Publications by authors named "Veronica Wendy Setiawan"

80 Publications

Diet quality and all-cause and cancer-specific mortality in cancer survivors and non-cancer individuals: the Multiethnic Cohort Study.

Eur J Nutr 2021 Oct 17. Epub 2021 Oct 17.

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

Purpose: We examined post-diagnostic diet quality in relation to all-cause and cancer-specific mortality among adults diagnosed with invasive cancer between cohort entry (45-75 years) and their 10-year follow-up, in comparison with those without invasive cancer during that period, in the Multiethnic Cohort.

Methods: Data were from 70,045 African Americans, Native Hawaiians, Japanese Americans, Latinos, and Whites (6370 with cancer, 63,675 without cancer). Diet quality was measured by the Healthy Eating Index (HEI)-2015, the Alternative HEI-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and the Dietary Approaches to Stop Hypertension (DASH) scores, using a food frequency questionnaire. Multivariable Cox models estimated the association of the dietary indexes at 10-year follow-up and changes since baseline with subsequent mortality.

Results: Post-diagnostic scores from all four indexes were associated with lower mortality: for the highest vs. lowest quartiles, hazard ratio (HR) for all-cause mortality was 0.74 (95% CI 0.67-0.82) for HEI-2015, 0.82 (0.74-0.92) for AHEI-2010, 0.74 (0.66-0.84) for aMED, and 0.82 (0.74-0.91) for DASH. The corresponding HRs for cancer mortality were 0.84 (0.71-1.00), 0.85 (0.71-1.00), 0.71 (0.59-0.85), and 0.84 (0.71-1.00). Compared to stable scores over 10 years (< 0.5 SD change), HR for all-cause mortality was 0.87 (0.79-0.97) for ≥ 1 SD increase in HEI-2015 and was 1.22 to 1.29 for ≥ 1 SD decrease in scores across the four indexes. These HRs were similar to those for participants without cancer.

Conclusion: Post-diagnostic high-quality diet was related to lower all-cause and cancer mortality among adult cancer survivors, with risk reduction comparable to that among participants without cancer.
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http://dx.doi.org/10.1007/s00394-021-02700-2DOI Listing
October 2021

Association of Genetic Risk Score With NAFLD in An Ethnically Diverse Cohort.

Hepatol Commun 2021 10 18;5(10):1689-1703. Epub 2021 Jun 18.

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

Most genetic studies of nonalcoholic fatty liver disease (NAFLD) have been conducted in Whites. In this large and ethnically diverse cohort, we assessed the transportability of previously identified genetic variants for NAFLD, built a genetic risk score (GRS), and examined its association with NAFLD risk in multiple ethnic groups. Thirty previously identified genome-wide association studies (GWAS) variants (P < 5 × 10 ) and 17 other variants associated with NAFLD were examined in a nested case-control study of NAFLD (1,448 cases/8,444 controls) in this multi-ethnic cohort study. We then built a GRS using 11 independent single-nucleotide polymorphisms from these prior studies and examined its association with NAFLD by cirrhosis status across multiple ethnic groups. Of the 30 GWAS SNPs, 20 (67%) were replicated (P < 0.05) in the pooled multi-ethnic population. The highest percentage of replication was seen in Latinos (43%), followed by Japanese Americans (37%), Whites (17%), and Native Hawaiians and African Americans (≤10%). Several genetic variants, including those in PNPLA3 (patatin-like phospholipase domain containing 3), HSD17B13 (hydroxysteroid 17-beta dehydrogenase 13), TM6SF2 (transmembrane 6 superfamily member 2), GATAD2A (GATA zinc finger domain containing 2A), GCKR (glucokinase regulator), SUGP1 (SURP and G-patch domain containing 1), MBOAT7 (membrane bound O-acyltransferase domain containing 7), TRIB1 (tribbles pseudokinase 1), SAMM50 (sorting and assembly machinery component), and ERLIN1 (ER lipid raft associated 1)-CHUK (component of inhibitor of nuclear factor kappa B kinase complex)-CWF19L1 (CWF19 like cell cycle control factor 1) gene cluster, were replicated in at least two ethnic groups. An 11-SNP weighted GRS was associated with NAFLD risk in the multi-ethnic population (odds ratio [OR] per SD increase = 1.41; 95% confidence interval [CI] = 1.32-1.50), as well as in each ethnic group (OR ranged from 1.30 in African Americans to 1.52 in Latinos). The GRS-NAFLD association was stronger for NAFLD with cirrhosis (OR = 1.67; 95% CI = 1.46-1.92) compared to NAFLD without cirrhosis (OR = 1.37; 95% CI = 1.28-1.46) (P = 0.003). Conclusion: In this ethnically diverse cohort, we replicated several key genetic variants for NAFLD and showed the utility of GRS based on the risk alleles for NAFLD risk stratification in multiple ethnic groups.
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http://dx.doi.org/10.1002/hep4.1751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485887PMC
October 2021

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323875PMC
July 2021

Etiology and Outcomes of Hepatocellular Carcinoma in an Ethnically Diverse Population: The Multiethnic Cohort.

Cancers (Basel) 2021 Jul 12;13(14). Epub 2021 Jul 12.

Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA.

Backgrounds: HCC incidence varies by race/ethnicity. We characterized racial differences in underlying etiology, presentation, and survival in the linkage of Multiethnic Cohort Study with SEER and Medicare claims.

Methods: HCC characteristics, treatment, and underlying etiology in participants were obtained. Deaths were ascertained using state death certificates and the National Death Index. Risk factors were collected via questionnaires. Cox models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for death.

Results: Among 359 cases, the average age at diagnosis was 75.1. The most common etiology was hepatitis C (HCV) (33%), followed by nonalcoholic fatty liver disease (NAFLD) (31%), and different by ethnicity ( < 0.0001). African Americans (AA) (59.5%) and Latinos (40.6%) were more likely to be diagnosed with HCV-related HCC. In Japanese Americans (33.1%), Native Hawaiians (39.1%), and whites (34.8%), NAFLD was the most common etiology. Receipt of treatment varied across ethnic groups ( = 0.0005); AA had the highest proportion of no treatment (50.0%), followed by Latinos (45.3%), vs. whites (15.2%). HCC (72.2%) was the most common cause of death. In a multivariate analysis, AA (HR = 1.87; 95% CI: 1.06-3.28) had significantly higher mortality compared to whites.

Conclusions: We found significant ethnic differences in HCC underlying etiology, receipt of treatment, and outcome. The findings are important for reducing disparities.
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http://dx.doi.org/10.3390/cancers13143476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305188PMC
July 2021

The association between ambient air pollutants and pancreatic cancer in the Multiethnic Cohort Study.

Environ Res 2021 Jun 30;202:111608. Epub 2021 Jun 30.

Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA. Electronic address:

Background: Prior studies examining the association between ambient air pollutants and pancreatic cancer have been conducted in racially/ethnically homogeneous samples and have produced mixed results, with some studies supporting evidence of an association with fine particulate matter.

Methods: To further investigate these findings, we estimated exposure levels of particulate matter (PM, PM) and oxides of nitrogen (NO, and NO) using kriging interpolation for 100,527 men and women from the Multiethnic Cohort Study, residing largely in Los Angeles County from 1993 through 2013. We measured the association between these air pollutants and incident pancreatic cancer using Cox proportional hazards models with time-varying pollutant measures, with adjustment for confounding factors.

Results: A total of 821 incident pancreatic cancer and 1,660,488 person-years accumulated over the study period, with an average follow-up time of over 16 years. PM (per 10 μg/m) was associated with incident pancreatic cancer (hazard ratio [HR] = 1.61; 95% CI, 1.09, 2.37). This PM -association was strongest among Latinos (HR = 3.59; 95% CI, 1.60, 8.06) and ever smokers (HR = 1.76; 95% CI, 1.05, 2.94). There was no association for PM (HR = 1.12; 95% CI, 0.94, 1.32, per 10 μg/m), NO (HR = 1.14; 95% CI, 0.88, 1.48, per 50 ppb), or NO (HR = 1.14; 95% CI, 0.85, 1.54, per 20 ppb).

Conclusions: Our findings support prior research identifying an association between fine particulate matter, PM, and pancreatic cancer. Although not statistically heterogeneous, this association was most notable among Latinos and smokers. Future studies are needed to replicate these results in an urban setting and in a racially/ethnically diverse population.
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http://dx.doi.org/10.1016/j.envres.2021.111608DOI Listing
June 2021

Associations between Genetically Predicted Circulating Protein Concentrations and Endometrial Cancer Risk.

Cancers (Basel) 2021 Apr 26;13(9). Epub 2021 Apr 26.

Population Sciences in the Pacific Program, Cancer Epidemiology Division, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA.

Endometrial cancer (EC) is the leading female reproductive tract malignancy in developed countries. Currently, genome-wide association studies (GWAS) have identified 17 risk loci for EC. To identify novel EC-associated proteins, we used previously reported protein quantitative trait loci for 1434 plasma proteins as instruments to evaluate associations between genetically predicted circulating protein concentrations and EC risk. We studied 12,906 cases and 108,979 controls of European descent included in the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the UK Biobank. We observed associations between genetically predicted concentrations of nine proteins and EC risk at a false discovery rate of <0.05 (-values range from 1.14 × 10 to 3.04 × 10). Except for vascular cell adhesion protein 1, all other identified proteins were independent from known EC risk variants identified in EC GWAS. The respective odds ratios (95% confidence intervals) per one standard deviation increase in genetically predicted circulating protein concentrations were 1.21 (1.13, 1.30) for DNA repair protein RAD51 homolog 4, 1.27 (1.14, 1.42) for desmoglein-2, 1.14 (1.07, 1.22) for MHC class I polypeptide-related sequence B, 1.05 (1.02, 1.08) for histo-blood group ABO system transferase, 0.77 (0.68, 0.89) for intestinal-type alkaline phosphatase, 0.82 (0.74, 0.91) for carbohydrate sulfotransferase 15, 1.07 (1.03, 1.11) for D-glucuronyl C5-epimerase, and 1.07 (1.03, 1.10) for CD209 antigen. In conclusion, we identified nine potential EC-associated proteins. If validated by additional studies, our findings may contribute to understanding the pathogenesis of endometrial tumor development and identifying women at high risk of EC along with other EC risk factors and biomarkers.
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http://dx.doi.org/10.3390/cancers13092088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123478PMC
April 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

Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

Cancer Epidemiol Biomarkers Prev 2021 01 3;30(1):217-228. Epub 2020 Nov 3.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.

Methods: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data.

Results: Genetic correlation analysis revealed significant genetic correlation between the two cancers ( = 0.43, = 2.66 × 10). We found seven loci associated with risk for both cancers ( < 2.4 × 10). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified ( < 5 × 10). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation.

Conclusions: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.

Impact: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0739DOI Listing
January 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

Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk.

Cancer Epidemiol Biomarkers Prev 2020 12 23;29(12):2735-2739. Epub 2020 Sep 23.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Background: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome.

Methods: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data.

Results: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98-1.02; arachidonic acid OR = 1.00, 95% CI = 0.99-1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex.

Conclusions: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk.

Impact: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710600PMC
December 2020

Replication and Genetic Risk Score Analysis for Pancreatic Cancer in a Diverse Multiethnic Population.

Cancer Epidemiol Biomarkers Prev 2020 12 21;29(12):2686-2692. Epub 2020 Sep 21.

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

Background: Genome-wide association studies (GWAS) have identified several SNPs associated with pancreatic cancer. No studies yet have attempted to replicate these SNPs in US minority populations. We aimed to replicate the associations of 31 GWAS-identified SNPs with pancreatic cancer and build and test a polygenic risk score (PRS) for pancreatic cancer in an ethnically diverse population.

Methods: We evaluated 31 risk variants in the Multiethnic Cohort and the Southern Community Cohort Study. We included 691 pancreatic ductal adenocarcinoma (PDAC) cases and 13,778 controls from African-American, Japanese-American, Latino, Native Hawaiian, and white participants. We tested the association between each SNP and PDAC, established a PRS using the 31 SNPs, and tested the association between the score and PDAC risk.

Results: Eleven of the 31 SNPs were replicated in the multiethnic sample. The PRS was associated with PDAC risk [OR top vs. middle quintile = 2.25 (95% confidence interval, 1.73-2.92)]. Notably, the PRS was associated with PDAC risk in all ethnic groups except Native Hawaiian (OR per risk allele ranged from 1.33 in Native Hawaiians to 1.91 in African Americans; heterogeneity = 0.12).

Conclusions: This is the first study to replicate 11 of the 31 GWAS-identified risk variants for pancreatic cancer in multiethnic populations, including African Americans, Japanese Americans, and Latinos. Our results also suggest a potential utility of PRS with GWAS-identified risk variants for the identification of individuals at increased risk for PDAC across multiple ethnic groups.

Impact: PRS can potentially be used to stratify pancreatic cancer risk across multiple ethnic groups.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710597PMC
December 2020

Methylation of immune-regulatory cytokine genes and pancreatic cancer outcomes.

Epigenomics 2020 08 1;12(15):1273-1285. Epub 2020 Sep 1.

Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA 90095, USA.

Given the immunosuppressive nature of pancreatic cancer, we investigated the relationship between epigenetic modification of immune-regulatory cytokine genes and pancreatic cancer outcomes. We evaluated DNA methylation of 184 pancreatic tumor samples from The Cancer Genome Atlas for 111 CpG loci in seven cytokine genes: , , , , , and . We used Cox regression to evaluate the associations between methylation and overall survival, disease-specific survival and disease progression (α = 0.05). Poorer survival was associated with increased methylation in fifteen CpG probes in , , and . We also detected improved outcomes for three loci in , and . Epigenetic regulation of cytokine-related gene expression may be associated with pancreatic cancer outcomes.
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http://dx.doi.org/10.2217/epi-2019-0335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546161PMC
August 2020

Associations Between Reproductive and Hormone-Related Factors and Risk of Nonalcoholic Fatty Liver Disease in a Multiethnic Population.

Clin Gastroenterol Hepatol 2021 06 12;19(6):1258-1266.e1. Epub 2020 Aug 12.

Department of Preventive Medicine; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California. Electronic address:

Background & Aims: Despite apparent differences between men and women in the prevalence and incidence of nonalcoholic fatty liver disease (NAFLD), there are limited epidemiologic data regarding the associations of reproductive and hormone-related factors with NAFLD. We examined the associations of these factors and exogenous hormone use with NAFLD risk in African American, Japanese American, Latino, Native Hawaiian, and white women.

Methods: We conducted a nested case-control study (1861 cases and 17,664 controls) in the Multiethnic Cohort Study. NAFLD cases were identified using Medicare claims data; controls were selected among participants without liver disease and individually matched to cases by birth year, ethnicity, and length of Medicare enrollment. Reproductive and hormone-related factors and covariates were obtained from the baseline questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% CIs.

Results: Later age at menarche was associated inversely with NAFLD (P = .01). Parity, regardless of number of children or age at first birth, was associated with increased risk of NAFLD (OR, 1.25; 95% CI, 1.05-1.48). Oral contraceptive use also was linked to increased risk of NAFLD (OR, 1.14; 95% CI, 1.01-1.29; duration of use P = .04). Compared with women with natural menopause, those with oophorectomy (OR, 1.41; 95% CI, 1.18-1.68) or hysterectomy (OR, 1.33; 95% CI, 1.11-1.60) had an increased risk of NAFLD. A longer duration of menopause hormone therapy (only estrogen therapy) was linked with an increasing risk of NAFLD (OR per 5 years of use, 1.08, 95% CI, 1.01-1.15).

Conclusions: Findings from a large multiethnic study support the concept that menstrual and reproductive factors, as well as the use of exogenous hormones, are associated with the risk of NAFLD.
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http://dx.doi.org/10.1016/j.cgh.2020.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878579PMC
June 2021

MR elastography-based liver fibrosis correlates with liver events in nonalcoholic fatty liver patients: A multicenter study.

Liver Int 2020 09 22;40(9):2242-2251. Epub 2020 Jul 22.

Fatty Liver Program, Division of Digestive and Liver Diseases, Comprehensive Transplant Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Background & Aims: Liver fibrosis assessed by liver biopsy is predictive of clinical liver events in patients with nonalcoholic fatty liver disease (NAFLD). Magnetic resonance elastography (MRE) correlates with liver biopsy in assessing liver fibrosis. However, data assessing the relationship between MRE and clinical liver events are lacking. We investigated the association between MRE and clinical liver events/death and identified the cut-off to predict clinical liver events in NAFLD patients.

Methods: We conducted a multicenter retrospective study of NAFLD patients who underwent MRE between 2016 and 2019. Clinical liver events were defined as decompensation events and death. We categorized patients into noncirrhosis, compensated cirrhosis and decompensated cirrhosis. Fisher's exact test was used to test association strength. Receiver operative curve methods were used to determine the optimal cut-off of MRE liver stiffness and to maximize the accuracy for classifying noncirrhosis, compensated cirrhosis and decompensated cirrhosis. Logistic regression modelling was used to predict decompensation.

Results: The study included 320 NAFLD patients who underwent MRE. The best threshold for distinguishing cirrhosis from noncirrhosis was 4.39 kPa (AUROC 0.92) and from decompensated cirrhosis was 6.48 kPa (AUROC 0.71). Odds of decompensation increased as liver stiffness increased (OR 3.28) (P < .001). Increased liver stiffness was associated with ascites, hepatic encephalopathy, oesophageal variceal bleeding and mortality (median 7.10, 10.15 and 10.15 kPa respectively).

Conclusion: In NAFLD patients, liver stiffness measured by MRE with a cut-off of ≥6.48 kPa is associated with decompensation and mortality, and specific MRE cut-offs are predictive of individual clinical liver events.
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http://dx.doi.org/10.1111/liv.14593DOI Listing
September 2020

Population-specific reference panels are crucial for genetic analyses: an example of the CREBRF locus in Native Hawaiians.

Hum Mol Genet 2020 08;29(13):2275-2284

Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

Statistical imputation applied to genome-wide array data is the most cost-effective approach to complete the catalog of genetic variation in a study population. However, imputed genotypes in underrepresented populations incur greater inaccuracies due to ascertainment bias and a lack of representation among reference individuals, further contributing to the obstacles to study these populations. Here we examined the consequences due to the lack of representation by genotyping in a large number of self-reported Native Hawaiians (N = 3693) a functionally important, Polynesian-specific variant in the CREBRF gene, rs373863828. We found the derived allele was significantly associated with several adiposity traits with large effects (e.g. ~ 1.28 kg/m2 per allele in body mass index as the most significant; P = 7.5 × 10-5), consistent with the original findings in Samoans. Due to the current absence of Polynesian representation in publicly accessible reference sequences, rs373863828 or its proxies could not be tested through imputation using these existing resources. Moreover, the association signals at the entire CREBRF locus could not be captured by alternative approaches, such as admixture mapping. In contrast, highly accurate imputation can be achieved even if a small number (<200) of internally constructed Polynesian reference individuals were available; this would increase sample size and improve the statistical evidence of associations. Taken together, our results suggest the alarming possibility that lack of representation in reference panels could inhibit discovery of functionally important loci such as CREBRF. Yet, they could be easily detected and prioritized with improved representation of diverse populations in sequencing studies.
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http://dx.doi.org/10.1093/hmg/ddaa083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399533PMC
August 2020

Changes in Diet Quality over 10 Years Are Associated with Baseline Sociodemographic and Lifestyle Factors in the Multiethnic Cohort Study.

J Nutr 2020 07;150(7):1880-1888

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

Background: Trends in diet quality among US adults indicate a steady improvement, but data on longitudinal individual-level changes in diet quality are still limited.

Objective: We examined changes in diet quality over 10 y and sought to determine whether baseline sociodemographic and lifestyle factors predicted the changes in a multiethnic population.

Methods: Data were from 63,255 African American, Native Hawaiian, Japanese American, Latino, and white men and women (45-75 y old at baseline) in the Multiethnic Cohort, who completed a quantitative food frequency questionnaire at baseline (1993-1996) and 10-y follow-up (2003-2007) and had no prevalent cancer or heart disease at either survey. Overall diet quality was measured by use of the Healthy Eating Index-2015 (HEI-2015), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet score, and the Dietary Approaches to Stop Hypertension (DASH) score. We used a general linear model with adjustment for covariates to compare diet quality changes by baseline characteristics in men and women separately.

Results: Overall diet quality improved over 10 y by 3.2 points in men and 2.9 in women assessed using the HEI-2015, although scores for some components worsened (saturated and trans fats, indicating increased intake) or remained unchanged at a low quality level (whole grains, dairy, and sodium). In multivariable models where changes in HEI-2015, AHEI-2010, and DASH were harmonized to a 100-point score, greater increases in scores in both men and women were found for Japanese American ethnicity (increase by 0.5-4.7 in the 3 scores, P < 0.03), higher education (by 0.5-1.5, P ≤ 0.001), normal weight (BMI 18.5 to <25, by 0.6-2.5, P ≤ 0.01), nonsmoking (by 1.5-2.7, P < 0.001), higher moderate/vigorous physical activity level (by 0.3-0.8, P ≤ 0.04), and multivitamin use (by 0.4-0.7, P < 0.001) at baseline.

Conclusions: Sociodemographic and lifestyle factors, closely associated with diet quality, also predicted subsequent changes in diet quality over time in this multiethnic population.
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http://dx.doi.org/10.1093/jn/nxaa102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330479PMC
July 2020

New-Onset Diabetes, Longitudinal Trends in Metabolic Markers, and Risk of Pancreatic Cancer in a Heterogeneous Population.

Clin Gastroenterol Hepatol 2020 07 4;18(8):1812-1821.e7. Epub 2019 Dec 4.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Norris Comprehensive Cancer Center, Los Angeles, California.

Background & Aims: Observational studies of predominantly white populations have found new-onset diabetes to be associated with increased risk of pancreatic cancer. We sought to determine whether this relationship applies to other races or ethnicities and to identify metabolic profiles associated with increased risk of pancreatic cancer.

Methods: We conducted a population-based cohort study of Asian, black, Hispanic and white patients from Kaiser Permanente Southern California from 2006 through 2016 (n = 1,499,627). Patients with diabetes were identified based on glucose and hemoglobin A1c (HbA1c) measurements. We used Cox regression to assess the relationship between diabetes status and duration and pancreatic cancer. For patients with recent diagnoses of diabetes (1 year or less) we compared longitudinal changes in glucose, HbA1c, and weight, from time of diabetes diagnosis through 3 years prior to the diagnosis, in patients with vs without pancreatic cancer.

Results: We identified 2,002 incident cases of pancreatic cancer from nearly 7.5 million person-years of follow-up. Compared to patients without diabetes, individuals who received a recent diagnosis of diabetes had an almost 7-fold increase in risk of pancreatic cancer (relative risk, 6.91; 95% CI, 5.76-8.30). Among patients with a recent diagnosis of diabetes, those who developed pancreatic cancer had more rapid increases in levels of glucose (Δslope: cases, 37.47 mg/dL vs non-cases, 27.68 mg/dL) and HbA1c (Δslope: cases, 1.39% vs non-cases, 0.86%) in the month preceding the diagnosis of diabetes, and subtle weight loss in the prior years (slope: cases -0.18 kg/interval vs non-cases 0.33 kg/interval). These longitudinal changes in markers of metabolism were stronger for specific race and ethnic groups.

Conclusions: In a study of a large ethnically diverse population, we found risk of pancreatic cancer to be increased among patients with a diagnosis of diabetes in the past year among different races and ethnicities. Weight loss and rapid development of poor glycemic control were associated with increased risk of pancreatic cancer in multiple races.
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http://dx.doi.org/10.1016/j.cgh.2019.11.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269863PMC
July 2020

Diet Associations With Nonalcoholic Fatty Liver Disease in an Ethnically Diverse Population: The Multiethnic Cohort.

Hepatology 2020 06 14;71(6):1940-1952. Epub 2020 Feb 14.

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

Background And Aims: Epidemiological data on dietary risk factors for nonalcoholic fatty liver disease (NAFLD) from population-based studies, particularly in an ethnically diverse population, are scarce. We examined dietary factors in relation to NAFLD risk in African Americans, Japanese Americans, Latinos, native Hawaiians, and whites in the Multiethnic Cohort (MEC).

Approach And Results: A nested case-control analysis was conducted within the MEC, a large prospective study with >215,000 older adult participants in Hawaii and California. NAFLD was identified using Medicare claims data, and controls were selected among participants without liver disease and individually matched to cases by birth year, sex, ethnicity, and length of Medicare enrollment. Diet was assessed at baseline through a validated quantitative food frequency questionnaire. Diet-NAFLD associations were quantified by odds ratios and 95% confidence intervals using multivariable conditional logistic regression. The study consisted of 2,974 NAFLD cases (518 with cirrhosis, 2,456 without cirrhosis) and 29,474 matched controls. Red meat (P trend = 0.010), processed red meat (P trend = 0.004), poultry (P trend = 0.005), and cholesterol (P trend = 0.005) intakes were positively associated with NAFLD, while dietary fiber intake (P trend = 0.003) was inversely associated with risk. Stronger associations were observed between red meat and cholesterol and NAFLD with cirrhosis than without cirrhosis (P heterogeneity ≤0.014).

Conclusions: Dietary factors are independently associated with NAFLD and NAFLD-related cirrhosis in a multiethnic population. Decreasing the consumption of cholesterol, red and processed meat, and poultry and increasing consumption of fiber may reduce the risk for NAFLD and related advanced liver disease.
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http://dx.doi.org/10.1002/hep.30967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093243PMC
June 2020

Identification of novel epithelial ovarian cancer loci in women of African ancestry.

Int J Cancer 2020 06 8;146(11):2987-2998. Epub 2019 Oct 8.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC.

Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome-wide association study in African ancestry women with 755 EOC cases, including 537 high-grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (p < 1 × 10 ), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs4286604 (12 kb 3' of UGT2A2) and rs142091544 (5 kb 5' of WWC1). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5' of follistatin [FST]), rs57403204 (81 kb 3' of MAGEC1), rs79079890 (LOC105376360 intronic), rs66459581 (5 kb 5' of PRPSAP1), rs116046250 (GABRG3 intronic) and rs192876988 (32 kb 3' of GK2). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary (AKR1C3 and FST), and two are linked to cancer (AKR1C3 and MAGEC1). In follow-up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women (p = 0.002), increased risk of ER positive breast cancer in African ancestry women (p = 0.027) and decreased expression of GK2 in HGSOC tissue from African ancestry women (p = 0.004). A European ancestry-derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry.
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http://dx.doi.org/10.1002/ijc.32653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523187PMC
June 2020

Ovarian Cancer in Women of African Ancestry (OCWAA) consortium: a resource of harmonized data from eight epidemiologic studies of African American and white women.

Cancer Causes Control 2019 Sep 24;30(9):967-978. Epub 2019 Jun 24.

Slone Epidemiology Center, Boston University, Boston, MA, USA.

Purpose: Although the incidence rate of epithelial ovarian cancer (EOC) is somewhat lower in African American (AA) than white women, survival is worse. The Ovarian Cancer in Women of African Ancestry (OCWAA) consortium will overcome small, study-specific sample sizes to better understand racial differences in EOC risk and outcomes.

Methods: We harmonized risk factors and prognostic characteristics from eight U.S.

Studies: the North Carolina Ovarian Cancer Study (NCOCS), the Los Angeles County Ovarian Cancer Study (LACOCS), the African American Cancer Epidemiology Study (AACES), the Cook County Case-Control Study (CCCCS), the Black Women's Health Study (BWHS), the Women's Health Initiative (WHI), the Multiethnic Cohort Study (MEC), and the Southern Community Cohort Study (SCCS).

Results: Determinants of disparities for risk and survival in 1,146 AA EOC cases and 2,922 AA controls will be compared to 3,368 white EOC cases and 10,270 white controls. Analyses include estimation of population-attributable risk percent (PAR%) by race.

Conclusion: OCWAA is uniquely positioned to study the epidemiology of EOC in AA women compared with white women to address disparities. Studies of EOC have been underpowered to address factors that may explain AA-white differences in the incidence and survival. OCWAA promises to provide novel insight into disparities in ovarian cancer.
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http://dx.doi.org/10.1007/s10552-019-01199-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325484PMC
September 2019

Differences in Pancreatic Cancer Incidence Rates and Temporal Trends Across Asian Subpopulations in California (1988-2015).

Pancreas 2019 08;48(7):931-933

Objective: Ethnic disparities in pancreatic cancer (PanCan) incidence exist, but little is known about incidence trends in heterogeneous Asian Americans. We examined PanCan incidence and temporal patterns among detailed ethnic populations, including Asian American subgroups.

Methods: A total of 71,099 invasive exocrine PanCan cases were identified using the California Cancer Registry between 1988 and 2015. Cases were grouped into mutually exclusive groups of non-Hispanic (NH) white, NH black, Hispanic, NH Asian/Pacific Islander (API), and NH American Indian/Alaska Native (AIAN). Asians were further identified by specific ethnicity.

Results: The age-adjusted incidence rates (AAIRs, per 100,000) of PanCan varied significantly across racial/ethnic groups, ranging from the highest of 10.4 in NH blacks to 7.6 in NH whites, 7.1 in Hispanics, 6.2 in NH APIs, and to the lowest of 5.2 in NH AIAN. Despite the relatively low rate in the NH APIs, the rates across Asian subgroups varied significantly, with rates similar to NH whites in Japanese (8.1) and Koreans (7.5) to the low rate in South Asians (4.4).

Conclusions: Significant heterogeneity of PanCan incidence in disaggregated Asian Americans is a novel finding. These results fill a gap regarding PanCan burden in Asian Americans and underscore the importance of disaggregating ethnic populations in cancer research.
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http://dx.doi.org/10.1097/MPA.0000000000001337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629494PMC
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

Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women.

Cancer Med 2019 05 18;8(5):2503-2513. Epub 2019 Apr 18.

Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.
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http://dx.doi.org/10.1002/cam4.1996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536963PMC
May 2019

High-Quality Diets Are Associated With Reduced Risk of Hepatocellular Carcinoma and Chronic Liver Disease: The Multiethnic Cohort.

Hepatol Commun 2019 Mar 31;3(3):437-447. Epub 2019 Jan 31.

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

Hepatocellular carcinoma (HCC) and chronic liver disease (CLD) are major sources of morbidity and mortality globally. Both HCC incidence and CLD mortality are known to vary by race. There is limited research on the association between dietary measures and these outcomes in a diverse population. We prospectively investigated the associations between four diet quality index (DQI) scores (Healthy Eating Index-2010, Alternative Healthy Eating Index-2010, Alternate Mediterranean Diet [aMED], and Dietary Approaches to Stop Hypertension), HCC incidence, and CLD mortality in the Multiethnic Cohort. We analyzed data from 169,806 African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites, aged 45 to 75 years. DQI scores were calculated by using a validated food frequency questionnaire administered at baseline. During an average 17 years of follow-up, 603 incident cases of HCC and 753 CLD deaths were identified among study participants. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for each DQI were estimated using Cox regression. Higher aMED scores, reflecting favorable adherence to a healthful diet, were associated with a lower risk of HCC (quintile [Q]5 versus Q1 HR, 0.68; 95% CI, 0.51-0.90; trend, = 0.02). In racial/ethnic-specific analyses, there was no significant heterogeneity across groups (interaction, = 0.32); however, the association only remained statistically significant among Latinos (Q4 versus Q1 HR, 0.47; 95% CI, 0.29-0.79; trend, = 0.006). All DQI measures were inversely associated with CLD mortality, with no significant heterogeneity by race/ethnicity. Higher aMED scores were associated with a lower risk of HCC. A higher score of any DQI was associated with a lower risk of CLD mortality. These results suggest that better diet quality may reduce HCC incidence and CLD mortality.
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http://dx.doi.org/10.1002/hep4.1313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396362PMC
March 2019

Body mass index, comorbidities, and hormonal factors in relation to meningioma in an ethnically diverse population: the Multiethnic Cohort.

Neuro Oncol 2019 03;21(4):498-507

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

Background: Meningioma is the most common intracranial tumor in the US and its etiology remains poorly understood. Meningioma has been predominantly studied among white populations. The aim of this study was to evaluate the associations of anthropometric, comorbidity, and hormonal factors with meningioma in an ethnically diverse population.

Methods: A nested case-control analysis was performed within the Multiethnic Cohort (MEC). Meningioma cases were identified via linkage with Medicare and the California Office of Statewide Health Planning and Development Hospital Discharge data and were matched to up to 10 controls. Anthropometric, comorbidities, physical activity level, and hormonal factors at baseline based on questionnaires were evaluated for association with meningioma.

Results: A total of 894 cases and 8918 matched controls were included in this study. Increasing body mass index (BMI) (P-trend = 0.041) and weight increases since age 21 (P-trend = 0.0052) were positively associated with meningioma. Hormonal factors including oral contraceptive use (odds ratio [OR]: 1.24; 95% CI: 1.01-1.51) and estrogen hormonal therapy use (per 5 years, OR: 1.07; 95% CI: 1.01-1.15) were associated with meningioma risk. Hypertension was positively associated with meningioma (OR: 1.26; 95% CI: 1.09-1.47), with individuals who reported a history of both hypertension and diabetes showing a stronger association (OR: 1.54; 95% CI: 1.17-2.03). The tests for heterogeneity across race/ethnicity were not statistically significant (P heterogeneity ≥ 0.17); however, the association of BMI with meningioma was mainly observed in Japanese Americans (P-trend = 0.0036) and hypertension in Japanese Americans (OR: 1.63; 95% CI: 1.17-2.27) and Native Hawaiians (OR: 1.86; 95% CI: 1.02-3.40).

Conclusion: Obesity, hormonal factors, and hypertension were associated with meningioma in an ethnically diverse population.
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http://dx.doi.org/10.1093/neuonc/noz005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422634PMC
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

The influence of neighborhood socioeconomic status and ethnic enclave on endometrial cancer mortality among Hispanics and Asian Americans/Pacific Islanders in California.

Cancer Causes Control 2018 Sep 28;29(9):875-881. Epub 2018 Jul 28.

Greater Bay Area Cancer Registry, Cancer Prevention Institute of California, 2201 Walnut Ave, Suite 300, Fremont, CA, 94538, USA.

Purpose: We investigated the role of neighborhood socioeconomic status (nSES) and residence in ethnic enclaves on mortality following endometrial cancer (EC) diagnosis among Hispanics and Asian Americans/Pacific Islanders (AAPI).

Methods: Using California Cancer Registry data, enhanced with census block group information on ethnic enclave and nSES, we examined 9,367 Hispanics and 5,878 AAPIs diagnosed with EC from 1988 to 2011. Cox proportional hazard models were used to estimate associations between all-cause and EC-specific mortality with nSES and ethnic enclaves, adjusting for subject sociodemographic and tumor characteristics.

Results: Hispanics in the lowest SES neighborhoods had a 39% and 36% increased risk of all-cause and EC-specific mortality, respectively, compared to Hispanics in the highest SES neighborhoods. AAPIs in the lowest SES neighborhoods had a 37% increased risk of all-cause mortality compared to AAPIs in the highest SES neighborhoods. Living in an ethnic enclave was associated with lower all-cause mortality risk for AAPIs.

Conclusions: Mortality risk varied by nSES and ethnic enclave among Hispanics and AAPIs. Women living in lower SES communities experienced significantly higher risk, highlighting the need to identify the specific neighborhood factors underlying these associations so that community-based interventions may be properly targeted.
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http://dx.doi.org/10.1007/s10552-018-1063-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466936PMC
September 2018

Pancreatic Cancer Related Health Disparities: A Commentary.

Cancers (Basel) 2018 Jul 18;10(7). Epub 2018 Jul 18.

Department of Biobehavioral Nursing Science, College of Nursing, University of Florida, Gainesville, FL 32610, USA.

We summarize the risk factors that may significantly contribute to racial disparities in pancreatic cancer, which is now the third leading cause of cancer deaths and projected to be second around 2030 in 12 years. For decades, the incidence rate of pancreatic cancer among Blacks has been 30% to 70% higher than other racial groups in the United States and the 5-year survival rate is approximately 5%. Diabetes and obesity have been identified as potentially predisposing factors to pancreatic cancer and both are more common among Blacks. Smoking continues to be one of the most important risk factors for pancreatic cancer and smoking rates are higher among Blacks compared to other racial groups. The overall risk of pancreatic cancer due to changes in DNA is thought to be the same for most racial groups; however, DNA methylation levels have been observed to be significantly different between Blacks and Whites. This finding may underlie the racial disparities in pancreatic cancer. Identification and prevention of these factors may be effective strategies to reduce the high incidence and mortality rates for pancreatic cancer among Blacks.
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http://dx.doi.org/10.3390/cancers10070235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070801PMC
July 2018

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

NASH Leading Cause of Liver Transplant in Women: Updated Analysis of Indications For Liver Transplant and Ethnic and Gender Variances.

Am J Gastroenterol 2018 11 8;113(11):1649-1659. Epub 2018 Jun 8.

Fatty Liver Program, Division of Digestive and Liver Diseases, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Biostatistics & Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Department of Surgery, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Texas Liver Institute, San Antonio, TX, USA. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. These authors contributed equally: Mazen Noureddin, Aarshi Vipani.

Objectives: Chronic infection with hepatitis C virus (HCV) was previously the leading indication for liver transplant (LT) in the United States. However, since 2014 the use of direct-acting antivirals (DAAs) has decreased the chronic HCV burden, while the prevalence of nonalcoholic steatohepatitis (NASH) has risen substantially through the last decade. Both gender and ethnic disparities in indications for LT have been shown in the past but no data on this have been reported since the implementation of DAAs.

Methods: We assessed changes in etiologies for LT listing and in gender and ethnic differences in those listed for LT. Adult patients registered for LT in the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between January 1, 2004 and December 31, 2016 were included. Multinomial logistic regression modeling was used to test for changes in waitlist or liver transplant rates.

Results: The study included 127,164 adult patients registered for LT. By 2016, alcoholic liver disease (ALD) was the leading etiology for waitlisting and LT; NASH was second; hepatocellular carcinoma (HCC) due to chronic HCV and chronic HCV alone were 3rd and 4th. NASH was the leading cause for LT for women and the 2nd leading cause for men (following ALD). NASH increased as the cause in all ethnic subgroups and was the leading cause in 2016 among Asian, Hispanic, and non-Hispanic white females. We also found that although the indication for liver transplant for hepatocellular carcinoma (HCC) due to HCV has increased over the years, this indication decreased for the first time between 2015 and 2016 in both males and females.

Conclusions: NASH is currently the second leading cause for LT waitlist registration/liver transplantation overall, and in females, the leading cause. Given the rate of increase, NASH will likely rise to become the leading indication for LT in males as well.
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http://dx.doi.org/10.1038/s41395-018-0088-6DOI Listing
November 2018
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