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.

摘要 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/民族 人们观察到了PC发病率的差异，美国黑人的发病率比白人高30%。 夏威夷原住民和日裔美国人的个人电脑患病率在过去20年里一直在上升，而且 超过了白人，但还没有进行研究来确定这种上升的原因(S)。在……里面 大型前瞻性多种族队列研究(MEC；N&GT；200,000)，我们观察到在 种族/民族人群中的PC发病率，与非裔美国人相比，非洲裔美国人的发病率高39% 白色的。研究发现，夏威夷原住民的这一比例最高，比白人高出74%。 而日裔美国人的比率比白人高32%，而拉美裔人的比率与白人相似。我们期待着 风险因素患病率的种族差异很可能解释了观察到的PC的种族差异 发病率。然而，到目前为止，很少有研究包括非裔美国人，也没有研究包括 日裔美国人、夏威夷原住民或拉美人；因此，个人电脑差异背后的因素仍然不确定。 这项研究的目标是找出解释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额外风险。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对观察到的 PC发病率的种族/民族差异。为了检验我们的假设，我们将充分利用这种典型的生活方式 和MEC的基因数据，MEC是一个长期存在的种族多样化的潜在队列，有20万名非洲人 美国人、拉美人、夏威夷原住民、日本人和白人参与者于20世纪90年代初在加利福尼亚州成立。S 还有夏威夷。MEC在解决PC发病率的种族/民族差异方面具有独特的地位，有2,100 经过20年的随访，并有详细的生活方式和暴露数据的PC确诊病例 在所有人口中以一致的方式收集数据，以便进行有效的种族比较。我们的具体目标 1)量化已知的和潜在的/可疑的危险因素与PC之间的种族/民族相关性 非洲裔美国人、日裔美国人、拉丁裔、夏威夷原住民和白人的发病率；2)确定 在目标1中确认或发现的危险因素是否与观察到的PC的种族差异有关 3)研究已知的常见基因变异与非洲人前列腺癌风险之间的关系 美国人、日裔美国人、拉丁裔和夏威夷原住民，并建立量化风险模型进行比较 遗传风险在与这些标记等位基因相关的人群中的分布。通过利用 现有资源/基础设施，这项研究将以高效和经济高效的方式审查可能 助长了PC中的种族/民族差异。由于缺乏有效的治疗和低存活率， 识别可更改的风险因素对于减轻PC负担至关重要；这对少数人来说更是至关重要 风险较大且可能获得护理的机会有限的人群。