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1.
PLoS Genet ; 17(2): e1009273, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33571193

RESUMO

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

2.
Br J Nutr ; : 1-9, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33441193

RESUMO

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

4.
Nat Genet ; 53(1): 65-75, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33398198

RESUMO

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


Assuntos
Grupos de Populações Continentais/genética , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias da Próstata/genética , Humanos , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Invasividade Neoplásica , Razão de Chances , Neoplasias da Próstata/diagnóstico , Fatores de Risco
5.
Lung Cancer ; 152: 58-65, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33352384

RESUMO

INTRODUCTION: The relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC). METHODS: Data from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses. RESULTS: Among 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; pinteraction = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (pinteraction = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (pinteraction<0.001) and obese categories (pinteraction = 0.004) relative to the normal-BMI category, when compared to male ever-smokers. CONCLUSION: Underweight and obese female ever-smokers were associated with worse outcomes in White-patients. These BMI associations were not observed in Asian-patients and never-smokers. Black-patients had more favorable outcomes in the extremes of BMI when compared to White-patients. Body composition in Black-patients, and NSCLC subtypes more commonly seen in Asian-patients and never-smokers, may account for differences in these BMI-OS relationships.

6.
JNCI Cancer Spectr ; 4(5): pkaa035, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33134820

RESUMO

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.

7.
Public Health Nutr ; : 1-6, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33234187

RESUMO

OBJECTIVE: To examine children's sugar-sweetened beverage (SSB) and water intakes in relation to implemented intervention activities across the social ecological model (SEM) during a multilevel community trial. DESIGN: Children's Healthy Living was a multilevel, multicomponent community trial that reduced young child obesity (2013-2015). Baseline and 24-month cross-sectional data were analysed from nine intervention arm communities. Implemented intervention activities targeting reduced SSB and increased water consumption were coded by SEM level (child, caregiver, organisation, community and policy). Child SSB and water intakes were assessed by caregiver-completed 2-day dietary records. Multilevel linear regression models examined associations of changes in beverage intakes with activity frequencies at each SEM level. SETTING: US-Affiliated Pacific region. PARTICIPANTS: Children aged 2-8 years (baseline: n 1343; 24 months: n 1158). RESULTS: On average (± sd), communities implemented 74 ± 39 SSB and 72 ± 40 water activities. More than 90 % of activities targeted both beverages together. Community-level activities (e.g. social marketing campaign) were most common (61 % of total activities), and child-level activities (e.g. sugar counting game) were least common (4 %). SSB activities across SEM levels were not associated with SSB intake changes. Additional community-level water activities were associated with increased water intake (0·62 ml/d/activity; 95 % CI: 0·09, 1·15) and water-for-SSB substitution (operationalised as SSB minus water: -0·88 ml/d/activity; 95 % CI: -1·72, -0·03). Activities implemented at the organization level (e.g. strengthening preschool wellness guidelines) and policy level (e.g. SSB tax advocacy) also suggested greater water-for-SSB substitution (P < 0·10). CONCLUSIONS: Community-level intervention activities were associated with increased water intake, alone and relative to SSB intake, among young children in the Pacific region.

8.
Int J Cancer ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33105052

RESUMO

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

9.
Cancer Epidemiol Biomarkers Prev ; 29(12): 2735-2739, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32967863

RESUMO

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.

10.
Cancer Epidemiol Biomarkers Prev ; 29(12): 2729-2734, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32972968

RESUMO

BACKGROUND: Auto-antibodies to tumor suppressor p53 are found in a subset of patients with colorectal cancer. A recent prospective study in the United States has reported a significant 1.8-fold increased odds for colorectal cancer development with prediagnostic seropositivity to p53. In this study, we sought to examine this association in a U.S. colorectal cancer cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early biomarker for colorectal cancer. METHODS: Auto-antibodies to p53 were measured in prediagnostic blood samples of 3,702 incident colorectal cancer cases and 3,702 controls, matched by age, race, and sex, from 9 U.S. prospective cohorts. The association of seropositivity to p53 with colorectal cancer risk, overall and by time between blood draw and diagnosis, was determined by conditional logistic regression. RESULTS: Overall, 5% of controls and 7% of cases were seropositive to p53, resulting in a statistically significant 33% increased colorectal cancer risk [odds ratio (OR), 1.33; 95% confidence interval (CI), 1.09-1.61]. By follow-up time, the association was only significant with colorectal cancer diagnoses within 4 years after blood draw (OR, 2.27; 95% CI, 1.62-3.19), but not thereafter (OR, 0.97; 95% CI, 0.76-1.24). CONCLUSIONS: In this large consortium of prospective cohorts, we found that prediagnostic seropositivity to tumor suppressor p53 was significantly associated with an over 2-fold increased odds of developing colorectal cancer within 4 years after blood draw. IMPACT: Our finding suggests that p53 seropositivity may not be a useful predictor of long-term colorectal cancer risk; however, it might be considered as a marker to aid in the early diagnosis of colorectal cancer.

11.
Nutrients ; 12(10)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977670

RESUMO

This study aims to evaluate whether incorporating gender differences in portion sizes as part of quantifying a food frequency questionnaire influences the association of total energy intake with mortality. The analysis included 156,434 participants (70,142 men and 86,292 women) in the Multiethnic Cohort Study, aged 45-75 years at baseline. A total of 49,728 deaths were identified during an average follow-up of 18.1 years. Total energy intake and percentage energy from macronutrients were calculated using original portion sizes (PSs) and gender specific (GS)-PS and were divided into quintiles for men and women. The associations of total energy intake and percentage energy from macronutrients with all-cause, cardiovascular disease (CVD), and cancer mortality were examined using Cox regression with adjustment for potential confounders. Mean ± standard deviation daily total energy intake using original-PS was 2449 ± 1135 kcal for men and 1979 ± 962 kcal for women; using GS-PS was 1996 ± 884 kcal for men and 1595 ± 731 kcal for women. For men, the hazard ratios (HRs) (95% confidence intervals) for all-cause, CVD, and cancer comparing the highest to the lowest quintile of total energy intake were 1.05 (1.00-1.10), 1.07 (0.99-1.16), 1.03 (0.95-1.13) using original-PS and 1.07 (1.02-1.12), 1.11 (1.03-1.20), 1.02 (0.94-1.12) using GS-PS, respectively. For women, the corresponding HRs were 1.03 (0.98-1.09), 0.99 (0.91-1.08), 1.10 (1.00-1.21) using original-PS and 1.06 (1.01-1.12), 1.02 (0.94-1.12), 1.07 (0.97-1.18) using GS-PS. Both versions of percentage energy from total fat were associated with an increased risk of all-cause, CVD, and cancer mortality; on the other hand, both versions of percentage energy from carbohydrate showed inverse associations with all-cause, CVD, and cancer mortality in both men and women. When using original-PS and GS-PS, the estimated total energy intake differed, resulting in marginal differences in the associations of total energy intake with all-cause, CVD, and cancer mortality.

12.
Cancer Epidemiol Biomarkers Prev ; 29(10): 2019-2025, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32732248

RESUMO

BACKGROUND: Incidence rates of epithelial ovarian cancer (EOC) vary across racial/ethnic groups, yet little is known about the impact of hormone-related EOC risk factors in non-Whites. METHODS: Among 91,625 female Multiethnic Cohort Study participants, 155 incident EOC cases were diagnosed in Whites, 93 in African Americans, 57 in Native Hawaiians, 161 in Japanese Americans, and 141 in Latinas. We used Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between race/ethnicity and EOC risk and between hormone-related factors and EOC risk across racial/ethnic groups. RESULTS: Compared with Whites, African Americans and Japanese Americans had a lower multivariable-adjusted EOC risk; Native Hawaiians had a suggestive higher risk. Parity and oral contraceptive (OC) use were inversely associated with EOC risk (P int race/ethnicity ≥ 0.43); associations were strongest among Japanese Americans (e.g., ≥4 vs. 0 children; HR = 0.45; CI, 0.26-0.79). Age at natural menopause and postmenopausal hormone (PMH) use were not associated with EOC risk in the overall population, but were positively associated with risk in Latinas (e.g., ≥5 years vs. never PMH use; HR = 2.13; CI, 1.30-3.49). CONCLUSIONS: We observed strong associations with EOC risk for parity and OC use in Japanese Americans and PMH use and age at natural menopause in Latinas. However, differences in EOC risk among racial/ethnic groups were not fully explained by established hormone-related risk factors. IMPACT: Our study indicates there are racial/ethnic differences in EOC risk and risk factors, and could help improve prevention strategies for non-White women.

13.
Nutrients ; 12(9)2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32825433

RESUMO

This study is part of the Children's Healthy Living program in U.S. Affiliated Pacific region. The objectives were to estimate overweight and obesity (OWOB) prevalence and identify possible related risk factors among ethnic groups in Guam. In 2013, 865 children (2-8 years) were recruited via community-based sampling from select communities in Guam. Children's demographic and health behavior information; dietary intake; and anthropometric measurements were collected. Logistic regression, odds ratio, t-tests, and chi-square tests were used to determine differences and assess covariates of OWOB. The results indicate that 58% of children were living below the poverty level, 80% were receiving food assistance, and 51% experienced food insecurity. The majority of children surveyed did not meet recommendations for: sleep duration (59.6%), sedentary screen-time (83.11%), or fruit (58.7%) and vegetable (99.1%) intake, and consumed sugar sweetened beverages (SSB) (73.7%). OWOB affected 27.4% of children. Children affected by OWOB in this study were statistically more likely (p = 0.042) to suffer from sleep disturbances (p = 0.042) and consume marginally higher amounts (p value = 0.07) of SSB compared to children with healthy weight. Among Other Micronesians, children from families who considered themselves 'integrated' into the culture were 2.05 (CI 0.81-5.20) times more likely to be affected by OWOB. In conclusion, the OWOB prevalence among 2-8-year-olds in Guam was 27.4%; and compared with healthy weight children, children with OWOB were more likely to have educated caregivers and consume more SSBs. Results provide a basis for health promotion and obesity prevention guidance for children in Guam.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32801014

RESUMO

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.

15.
Hepatol Commun ; 4(8): 1112-1123, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32766472

RESUMO

The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population-specific genetic variants associated with liver fat. We conducted a genome-wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population-based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin-like phospholipase domain containing 3 (PNPLA3) at 22q13 was confirmed to be associated with percent liver fat (P = 3.52 × 10-15) but more strongly in women than men (P heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.028; P = 0.009) and circulating levels of insulin (beta = 0.022; P = 0.020) and alanine aminotransferase (beta = 0.016; P = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [LMBRD1] and collagen type XIX alpha 1 chain [COL19A1] (P = 1.42 × 10-8) was also observed. Rs7724941 was associated with HOMA-IR (beta = 0.12; P = 0.0005), insulin (beta = 0.11; P = 0.0003), triglycerides (beta = 0.059; P = 0.01), high-density lipoprotein (beta = -0.046; P = 0.04), and sex hormone binding globulin (beta = -0.084; P = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). Conclusion: We replicated the PNPLA3 rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association.

16.
Ethn Health ; : 1-14, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32508127

RESUMO

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

17.
Hum Mol Genet ; 29(13): 2275-2284, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32491157

RESUMO

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.

18.
Hawaii J Health Soc Welf ; 79(6 Suppl 2): 40-44, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32596677

RESUMO

Breast cancer is the second leading cause of cancer-related death among women on Guam and Hawai'i. Breast cancer incidence rates are described here for the multiethnic population in Guam, a United States (US) Pacific island territory, and compared to Hawai'i and other US populations, to understand the risk by age and race/ethnic group in this understudied group. The study included all breast cancer cases (n=576) reported to the Guam Cancer Registry, all breast cancer cases (n=8345) reported to the Hawai'i Tumor Registry and all breast cancer cases (n=678,637) reported to the Surveillance, Epidemiology, and End Results program from 2000 to 2009. Cumulative incidence rates by age were calculated for two time periods: 2000-2004 and 2005-2009. Differences were seen in cumulative incidence rates by age, ethnicity, and place of residence. Cumulative incidence rates by age 40 were the highest (0.7%) among Filipinos in Guam but, after age 40, the rates for Chamorros (indigenous Pacific Islanders of Guam) increased rapidly. The lifetime cumulative incidence rates were the highest for Chamorros in Guam (15.3%), close to the US rate (15.5%). Results were similar for 2005-2009. Women in Guam are at high risk for breast cancer, with the indigenous Chamorros having the highest risk, and the most prevalent Asian group of Filipinos, having a younger age at diagnosis. These patterns are similar to the comparable Pacific Islander and Filipino populations in Hawai'i and the US generally.

19.
Br J Cancer ; 123(5): 793-802, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32555365

RESUMO

BACKGROUND: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. METHODS: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests. RESULTS: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). CONCLUSIONS: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

20.
Cancer Epidemiol Biomarkers Prev ; 29(7): 1283-1289, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32371551

RESUMO

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Coleta de Dados/métodos , Pandemias , Pneumonia Viral/epidemiologia , Software , Infecções por Coronavirus/diagnóstico , Humanos , Modelos Biológicos , Pneumonia Viral/diagnóstico , Saúde Pública , Smartphone , Reino Unido/epidemiologia , Estados Unidos/epidemiologia
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