Circulating microRNAs in association with pancreatic cancer risk within 5 years.

Early detection is critical for improving pancreatic cancer prognosis. Our study aims to identify circulating microRNAs (miRNAs) associated with pancreatic cancer risk. The two-stage study used plasma samples collected ≤5 years prior to cancer diagnosis, from case-control studies nested in five prospective cohort studies. The discovery stage included 185 case-control pairs from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Replication stage samples comprised 277 pairs from Shanghai Women's Health Study/Shanghai Men's Health Study, Southern Community Cohort Study, and Multiethnic Cohort Study. Seven hundred and ninety-eight miRNAs were measured using the NanoString nCounter Analysis System. Odds ratios (OR) and 95% confidence intervals (CI) for per 10% change in miRNAs in association with pancreatic cancer risk were derived from conditional logistic regression analysis in discovery and replication studies, separately, and then meta-analyzed. Stratified analysis was conducted by age at diagnosis (<65/≥65 years) and time interval between sample collection and diagnosis (≤2/>2 years). In the discovery stage, 120 risk associated miRNAs were identified at p < .05. Three were validated in the replication stage: hsa-miR-199a-3p/hsa-miR-199b-3p, hsa-miR-767-5p, and hsa-miR-191-5p, with respective ORs (95% CI) being 0.89 (0.84-0.95), 1.08 (1.02-1.13), and 0.90 (0.85-0.95). Five additional miRNAs, hsa-miR-640, hsa-miR-874-5p, hsa-miR-1299, hsa-miR-22-3p, and hsa-miR-449b-5p, were validated among patients diagnosed at ≥65 years, with OR (95% CI) of 1.23 (1.09-1.39), 1.33 (1.16-1.52), 1.25 (1.09-1.43), 1.28 (1.12-1.46), 0.76 (0.65-0.89), and 1.22 (1.07-1.39), respectively. The miRNA targets were enriched in pancreatic carcinogenesis/progression-related pathways. Our study suggests that circulating miRNAs may identify individuals at high risk for pancreatic cancer ≤5 years prior to diagnosis, indicating its potential utility in cancer screening and surveillance.

Increasing risk of hepatocellular carcinoma with successive generations in the United States among Mexican American adults: The Multiethnic Cohort.

BACKGROUND: US-born Latinos have a higher incidence of hepatocellular carcinoma (HCC) than foreign-born Latinos. Acculturation to unhealthy lifestyle behaviors and an immigrant self-selection effect may play a role. In this study, the authors examined the influence of generational status on HCC risk among Mexican American adults. METHODS: The analytic cohort included 31,377 self-reported Mexican Americans from the Multiethnic Cohort Study (MEC). Generational status was categorized as: first-generation (Mexico-born; n = 13,382), second-generation (US-born with one or two parents born in Mexico; n = 13,081), or third-generation (US-born with both parents born in the United States; n = 4914). Multivariable Cox proportional hazards regression was performed to examine the association between generational status and HCC incidence. RESULTS: In total, 213 incident HCC cases were identified during an average follow-up of 19.5 years. After adjusting for lifestyle and neighborhood-level risk factors, second-generation and third-generation Mexican Americans had a 37% (hazard ratio [HR], 1.37; 95% confidence interval [CI], 0.98-1.92) and 66% (HR, 1.66; 95% CI, 1.11-2.49) increased risk of HCC, respectively, compared with first-generation Mexican Americans (p for trend = 0.012). The increased risk associated with generational status was mainly observed in males (second-generation vs. first-generation: HR, 1.60 [95% CI, 1.05-2.44]; third-generation vs. first-generation: HR, 2.08 [95% CI, 1.29-3.37]). CONCLUSIONS: Increasing generational status of Mexican Americans is associated with a higher risk of HCC. Further studies are needed to identify factors that contribute to this increased risk.

Excess pancreatic cancer risk due to smoking and modifying effect of quitting smoking: The Multiethnic Cohort Study.

PURPOSE: Risk factors for pancreatic cancer include racial/ethnic disparities and smoking. However, risk trajectories by smoking history and race/ethnicity are unknown. We examined the association of smoking with pancreatic cancer by race/ethnicity to generate age-specific incidence estimates by smoking history. METHODS: We modeled pancreatic cancer incidence by race/ethnicity, age, pack-years, and years-quit using an excess relative risk model for 182,011 Multiethnic Cohort participants. We tested heterogeneity of smoking variables and pancreatic cancer by race/ethnicity and predicted incidence by smoking history. RESULTS: We identified 1,831 incident pancreatic cancer cases over an average 19.3 years of follow-up. Associations of pack-years (p interaction by race/ethnicity = 0.41) and years-quit (p interaction = 0.83) with pancreatic cancer did not differ by race/ethnicity. Fifty pack-years smoked was associated with 91% increased risk (95% CI 54%, 127%) relative to never smokers in the combined sample. Every year quit corresponded to 9% decreased excess risk (95% CI 2%, 15%) from pack-years smoked. Differences in baseline pancreatic cancer risk across racial/ethnic groups (p < 0.001) translated to large differences in risk for smokers at older ages across racial/ethnic groups (65-122 cases per 100,000 at age 70). CONCLUSION: Smoking pack-years were positively associated with elevated pancreatic cancer risk. Predicted risk trajectories showed a high impact of smoking cessation at < 65 years. Although we did not identify significant heterogeneity in the association of pack-years or years quit with pancreatic cancer risk, current smoker risk varied greatly by race/ethnicity in later life due to large differences in baseline risk.

Global burden of liver cancer in males and females: Changing etiological basis and the growing contribution of NASH.

BACKGROUND AND AIM: The etiology of liver diseases has changed in recent years, but its impact on the comparative burden of liver cancer between males and females is unclear. We estimated sex differences in the burden of liver cancer across 204 countries and territories from 2010 to 2019. APPROACH AND RESULT: We analyzed temporal trends in the burden of liver cancer using the methodology framework of the 2019 Global Burden of Disease study. We estimated annual frequencies and age-standardized rates (ASRs) of liver cancer incidence, death, and disability-adjusted life-years (DALYs) by sex, country, region, and etiology of liver disease. Globally in 2019, the frequency of incident cases, deaths, and DALYs due to liver cancer were 376,483, 333,672, and 9,048,723 in males, versus 157,881, 150,904, and 3,479,699 in females. From 2010 to 2019, the incidence ASRs in males increased while death and DALY ASRs remained stable; incidence, death, and DALY ASRs in females decreased. Death ASRs for both sexes increased only in the Americas and remained stable or declined in remaining regions. In 2019, hepatitis B was the leading cause of liver cancer death in males, and hepatitis C in females. From 2010 to 2019, NASH had the fastest growing death ASRs in males and females. The ratio of female-to-male death ASRs in 2019 was lowest in hepatitis B (0.2) and highest in NASH (0.9). CONCLUSIONS: The overall burden of liver cancer is higher in males, although incidence and death ASRs from NASH-associated liver cancer in females approach that of males.

The EAT-Lancet Diet Index Is Associated with Lower Obesity and Incidence of Type 2 Diabetes in the Multiethnic Cohort.

BACKGROUND: The EAT-Lancet Commission has developed dietary recommendations, named the EAT-Lancet diet, to promote healthy nutrition and sustainable food production worldwide. OBJECTIVES: We developed an adapted score for the EAT-Lancet diet for participants of the Multiethnic Cohort (MEC) Study and its relation with incidence of obesity and type 2 diabetes (T2D). METHODS: The MEC includes 5 ethnic groups followed since 1993-1996. Anthropometric characteristics and dietary intake were assessed by questionnaire at cohort entry (Qx1) and 10 y later (Qx3). To create the EAT-Lancet index (range: 0-48 points), a 3-point scoring system for 16 food groups standardized to 2500 kcal/d was applied. T2D cases were identified through repeated self-reports and administrative data. In a prospective design, obesity at Qx3 and T2D incidence were evaluated using Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) while adjusting for relevant covariates. RESULTS: Among 193,379 MEC participants, the overall mean of the EAT-Lancet index score was 25 ± 4 points and 46,140 new T2D cases were identified. Higher adjusted means were observed in females than males, in participants of Japanese American and Native Hawaiian ancestry, and in those with healthy weight than overweight or obese. Obesity was lower in cohort members with higher EAT-Lancet scores (HR: 0.76; 95% CI: 0.73, 0.79 for tertile 3 compared with 1). Although T2D incidence was 10% lower among participants in the highest (27-42 points) compared with the lowest (9-23 points) EAT-Lancet index tertile (HR: 0.90; 95% CI: 0.88, 0.92), the association was attenuated after BMI adjustment (HR: 0.97; 95% CI: 0.94, 0.99). This inverse association with T2D was restricted to African American and European American participants. CONCLUSIONS: These findings support the hypothesis that adherence to the EAT-Lancet diet is related to a lower risk of obesity, which may be partially responsible for the small reduction in T2D incidence.

Smoking and pancreatic cancer: a sex-specific analysis in the Multiethnic Cohort study.

PURPOSE: To examine whether the detrimental smoking-related association with pancreatic cancer (PC) is the same for women as for men. METHODS: We analyzed data from 192,035 participants aged 45-75 years, enrolled in the Multiethnic Cohort study (MEC) in 1993-1996. We identified PC cases via linkage to the Hawaii and California Surveillance, Epidemiology, and End Results Program cancer registries through December 2017. RESULTS: During a mean follow-up of 19.2 years, we identified 1,936 incident PC cases. Women smokers smoked on average less than men smokers. In multivariate Cox regression models, as compared with sex-specific never smokers, current smokers had a similar elevated risk of PC for women, hazard ratio (HR) 1.49 (95% CI 1.24, 1.79) and as for men, HR 1.48 (95% CI 1.22, 1.79) (pheterogeneity: 0.79). Former smokers showed a decrease in risk of PC for men within 5 years, HR 0.74 (95% CI 0.57, 0.97) and for women within 10 years after quitting, HR 0.70 (95% CI 0.50, 0.96), compared with their sex-specific current smokers. Both sexes showed a consistent, strong, positive dose-response association with PC for the four measures (age at initiation, duration, number of cigarettes per day, number of pack-years) of smoking exposure among current smokers and an inverse association for years of quitting and age at smoking cessation among former smokers (all ptrend's < 0.001). CONCLUSION: Although MEC women smoke on average less than their men counterparts, the smoking-related increase in PC risk and the benefits of cessation seem to be of similar magnitudes for women as for men.

Risk factors for endometrial cancer in Black women.

PURPOSE: The incidence of endometrial cancer (EC) has been increasing faster among Black women than among other racial/ethnic groups in the United States. Although the mortality rate is nearly twice as high among Black than White women, there is a paucity of literature on risk factors for EC among Black women, particularly regarding menopausal hormone use and severe obesity. METHODS: We pooled questionnaire data on 811 EC cases and 3,124 controls from eight studies with data on self-identified Black women (4 case-control and 4 cohort studies). We analyzed cohort studies as nested case-control studies with up to 4 controls selected per case. We used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We observed a positive association between BMI and EC incidence (Ptrend < 0.0001) The OR comparing BMI ≥ 40 vs. < 25 kg/m2 was 3.92 (95% CI 2.91, 5.27). Abdominal obesity among those with BMI < 30 kg/m2 was not appreciably associated with EC risk (OR 1.21, 95% CI 0.74, 1.99). Associations of reproductive history with EC were similar to those observed in studies of White women. Long-term use of estrogen-only menopausal hormones was associated with an increased risk of EC (≥ 5 years vs. never use: OR 2.08, 95% CI: 1.06, 4.06). CONCLUSIONS: Our results suggest that the associations of established risk factors with EC are similar between Black and White women. Other explanations, such as differences in the prevalence of known risk factors or previously unidentified risk factors likely underlie the recent increases in EC incidence among Black women.

Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Modifying effects of race and ethnicity and APOE on the association of physical activity with risk of Alzheimer's disease and related dementias.

INTRODUCTION: We investigated whether the protective association of physical activity with risk of Alzheimer's disease and related dementias (ADRD) has genetic or behavioral variations. METHODS: In the Multiethnic Cohort, we analyzed moderate or vigorous physical activity (MVPA) reported at ages 45 to 75 among 88,047 participants in relation to 13,039 incident diagnoses of late-onset ADRD identified in Medicare claims (1999 to 2014), by five racial and ethnic groups, hours sitting, and in a subset (16%), apolipoprotein E (APOE) genotype. RESULTS: MVPA was inversely associated with ADRD (hazard ratio for ≥14 vs <2.5 hours/week: 0.83, 95% confidence interval [CI]: 0.76 to 0.90 in men; 0.88, 5% CI: 0.81 to 0.95 in women). The association was inverse in all racial and ethnic groups except Black participants (P-heterogeneity = 0.52), but stronger in individuals with lower levels of sitting duration or those who do not carry the APOE e4 risk allele. DISCUSSION: The different effects of physical activity by sitting duration and APOE genotype warrant further research.

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

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.

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

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.

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

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 (RRQ4vsQ1 1.18, 95% CI 1.02-1.37) and with borderline statistical significance in the SCCS (RRQ4vsQ1 1.31, 95% CI 0.93-1.86). This association was significant in African Americans (RRQ4vsQ1 1.49, 95% CI 1.06-2.11) and Latinos (RRQ4vsQ1 1.44, 95% CI 1.02-2.04) in the MEC, and among African Americans (RRQ4vsQ1 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 (pinteraction = 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.

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

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 (Ptrend = .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 Ptrend = .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.

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

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.

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

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 (PM2.5, PM10) and oxides of nitrogen (NOX, and NO2) 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. PM2.5 (per 10 µg/m3) was associated with incident pancreatic cancer (hazard ratio [HR] = 1.61; 95% CI, 1.09, 2.37). This PM2.5 -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 PM10 (HR = 1.12; 95% CI, 0.94, 1.32, per 10 µg/m3), NOx (HR = 1.14; 95% CI, 0.88, 1.48, per 50 ppb), or NO2 (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, PM2.5, 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.

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

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 × 10-6 ), 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.

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

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.

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

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.

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

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.

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

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.