Full Project II: Novel Risk Factors and Disease Associations of Liver Cancer in Guam
完整项目 II:关岛肝癌的新危险因素和疾病关联
基本信息
- 批准号:10084113
- 负责人:
- 金额:$ 9.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-28 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:16S ribosomal RNA sequencingAddressAlcoholsArecaBacterial GenesBiological MarkersBloodCase-Control StudiesChronic Hepatitis CCircadian RhythmsCollaborationsDataDiabetes MellitusDiseaseEarly InterventionEtiologyFatty LiverFatty acid glycerol estersFibrosisGenesGlucoseGuamHepatitis C virusHigh PrevalenceIncidenceLinkLipidsLiverLiver CirrhosisLiver FibrosisLiver diseasesMalignant NeoplasmsMalignant neoplasm of liverMasticationMeasuresMediatingMetabolicMetabolic DiseasesNative-BornNutsObesityOralOral cavityOral healthPacific IslandsPathogenicityPatient Self-ReportPatientsPatternPeriodontal DiseasesPopulationPreventive InterventionPrimary carcinoma of the liver cellsQuestionnairesResearchRiskRisk FactorsRoleSamplingSeveritiesSleepSleep Apnea SyndromesSleep disturbancesSnoringStratificationUnited StatesViral hepatitiscancer health disparitychronic liver diseasecircadian pacemakerclinical examinationcommensal bacteriacryptochromedysbiosishealth equityinsulin signalingmRNA Expressionmicrobialmortalitynon-alcoholic fatty liver diseasenovelnovel strategiesoral microbiomesecondary outcomesleep abnormalitiessleep quantity
项目摘要
PROJECT SUMMARY/ABSTRACT
The US territory of Guam has a staggeringly high burden of liver cancer with incidence and mortality more than
twice that of overall rates in the United States (US) where rates have nearly tripled over the past three decades.
Excess risk is most prominent among CHamorus who are the native people of Guam, comprising 42% of the
population. Hepatocellular carcinoma (HCC), the primary form of liver cancer, develops entirely within the context
of progressive chronic liver disease (CLD) characterized by advancing levels of fibrosis. Thus, there is an urgent
need to understand the etiology of progressive CLD in CHamorus and to identify novel strategies and targets for
prevention and early intervention. Our proposed research will address whether oral dysbiosis and sleep/circadian
rhythm disturbance contribute to liver fibrosis through glucose and lipid dysmetabolism and the potential
modifying effect of other exposures. We propose a case-control study of 300 liver fibrosis cases and 300 matched
controls among CHamorus in Guam. Liver fibrosis, a well-established precursor of liver cancer, as well as liver
steatosis as a secondary outcome, will be measured by transient elastrography (Fibroscan).
The Specific Aims of Full Project II are to:
1) Evaluate the association of oral dysbiosis with liver fibrosis and steatosis. Oral dysbiosis will be defined as
deleterious patterns of the oral microbiome and/or the presence of periodontal disease. We will perform bacterial
16S rRNA sequencing to measure oral bacterial diversity and composition. We will determine periodontal
disease by clinical examination and self-report. The association between oral dysbiosis and liver fibrosis, with or
without stratification by steatosis grades, will be evaluated; the potential modifying effects of other exposures
(e.g., betel nut chewing, viral hepatitis, alcohol) and the mediating effects of glucose and lipid dysmetabolism
will be assessed. We hypothesize that having moderate to severe liver fibrosis is associated with: 1a) reduced
oral microbial diversity, enriched pathogenic and depleted commensal bacteria, and aberrations in insulin-
signaling bacterial genes; 1b) the presence and severity of periodontal disease; and 1c) oral dysbiosis through
and independently of glucose/lipid dysmetabolism.
2) Evaluate the associations of sleep (quantity and quality) and circulating Mrna expression levels of circadian
clock genes with liver fibrosis and steatosis. We will determine sleep duration and quality using validated
questionnaires and analyze the expression of the period (Per1, Per2, Per3) and cryptochrome (Cry2) genes in
blood as a biomarker of circadian rhythm. We hypothesize that liver fibrosis is associated with: 2a) short sleep
duration and sleep apnea; 2b) reduced expression of the clock genes; and 2c) sleep/circadian rhythm
disturbances through and independently of glucose/lipid dysmetabolism.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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BRENDA Y HERNANDEZ其他文献
BRENDA Y HERNANDEZ的其他文献
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{{ truncateString('BRENDA Y HERNANDEZ', 18)}}的其他基金
UHI COBRE: P1: MOL EPIDEMIOL & NATURAL HISTORY OF HPV IN HETEROSEXUAL MEN
UHI COBRE:P1:MOL 流行病
- 批准号:
8168408 - 财政年份:2010
- 资助金额:
$ 9.53万 - 项目类别:
Full Project II: Novel Risk Factors and Disease Associations of Liver Cancer in Guam
完整项目 II:关岛肝癌的新危险因素和疾病关联
- 批准号:
10490855 - 财政年份:2009
- 资助金额:
$ 9.53万 - 项目类别:
(1/2) Pacific Island Partnership for Cancer Health Equity (PIPCHE)
(1/2) 太平洋岛屿癌症健康公平伙伴关系 (PIPCHE)
- 批准号:
10266798 - 财政年份:2009
- 资助金额:
$ 9.53万 - 项目类别:
(1/2) Pacific Island Partnership for Cancer Health Equity (PIPCHE)
(1/2) 太平洋岛屿癌症健康公平伙伴关系 (PIPCHE)
- 批准号:
10490850 - 财政年份:2009
- 资助金额:
$ 9.53万 - 项目类别:
(1/2) Pacific Island Partnership for Cancer Health Equity (PIPCHE)
(1/2) 太平洋岛屿癌症健康公平伙伴关系 (PIPCHE)
- 批准号:
10084110 - 财政年份:2009
- 资助金额:
$ 9.53万 - 项目类别:
Full Project II: Novel Risk Factors and Disease Associations of Liver Cancer in Guam
完整项目 II:关岛肝癌的新危险因素和疾病关联
- 批准号:
10266801 - 财政年份:2009
- 资助金额:
$ 9.53万 - 项目类别:
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