Epidemiologic Study of Hepatocellular Carcinoma in the US

美国肝细胞癌的流行病学研究

• 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
• 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

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。该疾病的五年存活率仅为10％。在美国，HCC的发生率一直在稳步上升。 SEER数据显示，在过去30年中，该速率翻了一番。尽管HCC在美国仍然很少见，但发病率的迅速增加引起了人们对疾病潜在风险可能发生变化的担忧。新兴的证据表明，高热量饮食和身体不活动的生活方式引起的能量失衡的生物学不平衡可能在HCC的病因中起作用。这种生活方式与HCC的这种可能的联系在公共卫生中具有重要意义，因为我们社会中超重和肥胖的患病率不断增加，这表明HCC的发生率可能会继续相应上升。证据还表明，与细胞增殖，细胞凋亡，对病毒感染，炎症和其他与癌症相关的细胞活性有关的低渗透率单核苷酸多态性反映出的宿主易感性。为了确认能源失衡是否独立参与HCC的病因，并确定哪些遗传易感因素与HCC风险相关，我们提出了康涅狄格州和新泽西州HCC的流行病学研究。该研究将检查美国人中HCC的所有已知和怀疑危险因素，并评估HCC与与能量平衡有关的生活方式因素的可能联系。该研究还将评估基因组范围内的遗传多态性，以确定宿主对HCC的敏感性。能量失衡和肝炎病毒感染之间的协同相互作用将是这项研究的另一个重点。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确定招募1,250例HCC病例。招募年龄，性别，种族和州的案件频率匹配的两千和五百人的控制也将被招募。控制对象将通过随机数字拨号从州居民随机选择。将收集问卷的信息和生物标本，以评估HCC已知和可疑危险因素的暴露，并检查可能的遗传敏感性和宿主环境相互作用。该研究将在美国产生有关HCC的有价值的信息，并可能确定导致美国HCC上升的风险因素。 公共卫生相关性：制定了研究建议是为了调查美国人中肝细胞癌（HCC）的病因，并确定在美国过去30年中HCC发病率持续上升的原因。该研究将在康涅狄格州和新泽西州招募1,250例HCC病例，以及2,500个人口控制，频率匹配年龄，性别，种族和居住区。将研究已知和怀疑的HCC危险因素，包括生活方式因素，肝炎病毒感染，饮食，病史，癌症家族史以及单核苷酸多态性，这些核苷酸多态性将在1,000例和2,000例控制中通过全基因组扫描进行评估，并在另外800例和1,100例控制中进行其他验证。