analysis.

Results: Overall, 163 MEC cases (2.3%) developed SPLC. Smoking pack-years (hazard ratio [HR] = 1.18 per 10 pack-years, p < 0.001) and smoking intensity (HR = 1.30 per 10 cigarettes per day, p < 0.001) were significantly associated with increased SPLC risk. Individuals who met the 2013 U.S. Preventive Services Task Force's screening criteria at IPLC diagnosis also had an increased SPLC risk (HR = 1.92; p < 0.001). Validation studies with the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and European Prospective Investigation into Cancer and Nutrition revealed consistent results. Meta-analysis yielded pooled HRs of 1.16 per 10 pack-years (p < 0.001), 1.25 per 10 cigarettes per day (p < 0.001), and 1.99 (p < 0.001) for meeting the U.S. Preventive Services Task Force's criteria. In MEC, smoking cessation after IPLC diagnosis was associated with an 83% reduction in SPLC risk (HR = 0.17; p < 0.001).

Conclusions: Tobacco smoking is a risk factor for SPLC. Smoking cessation may reduce the risk of SPLC. Additional strategies for SPLC surveillance and screening are warranted.
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http://dx.doi.org/10.1016/j.jtho.2021.02.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159872PMC
June 2021

Association of Sepsis Mortality with Specific Cancer Sites and Treatment Type: The Multiethnic Cohort Study.

J Pers Med 2021 Feb 19;11(2). Epub 2021 Feb 19.

Cancer Center, University of Hawaii, Honolulu, HI 96813, USA.

Sepsis is a severe dysregulated immune response to infection. Sepsis deaths represent 9% of cancer deaths in the U.S. Evidence of the effect of specific cancer sites on sepsis mortality risk remains limited, and no research has evaluated the effect of cancer treatment on the risk of sepsis death. We examined whether cancer sites and treatments differentially affect the risk of sepsis death compared to other-cause mortality, among the 94,784 Hawaii participants in the Multiethnic Cohort, including 29,255 cancer cases, using competing risk Cox proportional hazards regression. Cancer diagnosis at any site was associated with similar increases in sepsis and non-sepsis mortality risk (HR: 3.39 and 3.51, resp.). Colorectal cancer differentially affected the risk of sepsis and non-sepsis mortality with a 40% higher effect on the risk of sepsis death compared with non-sepsis mortality (RRR: 1.40; 95% CI: 1.14-1.72). Lung cancer was associated with a significantly lower increase in sepsis compared to non-sepsis mortality (HR: 1.22 and 3.0, resp.; RRR: 0.39). Radiation therapy had no effect on sepsis mortality but was associated with higher risk of non-sepsis mortality (HR: 0.90 and 1.16, resp.; RRR: 0.76), whereas chemotherapy was associated with higher risk of both sepsis and non-sepsis mortality (HR: 1.31 and 1.21, resp.). We conclude that the risk of sepsis-related mortality is differentially affected by cancer sites and treatments. These associations were consistent across sexes and ethnic groups.
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http://dx.doi.org/10.3390/jpm11020146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922684PMC
February 2021

Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3.

Cancer Res 2021 Jun 11;81(11):3134-3143. Epub 2021 Feb 11.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland.

Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and < 5 × 10 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82-0.93; former smokers 1.00, 95% CI, 0.91-1.07; current smokers 1.25, 95% CI 1.12-1.40, = 3.08 × 10). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 ( = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings. SIGNIFICANCE: This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178175PMC
June 2021

Utility of self-rated adherence for monitoring dietary and physical activity compliance and assessment of participant feedback of the Healthy Diet and Lifestyle Study pilot.

Pilot Feasibility Stud 2021 Feb 11;7(1):48. Epub 2021 Feb 11.

University of Hawai'i Cancer Center, University of Hawaii at Manoa, 701 Ilalo Street, Honolulu, HI, 96813, USA.

Background: We examined the utility of self-rated adherence to dietary and physical activity (PA) prescriptions as a method to monitor intervention compliance and facilitate goal setting during the Healthy Diet and Lifestyle Study (HDLS). In addition, we assessed participants' feedback of HDLS. HDLS is a randomized pilot intervention that compared the effect of intermittent energy restriction combined with a Mediterranean diet (IER + MED) to a Dietary Approaches to Stop Hypertension (DASH) diet, with matching PA regimens, for reducing visceral adipose tissue area (VAT).

Methods: Analyses included the 59 (98%) participants who completed at least 1 week of HDLS. Dietary and PA adherence scores were collected 8 times across 12 weeks, using a 0-10 scale (0 = not at all, 4 = somewhat, and 10 = following the plan very well). Adherence scores for each participant were averaged and assigned to high and low adherence categories using the group median (7.3 for diet, 7.1 for PA). Mean changes in VAT and weight from baseline to 12 weeks are reported by adherence level, overall and by randomization arm. Participants' feedback at completion and 6 months post-intervention were examined.

Results: Mean ± SE, dietary adherence was 6.0 ± 0.2 and 8.2 ± 0.1, for the low and high adherence groups, respectively. For PA adherence, mean scores were 5.9 ± 0.2 and 8.5 ± 0.2, respectively. Compared to participants with low dietary adherence, those with high adherence lost significantly more VAT (22.9 ± 3.7 cm vs. 11.7 ± 3.9 cm [95% CI, - 22.1 to - 0.3]) and weight at week 12 (5.4 ± 0.8 kg vs. 3.5 ± 0.6 kg [95% CI, - 3.8 to - 0.0]). For PA, compared to participants with low adherence, those with high adherence lost significantly more VAT (22.3 ± 3.7 cm vs. 11.6 ± 3.6 cm [95% CI, - 20.7 to - 0.8]). Participants' qualitative feedback of HDLS was positive and the most common response, on how to improve the study, was to provide cooking classes.

Conclusions: Results support the use of self-rated adherence as an effective method to monitor dietary and PA compliance and facilitate participant goal setting. Study strategies were found to be effective with promoting compliance to intervention prescriptions.

Trial Registration: ClinicalTrials.gov Identifier: NCT03639350 . Registered 21st August 2018-retrospectively registered.
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http://dx.doi.org/10.1186/s40814-021-00786-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876789PMC
February 2021

The impact of global and local Polynesian genetic ancestry on complex traits in Native Hawaiians.

PLoS Genet 2021 02 11;17(2):e1009273. Epub 2021 Feb 11.

Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.

Epidemiological studies of obesity, Type-2 diabetes (T2D), cardiovascular diseases and several common cancers have revealed an increased risk in Native Hawaiians compared to European- or Asian-Americans living in the Hawaiian islands. However, there remains a gap in our understanding of the genetic factors that affect the health of Native Hawaiians. To fill this gap, we studied the genetic risk factors at both the chromosomal and sub-chromosomal scales using genome-wide SNP array data on ~4,000 Native Hawaiians from the Multiethnic Cohort. We estimated the genomic proportion of Native Hawaiian ancestry ("global ancestry," which we presumed to be Polynesian in origin), as well as this ancestral component along each chromosome ("local ancestry") and tested their respective association with binary and quantitative cardiometabolic traits. After attempting to adjust for non-genetic covariates evaluated through questionnaires, we found that per 10% increase in global Polynesian genetic ancestry, there is a respective 8.6%, and 11.0% increase in the odds of being diabetic (P = 1.65×10-4) and having heart failure (P = 2.18×10-4), as well as a 0.059 s.d. increase in BMI (P = 1.04×10-10). When testing the association of local Polynesian ancestry with risk of disease or biomarkers, we identified a chr6 region associated with T2D. This association was driven by an uniquely prevalent variant in Polynesian ancestry individuals. However, we could not replicate this finding in an independent Polynesian cohort from Samoa due to the small sample size of the replication cohort. In conclusion, we showed that Polynesian ancestry, which likely capture both genetic and lifestyle risk factors, is associated with an increased risk of obesity, Type-2 diabetes, and heart failure, and that larger cohorts of Polynesian ancestry individuals will be needed to replicate the putative association on chr6 with T2D.
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http://dx.doi.org/10.1371/journal.pgen.1009273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877570PMC
February 2021

Changes in diet quality and body weight over 10 years: the Multiethnic Cohort Study.

Br J Nutr 2021 Jan 14:1-9. Epub 2021 Jan 14.

Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI96813, USA.

High-quality diets have been found to be beneficial in preventing long-term weight gain. However, concurrent changes in diet quality and body weight over time have rarely been reported. We examined the association between 10-year changes in diet quality and body weight in the Multiethnic Cohort Study. Analyses included 53 977 African Americans, Native Hawaiians, Japanese Americans, Latinos and Whites, who completed both baseline (1993-1996, 45-69 years) and 10-year follow-up (2003-2008) surveys including a FFQ and had no history of heart disease or cancer. Using multivariable regression, weight changes were regressed on changes in four diet quality indexes, Healthy Eating Index-2015, Alternative Healthy Eating Index-2010, alternate Mediterranean Diet and Dietary Approaches to Stop Hypertension scores. Mean weight change over 10 years was 1·2 (sd 6·8) kg in men and 1·5 (sd 7·2) kg in women. Compared with stable diet quality (< 0·5 sd change), the greatest increase (≥ 1 sd increase) in the diet scores was associated with less weight gain (by 0·55-1·17 kg in men and 0·62-1·31 kg in women). Smaller weight gain with improvement in diet quality was found in most subgroups by race/ethnicity, baseline age and baseline BMI. The inverse association was stronger in younger age and higher BMI groups. Ten-year improvement in diet quality was associated with a smaller weight gain, which varied by race/ethnicity and baseline age and BMI. Our findings suggest that maintaining a high-quality diet and improving diet quality over time may prevent excessive weight gain.
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http://dx.doi.org/10.1017/S000711452100012XDOI Listing
January 2021

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Nat Genet 2021 01 4;53(1):65-75. Epub 2021 Jan 4.

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
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http://dx.doi.org/10.1038/s41588-020-00748-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148035PMC
January 2021

The relationship between body-mass index and overall survival in non-small cell lung cancer by sex, smoking status, and race: A pooled analysis of 20,937 International lung Cancer consortium (ILCCO) patients.

Lung Cancer 2021 02 4;152:58-65. Epub 2020 Dec 4.

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

Introduction: The relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC).

Methods: Data from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses.

Results: Among 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; p = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (p = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (p<0.001) and obese categories (p = 0.004) relative to the normal-BMI category, when compared to male ever-smokers.

Conclusion: Underweight and obese female ever-smokers were associated with worse outcomes in White-patients. These BMI associations were not observed in Asian-patients and never-smokers. Black-patients had more favorable outcomes in the extremes of BMI when compared to White-patients. Body composition in Black-patients, and NSCLC subtypes more commonly seen in Asian-patients and never-smokers, may account for differences in these BMI-OS relationships.
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http://dx.doi.org/10.1016/j.lungcan.2020.11.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042597PMC
February 2021

Role of social ecological model level on young Pacific children's sugar-sweetened beverage and water intakes: Children's Healthy Living intervention.

Public Health Nutr 2021 Jun 25;24(8):2318-2323. Epub 2020 Nov 25.

College of Tropical Agriculture and Human Resources, University of Hawai'i at Mānoa, Honolulu, HI96822, USA.

Objective: To examine children's sugar-sweetened beverage (SSB) and water intakes in relation to implemented intervention activities across the social ecological model (SEM) during a multilevel community trial.

Design: Children's Healthy Living was a multilevel, multicomponent community trial that reduced young child obesity (2013-2015). Baseline and 24-month cross-sectional data were analysed from nine intervention arm communities. Implemented intervention activities targeting reduced SSB and increased water consumption were coded by SEM level (child, caregiver, organisation, community and policy). Child SSB and water intakes were assessed by caregiver-completed 2-day dietary records. Multilevel linear regression models examined associations of changes in beverage intakes with activity frequencies at each SEM level.

Setting: US-Affiliated Pacific region.

Participants: Children aged 2-8 years (baseline: n 1343; 24 months: n 1158).

Results: On average (± sd), communities implemented 74 ± 39 SSB and 72 ± 40 water activities. More than 90 % of activities targeted both beverages together. Community-level activities (e.g. social marketing campaign) were most common (61 % of total activities), and child-level activities (e.g. sugar counting game) were least common (4 %). SSB activities across SEM levels were not associated with SSB intake changes. Additional community-level water activities were associated with increased water intake (0·62 ml/d/activity; 95 % CI: 0·09, 1·15) and water-for-SSB substitution (operationalised as SSB minus water: -0·88 ml/d/activity; 95 % CI: -1·72, -0·03). Activities implemented at the organization level (e.g. strengthening preschool wellness guidelines) and policy level (e.g. SSB tax advocacy) also suggested greater water-for-SSB substitution (P < 0·10).

Conclusions: Community-level intervention activities were associated with increased water intake, alone and relative to SSB intake, among young children in the Pacific region.
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http://dx.doi.org/10.1017/S1368980020004796DOI Listing
June 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
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