EPIDEMIOLOGY OF HEPATOCELLULAR CARCINOMA & HEPATITIS B VIRUS IN 3 POPULATIONS

肝细胞癌的流行病学

• 批准号: 6569661
• 负责人: William Thomas LONDON
• 金额: $ 7.89万
• 依托单位: FOX CHASE CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6569661
• 关键词: Africa; Asian Americans; China; United States; aflatoxins; biopsy; cancer risk; clinical research; disease /disorder etiology; disease carrier state; gender difference; hepatitis B virus group; hepatocellular carcinoma; human population study; human subject; liver disorder; longitudinal human study; neoplasm /cancer epidemiology; serology /serodiagnosis

Description: (Applicant's Description) Prospective studies of 60,984 men in Haimen City, China and 19,469 men in Senegal, west Africa revealed a 14-fold greater death rate from hepatocellular carcinoma (HCC) among the Haimen (168 per 100,000) than the Senegalese cohort (12 per 100,000). Even though chronic infection with hepatitis B virus (HBV) is the major risk factor for HCC in both populations, the age-adjusted prevalence of chronic infection is about 20% in both cohorts. Exposure to aflatoxin, a postulated major risk factor for HCC, is also similar or greater in the Senegalese population. The prevalence of viremia (HBV DNA in serum) among HBV carriers throughout adult life, however, is much higher among the Chinese than the Senegalese population. Nevertheless, within the Chinese cohort, viremia at study entry is not a risk factor for HCC after four years of follow-up. The aims of this project focus on factors that may account for variation in HCC risk in the Chinese and Senegalese cohorts and a cohort of Asian-American HBV carriers living in the Philadelphia area. Continued tracking of these three cohorts will test the hypothesis that with longer duration of follow-up, H B V v iremia and liver damage at study entry are associated with person-specific risks of HCC and that aflatoxin-B1 (AFB1)-albumin adducts are a s s ociated with development of HCC among viremic individuals and/or genotypically determined poor detoxifiers of AFB1 (in collaboration with Project 2). In close cooperation with the studies of WHV in woodchucks (Project 3), an intensive longitudinal study of 1000 male and female HBV carriers in these three populations will be conducted to: a) examine whether perturbations of the stability of HBV serum markers are associated with acute illnesses, aflatoxin exposure, and/or outgrowth of viral mutants; b) assay hepatocyte turnover and immune responses in liver biopsies; c) correlate these measures with viral load; d) examine the relationship of sex differences in changes in HBV serum markers over time to the lower HCC risk of female HBV carriers. Because present studies show that an episode of acute hepatitis in adulthood approximately doubles HCC risk among both HBV carriers and non-carriers, the causes and outcomes of 200 cases of acute hepatitis in Haimen City will be characterized. This research will lead to a new level of understanding of the factors that lead to HCC and to new strategies for the prevention of this lethal disease.

描述：（申请人的描述）针对 60,984 名男性的前瞻性研究 中国海门市和西非塞内加尔 19,469 名男性的 14 倍 海门人肝细胞癌 (HCC) 死亡率较高 (168 每 100,000 人）高于塞内加尔队列（每 100,000 人 12 人）。即使是慢性病 乙型肝炎病毒（HBV）感染是肝癌的主要危险因素 在这两个人群中，慢性感染的年龄调整患病率约为 两个队列中均为 20%。接触黄曲霉毒素，一个假定的主要危险因素 塞内加尔人群中 HCC 的比例也相似或更高。这 成人 HBV 携带者中病毒血症（血清中 HBV DNA）的患病率 然而中国人的生活比塞内加尔人要好得多 人口。然而，在中国队列中，研究进入时的病毒血症 经过四年的随访，不再是 HCC 的危险因素。 该项目的目标侧重于可能导致变化的因素 中国人和塞内加尔人群以及亚裔美国人人群中的 HCC 风险 居住在费城地区的乙肝病毒携带者。持续追踪这些 三个队列将检验以下假设：随着随访时间的延长， 进入研究时乙型肝炎病毒血症和肝损伤与 HCC 的个体特定风险以及黄曲霉毒素-B1 (AFB1)-白蛋白加合物 与病毒血症个体中 HCC 的发展相关和/或 基因型决定的 AFB1 解毒剂较差（与 项目2）。与土拨鼠 WHV 研究密切合作 （项目 3），对 1000 名男性和女性 HBV 进行的深入纵向研究 对这三个人群中的携带者进行以下检查： a) 检查是否 HBV 血清标志物稳定性的扰动与急性 疾病、黄曲霉毒素暴露和/或病毒突变体的生长； b) 测定 肝活检中的肝细胞更新和免疫反应； c) 将这些关联起来 病毒载量测量； d) 检查性别差异的关系 乙型肝炎病毒血清标志物随时间的变化可降低女性乙型肝炎病毒患肝癌的风险 载体。因为目前的研究表明，急性肝炎的发作 乙型肝炎病毒携带者和乙型肝炎病毒携带者成年后的肝癌风险大约增加一倍 非携带者，200例急性肝炎的原因和结果 海门市将成为特色城市。 这项研究将使人们对影响因素的理解达到一个新的水平。 导致 HCC 并制定预防这种致命疾病的新策略。