Investigating the cause of racial/ethnic disparity in pancreatic cancer incidence

摘要 胰腺癌（PC）是最致命的癌症之一，5年生存率为7%。显著种族/族裔 已经观察到PC发病率的差异，美国黑人的发病率比白人高30%。 在过去的二十年里，夏威夷原住民和日裔美国人的PC率一直在上升， 超过了白人，但没有进行任何研究来确定这种发病率上升的原因。在 在大型前瞻性多种族队列研究（MEC; N> 200，000）中，我们观察到 各种族/民族人群的PC发病率，与非裔美国人相比，非裔美国人的PC发病率高出39%。 白人据观察，夏威夷原住民的比例最高，比白人高出74 而日裔美国人的比率高出32%，拉丁裔的比率与白人相似。我们预计 危险因素患病率的种族间差异可能解释PC中观察到的种族差异 发病率。然而，到目前为止，很少有研究包括非洲裔美国人，也没有研究包括 日裔美国人、夏威夷原住民或拉丁美洲人;因此，PC差异的潜在因素仍然不确定。 本研究的目的是确定解释PC发病率种族/民族差异的因素，特别是 在非裔美国人、日裔美国人和夏威夷原住民中观察到的过度风险。我们假设 除了已知的风险因素外，宿主遗传因素和未知的非遗传因素也有助于观察到的 PC发生率的种族/民族差异。为了验证我们的假设，我们将利用 MEC是一个长期存在的种族多样性前瞻性队列， 美国人、拉丁美洲人、夏威夷原住民、日本人和白色参与者于20世纪90年代初在加州成立 和夏威夷。MEC在解决PC发病率的种族/民族差异方面具有独特的优势， 随访时间超过20年并有详细生活方式和暴露数据的PC发病病例 在所有人群中以一致的方式收集，以进行有效的种族比较。我们的具体目标 是：1）量化已知和潜在/疑似风险因素与PC的种族/民族特异性关联 非裔美国人、日裔美国人、拉丁美洲人、夏威夷原住民和白人的发病率; 2）确定 目标1中确认或发现的风险因素是否有助于观察到的PC种族差异 3）描述非洲人中已知的常见遗传变异与PC风险的关联。 美国人、日裔美国人、拉丁美洲人和夏威夷原住民，并建立一个定量风险模型进行比较 与这些标记等位基因相关的遗传风险在人群中的分布。通过利用 现有资源/基础设施，本研究将有效和具有成本效益地检查可能 导致PC中的种族/民族差异。由于缺乏有效的治疗和低生存率， 确定可改变的风险因素对于减少PC负担至关重要;这对于少数群体来说更为重要。 风险更大、获得护理的机会可能有限的人群。

ABSTRACT Pancreatic cancer (PC) is one of the deadliest cancers with a 5-year survival rate of 7%. Notable racial/ethnic differences in PC incidence have been observed, with U.S. blacks having 30% higher rates compared to whites. The rates of PC in Native Hawaiians and Japanese Americans have been rising in past two decades and have surpassed those of whites, but no study has been conducted to identify the cause(s) of this rising incidence. In the large prospective Multiethnic Cohort Study (MEC; N>200,000) we observed highly significant differences in PC incidence across racial/ethnic populations, with African Americans having 39% higher rates compared to whites. Native Hawaiians are observed to have the highest rates in the cohort that are 74% higher than whites while rates in Japanese Americans are 32% higher and rates in Latinos are similar to whites. We expect that inter-ethnic differences in risk factor prevalence are likely to explain the observed ethnic differences in PC incidence. However, to date, few studies have included African Americans and no studies have included Japanese Americans, Native Hawaiians, or Latinos; thus, the factors underlying PC disparities remain undefined. The goal of this study is to identify factors that explain racial/ethnic disparities in PC incidence, particularly the excess risks observed in African Americans, Japanese Americans, and Native Hawaiians. We hypothesize that in addition to known risk factors, host genetic factors and unknown non-genetic factors contribute to the observed racial/ethnic differences in PC incidence. To test our hypothesis, we will leverage the well-characterized lifestyle and genetic data of the MEC, a long-standing ethnically diverse prospective cohort of >200,000 African American, Latino, Native Hawaiian, Japanese and white participants established in the early 1990's in California and Hawaii. The MEC is uniquely positioned to address racial/ethnic disparities in PC incidence, with >2,100 incident cases of PC diagnosed over >20-years of follow-up and with detailed lifestyle and exposure data collected in a consistent fashion amongst all populations to permit valid ethnic comparisons. Our specific aims are: 1) To quantify racial/ethnic-specific associations of known and potential/suspected risk factors with PC incidence in African Americans, Japanese Americans, Latinos, Native Hawaiians, and whites; 2) To determine whether the risk factors confirmed or discovered in Aim 1 contribute to the observed ethnic differences in PC incidence; 3) To characterize the association of known common genetic variants with PC risk in African Americans, Japanese Americans, Latinos, and Native Hawaiians and build a quantitative risk model to compare the distribution of genetic risks across populations associated with these marker alleles. By leveraging the existing resources/infrastructure, this study will efficiently and cost-effectively examine multiple factors that may contribute to racial/ethnic disparities in PC. Because of the lack of effective treatment and low survivorship, identifying modifiable risk factors is critical in reducing PC burden; this is even more crucial for minority populations who are at greater risk and are likely to have limited access to care.