EPIDEMIOLOGY OF HEPATOCELLULAR CARCINOMA & HEPATITIS B VIRUS IN 3 POPULATIONS

描述：(申请者描述)对60,984名男性进行的前瞻性研究 海门市的中国和19469名西非塞内加尔男子透露了14倍 海门市居民肝细胞癌死亡率较高(168 每100,000人中有12人)高于塞内加尔人(每100,000人中有12人)。即使是慢性 乙肝病毒感染是中国人肝细胞癌的主要危险因素 这两个人群的年龄调整后的慢性感染流行率约为 两个队列中都有20%的人。暴露于黄曲霉毒素，推测为主要危险因素 在塞内加尔人群中，肝癌的发病率也相似或更高。这个 成人乙肝病毒携带者中病毒血症(血清中的HBVDNA)的患病率 然而，中国人的生活要比塞内加尔人高得多 人口。然而，在中国队列中，研究开始时出现病毒血症 经过四年的随访，不是肝细胞癌的危险因素。 该项目的目标集中在可能导致 中国人、塞内加尔人和亚裔美国人中的肝癌风险 居住在费城地区的乙肝病毒携带者。继续追踪这些 三个队列将检验这一假设，即随着追踪时间的延长， 研究开始时的乙肝病毒血症和肝脏损害与 肝癌的个人风险以及黄曲霉毒素-B1(AFB1)-白蛋白加合物是 S S与病毒携带者和/或肝癌的发生 黄曲霉毒素F1的基因决定的劣解毒剂(与 项目2)。与土拨鼠的WHV研究密切合作 (项目3)，对1000名男性和女性乙肝病毒的密集纵向研究 将对这三个人群中的携带者进行以下检查：a)检查 乙肝病毒血清标志物稳定性的紊乱与急性 疾病、黄曲霉毒素暴露和/或病毒突变的副产物；b)化验 肝活检中的肝细胞周转和免疫反应；c)与之相关 衡量病毒载量；d)检查性别差异与 乙肝病毒血清标志物随时间的变化与降低女性乙肝患者患肝癌风险的关系 承运人。因为目前的研究表明，急性肝炎的一次发作 成年后乙肝病毒携带者和男性患肝癌的风险增加近一倍 年200例急性肝炎患者的病因及转归分析 海门市将以此为特色。 这项研究将导致对以下因素的新的理解 导致肝细胞癌和预防这种致命疾病的新策略。

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.