Delineating the underlying reasons for the racial disparity in gastric cancer incidence in the United States

描绘美国胃癌发病率种族差异的根本原因

• 批准号: 10518553
• 负责人: MEIRA EPPLEIN
• 金额: $ 72.48万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10518553
• 关键词: Affect; Antibiotics; Antibodies; Antibody Response; Asian population; Atrophic; Atrophic Gastritis; Bacteria; Biological; Biological Assay; Biological Markers; Bismuth; Black Populations; Body mass index; Cancer Etiology; Cells; Characteristics; Chronic stress; Clinical Trials; Cohort Studies; Communities; Country; Crowding; Data; Development; Diagnosis; Diagnostic; Diet; Disease; Far East; Funding; Future; Genes; Goals; Helicobacter Infections; Helicobacter pylori; Helicobacter pylori induced gastric cancer; Hepatitis B; Hepatitis C virus; Hispanic Populations; Household; Human papilloma virus 31; Immune response; Incidence; Individual; Infection; Infectious Agent; Inflammation; Knowledge; Laboratory Study; Lesion; Malignant Neoplasms; Mass Screening; Mediating; Minority Groups; Modeling; Neighborhoods; Nested Case-Control Study; Not Hispanic or Latino; Patients; Pattern; Pepsinogen A; Pepsinogens; Persons; Population Heterogeneity; Prevalence; Prevention Guidelines; Prospective cohort; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; Proteins; Proton Pump Inhibitors; Race; Risk; Risk Factors; Role; Screening for Gastric Cancer; Smoking; Smoking Status; Societies; Specimen; Stomach; Survival Rate; Time; United States; Virulence Factors; Women' s Health; black men; cancer diagnosis; cancer risk; carcinogenicity; cohort; cost effective; ethnic minority; falls; gastric cancer prevention; high risk; improved; individualized prevention; malignant stomach neoplasm; men; mortality; mortality disparity; multi-ethnic; novel; people of color; premalignant; racial and ethnic; racial difference; racial disparity; residential segregation; risk prediction; screening guidelines; social health determinants; tool

ABSTRACT The burden of gastric cancer falls disproportionately on racial/ethnic minorities in the US, with incidence rates among Blacks, Asians, and Hispanics two- to three-fold higher than that among non-Hispanic whites. Further, individuals who self- identify as belonging to any of these three groups are also more likely to die from gastric cancer, and comparing Black men to White men, specifically, this mortality disparity is greater than that for all other cancers. In the US, gastric cancer has a particularly low survival rate (32% at 5-years) as it is generally asymptomatic until late-stage, when treatment is no longer effective. Each year in the US, 26,000 people are diagnosed with gastric cancer, and over 10,000 people die of the disease. Moreover, the racial disparity in gastric cancer continues to grow over time. And yet, the underlying reasons for this racial disparity in gastric cancer incidence in the US are substantially understudied. The predominant cause of gastric cancer is infection with the common bacterium, Helicobacter pylori (H. pylori). H. pylori is more prevalent among people of color than non-Hispanic whites, and, in fact, H. pylori is the world’s single leading carcinogenic infectious agent, responsible for an estimated 36.9% of the over 2.2 million infection-associated cancers diagnosed in 2018, more even than those attributed to human papillomavirus (31.5%), or the Hepatitis B and C viruses combined (23.5%). Currently, however, little is known about whether the disparity in gastric cancer is a result of differences in H. pylori prevalence, host response to H. pylori, or differences in other risk factors that might affect the development of gastric cancer. These potential other risk factors include key individual and neighborhood characteristics that differ greatly by race, such as household crowding and residential segregation, which could increase the risk of H. pylori infection, contribute to chronic stress, and induce a more severe immune response. Our goal is to fill the gap in knowledge of risk factors for H. pylori- associated gastric cancer to provide the understanding of the underlying factors that indicate who is at high risk of gastric cancer in the US. To do this, we will build a nested case-control study of approximately 800 non-cardia gastric cancer cases and 2:1 matched controls, utilizing prospective cohort data from a diverse population in the US (67% non-white) from 4 NCI-funded cohorts with pre-diagnostic specimens available: Multiethnic Cohort Study (MEC); Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO); Southern Community Cohort Study (SCCS); and Women’s Health Initiative (WHI). We will assay these biospecimens for antibody levels to H. pylori-specific proteins and for pepsinogen (a validated marker of gastric atrophy), thoroughly assess individual and neighborhood factors that are associated with gastric cancer risk, and determine what drives the differences in race by H. pylori antibody levels and atrophy and resulting gastric cancer risk. Finally, we will develop an integrated “cells to society” modeling framework to assess the impact of social determinants of health on the patterns of H. pylori antibody levels, gastric atrophy and resulting disparities in gastric cancer. Ultimately, these findings will provide the information needed to allow for targeting of high-risk patients for the clinical trials necessary to create screening guidelines for the prevention and early detection of gastric cancer in the US, and will help clinicians with precision prevention by laying the groundwork for the building of a risk prediction tool.

摘要 在美国，胃癌的负担不成比例地落在种族/少数民族身上，发病率为 黑人、亚裔和西班牙裔美国人的比例是非西班牙裔白人的两到三倍。此外，那些自我-- 确定属于这三个群体中的任何一个也更有可能死于胃癌，并比较布莱克 具体地说，男性对白人男性的死亡率差距比所有其他癌症的死亡率差距更大。在美国，胃癌 存活率特别低(5年时为32%)，因为它通常直到晚期才出现症状，此时不接受治疗。 效果更好。在美国，每年有26,000人被诊断为胃癌，超过10,000人死于 疾病。此外，随着时间的推移，胃癌的种族差异继续扩大。然而，潜在的原因是 在美国，人们对胃癌发病率的种族差异研究得还很少。胃病的主要病因 癌症是感染了常见的幽门螺杆菌(H.Pylori)。幽门螺杆菌在人群中更为普遍 事实上，幽门螺杆菌是世界上唯一领先的致癌感染物， 在2018年诊断出的220多万感染相关癌症中，估计有36.9%是罪魁祸首，甚至更多 比被认为是人类乳头瘤病毒(31.5%)或乙肝和丙型肝炎病毒(23.5%)的病例更多。目前， 然而，关于胃癌的差异是否是幽门螺杆菌感染率、宿主的差异所致，我们知之甚少。 对幽门螺杆菌的反应，或其他可能影响胃癌发展的危险因素的差异。这些 潜在的其他风险因素包括关键的个人和邻居特征，这些特征因种族而有很大差异，例如 家庭拥挤和居住隔离可能会增加感染幽门螺杆菌的风险，导致慢性幽门螺杆菌 压力，并诱导更严重的免疫反应。我们的目标是填补幽门螺杆菌风险因素知识的空白- 相关胃癌提供对潜在因素的了解，这些因素表明谁是胃癌的高危人群 癌症在美国。为此，我们将对大约800例非贲门癌病例进行嵌套式病例对照研究。 2：1配对对照，使用来自美国不同人群(67%非白人)的前瞻性队列数据，从4 提供诊断前样本的NCI资助的队列：多民族队列研究(MEC)；前列腺、肺、结直、 和卵巢癌筛查试验(PLCO)；南方社区队列研究(SCCS)；妇女健康倡议 (WHI)。我们将检测这些生物样品对幽门螺杆菌特异性蛋白的抗体水平和胃蛋白酶原(一种经过验证的 胃萎缩的标志物)，彻底评估与胃癌相关的个体和邻近因素 风险，并通过幽门螺杆菌抗体水平和萎缩以及由此导致的胃癌来确定导致种族差异的原因 风险。最后，我们将开发一个集成的“细胞到社会”的建模框架，以评估社会 幽门螺杆菌抗体水平、胃萎缩和由此导致的胃部差异的健康决定因素 癌症。最终，这些发现将提供所需的信息，以便为高危患者提供 为美国预防和早期发现胃癌制定筛查指南所需的临床试验， 并将通过为建立风险预测工具奠定基础，帮助临床医生进行精准预防。