Epidemiologic Study of Hepatocellular Carcinoma in the US

美国肝细胞癌的流行病学研究

基本信息

批准号：
7984467
负责人：
HERBERT YU
金额：
$ 131.07万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7984467
关键词：
Affect Age Alcohol consumption American Apoptosis Body mass index Case-Control Studies Cell Proliferation Regulation Confounding Factors (Epidemiology)Connecticut Data Development Diet Diet Habits Disease Disease Outcome Energy Intake Enrollment Environment Epidemiologic Studies Etiology Factor Analysis Family Cancer History Family history of Frequencies Gender Gene Frequency Genetic Genetic Models Genetic Polymorphism Genetic Predisposition to Disease Haplotypes Hepatitis Viruses Immune response Incidence Inflammation Investigation Life Style Link Malignant Neoplasms Minor Modification New Jersey Non-Insulin-Dependent Diabetes Mellitus Obesity Overweight Penetrance Physical activity Play Population Control Predisposition Prevalence Primary carcinoma of the liver cells Public Health Questionnaires Race Recruitment Activity Research Proposals Risk Risk Factors Role Scanning Single Nucleotide Polymorphism Societies Specimen Study Subject Subgroup Survival Rate Validation Virus Diseases Weight Gain design digital disorder risk energy balance gene environment interaction genome wide association study genome-wide lifestyle factors population based public health relevance residence trend

项目摘要

DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is one of the most fatal malignancies in the world. Five-year survival rate of the disease is only 10%. The incidence of HCC has been steadily rising in the US. SEER data show that the rate more than doubled during the past 30 years. Although HCC is still rare in the US, the rapid increase in incidence has raised concerns on possible changes in underlying risk of the disease. Emerging evidence suggests that the biologic consequences of energy imbalance resulting from a lifestyle of high-calorie diets and physical inactivity may play a role in the etiology of HCC. This possible link of lifestyle to HCC has significant implications in public health because the increasing prevalence of overweight and obesity in our societies indicates that the incidence of HCC may continue to rise accordingly. Evidence also indicates significant host susceptibility to HCC reflected by low penetrance single nucleotide polymorphisms involved in regulation of cell proliferation, apoptosis, immune response to viral infection, inflammation, and other cancer-related cellular activities. To confirm if energy imbalance is independently involved in the etiology of HCC and to identify what genetic susceptible factors are associated with HCC risk, we propose an epidemiologic study of HCC in the states of Connecticut and New Jersey. The study will examine all known and suspected risk factors of HCC among Americans and evaluate the possible link of HCC to lifestyle factors related to energy balance. The investigation will also assess genetic polymorphisms in a genome- wide scope to determine host susceptibility to HCC. Synergistic interplay between energy imbalance and hepatitis virus infection will be another focus of this investigation. A population- based case-control study is designed to investigate these issues. The study will enroll 1,250 incident HCC cases through rapid case ascertainment. Two thousand and five hundred population controls with frequency match to cases on age, gender, race and state will also be recruited. The control subjects will be selected randomly from the state residents through random digital dialing. Questionnaire information and biologic specimens will be collected to assess the exposure of known and suspected risk factors of HCC and to examine possible genetic susceptibility and host- environment interaction. The study will generate valuable information on HCC in the US and may identify risk factors responsible for rising HCC in the US. PUBLIC HEALTH RELEVANCE: The research proposal is developed to investigate the etiology of hepatocellular carcinoma (HCC) among Americans and to identify the reasons responsible for the continuing rise of HCC incidence over the past 30 years in the US. The study will enroll 1,250 incident HCC cases in the states of Connecticut and New Jersey and 2,500 population controls with frequency match to age, gender, race and residence regions. Known and suspected risk factors of HCC will be investigated, including lifestyle factors, hepatitis virus infection, diet, medical history, family history of cancer, and single nucleotide polymorphisms which will be evaluated through genome-wide scan in 1,000 cases and 2,000 controls and additional validation in another 800 cases and 1,100 controls.

描述（由申请人提供）：肝细胞癌（HCC）是世界上最致命的恶性肿瘤之一。该病的五年生存率仅为10%。在美国，肝癌的发病率一直在稳步上升。 SEER 数据显示，过去 30 年这一比率增加了一倍多。尽管肝癌在美国仍然很少见，但发病率的迅速增加引起了人们对该疾病潜在风险可能发生变化的担忧。新的证据表明，高热量饮食和缺乏身体活动的生活方式导致能量失衡的生物学后果可能在肝癌的病因学中发挥作用。生活方式与 HCC 的这种可能联系对公共健康具有重大影响，因为我们社会中超重和肥胖的患病率不断增加，表明 HCC 的发病率可能会相应持续上升。证据还表明，宿主对 HCC 具有显着易感性，这反映在参与细胞增殖、凋亡、病毒感染免疫反应、炎症和其他癌症相关细胞活动调节的低外显率单核苷酸多态性上。为了确认能量失衡是否独立与 HCC 病因相关，并确定哪些遗传易感因素与 HCC 风险相关，我们建议在康涅狄格州和新泽西州进行一项 HCC 流行病学研究。该研究将检查美国人中所有已知和疑似的 HCC 危险因素，并评估 HCC 与能量平衡相关生活方式因素之间的可能联系。该研究还将评估全基因组范围内的遗传多态性，以确定宿主对 HCC 的易感性。能量失衡与肝炎病毒感染之间的协同相互作用将是本次调查的另一个重点。一项基于人群的病例对照研究旨在调查这些问题。该研究将通过快速病例查明招募 1,250 例 HCC 病例。还将招募 2500 名人口控制人员，其频率与年龄、性别、种族和州的案例相匹配。对照对象将通过随机数字拨号从州居民中随机选择。将收集问卷信息和生物样本，以评估已知和可疑的 HCC 危险因素的暴露情况，并检查可能的遗传易感性和宿主-环境相互作用。该研究将产生有关美国 HCC 的宝贵信息，并可能确定导致美国 HCC 发病率上升的风险因素。公共健康相关性：该研究提案旨在调查美国人肝细胞癌 (HCC) 的病因，并找出过去 30 年来美国 HCC 发病率持续上升的原因。该研究将纳入康涅狄格州和新泽西州的 1,250 例 HCC 病例以及 2,500 例对照人群，其频率与年龄、性别、种族和居住地区相匹配。将调查已知和疑似的 HCC 危险因素，包括生活方式因素、肝炎病毒感染、饮食、病史、癌症家族史和单核苷酸多态性，这些因素将通过对 1,000 例病例和 2,000 例对照以及其他样本进行全基因组扫描进行评估。在另外 800 个病例和 1,100 个对照中进行验证。