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

调查胰腺癌发病率种族/民族差异的原因

• 批准号: 9300756
• 负责人: VERONICA WENDY SETIAWAN
• 金额: $ 39.51万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-06 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9300756
• 关键词: Address; African American; Alcohol consumption; Alleles; Antidepressive Agents; Antidiabetic Drugs; California; Cancer Burden; Cessation of life; Cholelithiasis; Cohort Studies; Contraceptive Usage; Data; Databases; Diabetes Mellitus; Diet; Dietary Factors; Employee Strikes; Epidemiology; Family history of; Fibrinogen; Genetic; Genetic Risk; Goals; Hawaii; Health; Health Services Accessibility; Hormone use; Hormones; Hospitalization; Hypersensitivity; Incidence; Japanese American; Japanese Population; Latino; Life Style; Lipids; Malignant Neoplasms; Malignant neoplasm of pancreas; Medical; Medicare; Menopause; Minority; Modeling; Native Hawaiian; Nested Case-Control Study; Nutrient; Obesity; Oral Contraceptives; Pancreatitis; Participant; Patients; Pharmaceutical Preparations; Physical activity; Population; Population Attributable Risks; Positioning Attribute; Prevalence; Prospective cohort; Questionnaires; Recording of previous events; Research Infrastructure; Resources; Risk; Risk Factors; Role; Smoking; Survival Rate; Testing; Weight; Woman; cancer diagnosis; cancer health disparity; cancer risk; cigarette smoking; cohort; cost; disorder risk; effective therapy; ethnic difference; ethnic diversity; follow-up; genetic variant; men; modifiable risk; mortality; neoplasm registry; non-genetic; parity; prospective; racial and ethnic; racial and ethnic disparities; survivorship

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.

抽象的 胰腺癌（PC）是最致命的癌症之一，5年生存率为7％。著名的种族/种族 已经观察到PC发病率的差异，与白人相比，美国黑人的比率高30％。 在过去的二十年中 超过了白人，但尚未进行研究以识别发生率上升的原因。在 大型的前瞻性多民族队列研究（MEC; n> 200,000），我们观察到了高度显着的差异 跨种族/民族人口的PC发病率，非洲裔美国人的比率高39％ 白人。观察到夏威夷原住民在队列中的比率最高，比白人高74％ 虽然日裔美国人的速度高32％，而拉丁美洲人的比率与白人相似。我们期望这一点 风险因素患病率的种族间差异可能解释了PC的观察到的种族差异 发病率。但是，迄今为止，很少有研究包括非洲裔美国人，没有研究包括 日裔美国人，夏威夷人或拉丁美洲人；因此，PC差异的基础因素仍然不确定。 这项研究的目的是确定解释PC发病率的种族/种族差异的因素，尤其是 在非洲裔美国人，日裔美国人和夏威夷原住民中观察到的过多风险。我们假设这一点 除了已知的危险因素外，宿主遗传因素和未知的非遗传因素有助于观察到 PC发病率的种族/种族差异。为了检验我们的假设，我们将利用良好的生活方式 和MEC的遗传数据，这是一个长期以来多样化的前瞻性队列，> 200,000非洲 美国，拉丁美洲人，本地夏威夷人，日本和白人参与者于1990年代初在加利福尼亚建立 和夏威夷。 MEC的独特位置可以解决PC发病率的种族/种族差异，> 2,100 被诊断出> 20年的随访和详细的生活方式和曝光数据的PC的事件病例 在所有人群中以一致的方式收集，以允许有效的种族比较。我们的具体目标 是：1）量化已知和潜在/可疑风险因素的种族/种族特异性关联 非洲裔美国人，日裔美国人，拉丁美洲人，夏威夷人和白人的发病率； 2）确定 AIM 1中确认或发现的风险因素是否有助于PC中观察到的种族差异 发病率； 3）表征已知的普通遗传变异与非洲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来比较 与这些标记等位基因相关的人群中遗传风险的分布。通过利用 现有的资源/基础设施，这项研究将有效，成本效率地检查可能 在PC中有助于种族/种族差异。由于缺乏有效的治疗和较低的生存权， 确定可修改的风险因素对于减轻PC负担至关重要。这对少数民族更为重​​要 面临更大风险且可能有限的护理机会的人群。