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

描述（由申请人提供）：肝细胞癌（HCC）是第二大致命癌症，5年生存率<12%，中位生存期为8个月。在过去的30年里，美国的HCC发病率增加了两倍。在美国的所有主要癌症中，HCC的发病率和死亡率的年增长率分别排在第二位和第一位。HCC发病率的种族/民族差异一直被观察到，在亚洲/太平洋岛民、西班牙裔和非洲裔美国人中发病率较高。已知HCC危险因素（如病毒性肝炎感染和酒精滥用）患病率的种族间差异可能解释了HCC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。鉴于大部分HCC仍未得到解释，有必要进行研究，特别是在高危少数人群中，以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，被怀疑是HCC的新危险因素。他们对这些人群中HCC发病率上升的贡献尚不清楚。我们建议在一项大型、前瞻性和特征明确的多民族队列研究（MEC）中进行全面分析，以确定解释HCC风险中种族/民族差异的因素，特别是在拉美裔和非裔美国人中观察到的超额风险。MEC独特地由5个种族/民族组成（约21.5万名非裔美国人、拉丁裔美国人、日裔美国人、夏威夷原住民和高加索人），他们的HCC发病率各不相同。在19年期间（1993-2012）诊断出800多例HCC事件，并在该队列中收集了综合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HCC发病率的种族/民族差异是否可以用已知和推定的HCC危险因素分布的种族间差异来解释；2)研究肥胖和代谢综合征的其他关键因素与HCC风险之间的关联是否在种族/民族之间存在差异，以及这种关联是否被已知的HCC危险因素所修正。发病率的增加加上HCC在少数群体中的高死亡率构成了一个新出现的重大公共卫生问题。这项拟议的研究将是首个以人群为基础的HCC前瞻性研究，其中包括大量拉丁裔、非裔美国人、亚洲人和白种人。确定解释HCC风险的种族/民族差异的病因因素可以大大提高目前对美国HCC病因学的理解，有助于解释为什么美国西班牙裔和非洲裔美国人的发病率显著上升，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，从而早期诊断和提高生存率。

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.