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: 10685530
• 负责人: MEIRA EPPLEIN
• 金额: $ 62.79万
• 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/10685530
• 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; Disparity; Far East; Funding; Future; Genes; Goals; Helicobacter Infections; Helicobacter pylori; Helicobacter pylori induced gastric cancer; Hepatitis B Virus; Hepatitis C virus; Hispanic Populations; Household; Human Papillomavirus; 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; 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; biomarker validation; 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; outcome disparities; people of color; predictive tools; premalignant; racial difference; racial disparity; racial minority; residential segregation; risk prediction; screening guidelines; social health determinants

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.

抽象的 胃癌的伯宁因种族/族裔少数群体而不成比例，发病率 在非西班牙裔白人中，黑人，亚洲人和西班牙裔二到三倍。此外，那些自我的个人 确定属于这三组中的任何一组也更有可能死于胃癌，并比较黑 对白人的人，特别是，这种死亡率差异大于所有其他癌症的死亡率差异。在美国，胃癌 由于治疗无效，直到晚期，其生存率特别低（5年为32％），因为它通常是不对称的 更长的有效。每年在美国，有26,000人被诊断出患有胃癌，超过10,000人死亡 疾病。此外，随着时间的流逝，胃癌的种族差异持续增长。然而，出现的根本原因 在美国，胃癌发病率的这种种族差异已被基本了解。胃的主要原因 癌症是常见细菌，幽门螺杆菌（H. Pylori）感染。幽门螺杆菌在人们中更为普遍 颜色比非西班牙裔白人，实际上，幽门螺杆菌是世界上单一领先的致癌剂， 负责2018年被诊断出的220万次与感染相关的癌症中估计有36.9％ 比归因于人乳头瘤病毒（31.5％）或丙型肝炎病毒（23.5％）的那些。现在， 但是，关于胃癌的差异是否是幽门螺杆菌患病率差异的结果，宿主的差异知之甚少。 对幽门螺杆菌的反应，或可能影响胃癌发展的其他风险因素的差异。这些 潜在的其他风险因素包括关键的个人和社区特征，这些特征是不同的，例如 家庭拥挤和居民种族隔离可能会增加幽门螺杆菌感染的风险 压力，并引起更严重的免疫响应。我们的目标是填补幽门螺杆菌风险因素的知识的空白 相关的胃癌，以提供对表明谁处于胃的高风险的潜在因素的理解 在美国的癌症。为此，我们将对大约800个非心脏胃癌病例进行嵌套的病例对照研究 和2：1匹配的对照，使用来自美国潜水员人群的前瞻性队列数据（67％的非白人） NCI资助的队列具有诊断前标本可用的：多民族队列研究（MEC）；前列腺，肺，结直肠肠， 和卵巢癌筛查试验（PLCO）；南方社区队列研究（SCCS）；和妇女健康计划 （whi）。我们将对幽门螺杆菌特异性蛋白的抗体水平和胃蛋白酶原（经过验证）主张这些生物测量。 胃萎缩的标记），彻底评估与胃癌相关的个体和邻里因素 风险，并确定是什么推动了幽门螺杆菌抗体水平和萎缩和胃癌的种族差异 风险。最后，我们将开发一个综合的“社会牢房”建模框架来评估社会的影响 健康的决定因素在幽门螺杆菌抗体水平，胃萎缩和胃的分布的模式下 癌症。最终，这些发现将提供允许针对高风险患者的信息 为了制定预防和早期检测胃癌的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来帮助临床医生进行精确预防。