Investigating the cause of racial/ethnic disparity in hepatocellular cancer risk

简介(申请人提供)：肝细胞癌是第二大致死性癌症，5年生存率为12%，中位生存期为8个月。在过去的30年里，美国的肝癌发病率增加了两倍。在美国所有主要癌症中，肝癌的发病率和死亡率分别位居第二和唯一最大的年增幅。肝癌发病率的种族/民族差异一直被观察到，在亚洲人/太平洋岛民、西班牙裔和非裔美国人中出现了过高的发病率。已知的肝细胞癌危险因素(即病毒性肝炎感染和酗酒)患病率的种族间差异可以解释观察到的肝细胞癌发病率的种族/民族差异。然而，这些因素加在一起，只占美国疾病负担的一半。鉴于很大一部分肝癌仍未得到解释，有必要进行一项研究，特别是在高危少数人群中，确定这种致命癌症的病因。肥胖和II型糖尿病是代谢综合征的主要因素，在西班牙裔和非裔美国人中非常普遍，可能是肝细胞癌的新危险因素。他们对这些人群中不断上升的肝癌发病率的贡献尚不清楚。我们在一项大型、前瞻性和特征良好的多种族队列研究中提出了一项综合分析，以确定解释肝癌风险的种族/民族差异的因素(S)，特别是在拉美裔和非裔美国人中观察到的额外风险。MEC独特地由五个种族/民族组成(215,000名非裔美国人、拉丁裔、日裔美国人、夏威夷原住民和高加索人)，他们的肝癌发病率各不相同。在19年的时间里(1993-2012年)，已诊断出800多例肝细胞癌病例，并在该队列中收集了全面的基线和随访问卷数据、临床数据和诊断前血液样本。具体目的是：1)确定是否可以用已知和推定的肝癌危险因素分布的种族间差异来解释肝癌发病率的种族/民族差异；2)检查肥胖和代谢综合征的其他关键因素与肝癌风险之间的关联是否在种族/民族之间不同，以及这种关联(S)是否被已知的肝癌风险因素改变。不断增加的发病率，加上少数群体中肝癌的高死亡率，构成了一个新的重大公共卫生问题。这项拟议的研究将是第一项基于人群的肝癌前瞻性研究，其中包括相当数量的拉丁裔、非裔美国人、亚裔和高加索人。找出解释肝癌风险种族/民族差异的病因因素，可以极大地增强目前美国对肝癌病因学的了解，有助于解释为什么美国拉美裔和非裔美国人的发病率一直在显著上升，并对这种致命癌症的一级预防产生重大影响。此外，可以开发更有效的筛查，从而获得更早的诊断和更好的生存。

DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is the second most deadly cancer with a <12% five-year survival rate and 8 month median survival. HCC incidence has tripled in the US over the past three decades. Of all major cancers in the US, HCC has shown the second and single greatest annual percent increase in incidence and mortality, respectively. Racial/ethnic differences in HCC incidence have been consistently observed with excess rates seen among Asians/Pacific Islanders, Hispanics and African Americans. Inter-ethnic differences in the prevalence of known HCC risk factors (i.e. viral hepatitis infection and alcohol abuse) may explain the observed racial/ethnic differences in HCC incidence. However, taken together, these factors only account for half of disease burden in the US. Given that a large proportion of HCC remains unexplained, a study, especially in high-risk minority groups, to identify the etiologic factors for this fatal cancer is warranted. Obesity and type II diabetes, maor elements of metabolic syndrome, are highly prevalent in Hispanics and African Americans and suspected emerging risk factors for HCC. Their contribution to the rising HCC incidence in these populations is unknown. We propose a comprehensive analysis in a large, prospective and well- characterized Multiethnic Cohort Study (MEC) to identify factor(s) that explains racial/ethnic disparity in HCC risk, particularly the excess risk observed in Latinos and African Americans. The MEC is uniquely comprised of five racial/ethnic populations (>215,000 African Americans, Latinos, Japanese Americans, Native Hawaiians, and Caucasians) with varying HCC incidence rates. More than 800 incident cases of HCC have been diagnosed over a 19-year period (1993-2012) and comprehensive baseline and follow-up questionnaire data, clinical data, and pre-diagnostic blood samples have been collected in this cohort. The specific aims are: 1) to determine whether racial/ethnic differences in HCC incidence can be explained by inter-ethnic differences in the distribution of known and putative HCC risk factors; 2) to examine whether the association between obesity and other key elements of metabolic syndrome and HCC risk differs across racial/ethnic groups, and whether the association(s) is modified by known HCC risk factors. The increasing incidence coupled with HCC's high fatality rate among minority groups constitutes an emerging major public health problem. The proposed study will be the first population-based prospective study of HCC that includes a substantial number of Latinos, African Americans, Asians and Caucasians. Identifying etiologic factors that explain racial/ethnic differences in HCC risk could greatly enhance the current understanding of the HCC etiology in the US, help explain why the incidence has been rising significantly in US Hispanics and African Americans and have a significant impact on the primary prevention of this fatal cancer. In addition, more effective screening could be developed leading to earlier diagnosis and better survival.