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

摘要 胃癌的负担福尔斯不成比例地落在美国的种族/少数民族身上， 黑人、亚洲人和西班牙裔人比非西班牙裔白人高出两到三倍。此外，自我- 被鉴定为属于这三个群体中任何一个的人也更有可能死于胃癌， 具体而言，男性与白色男性之间的死亡率差异大于所有其他癌症。在美国，胃癌 有一个特别低的生存率（32%，在5年），因为它通常是无症状的，直到晚期，当治疗是不 更有效。在美国，每年有26，000人被诊断患有胃癌，并且超过10，000人死于胃癌。 疾病此外，随着时间的推移，胃癌的种族差异继续扩大。然而， 在美国，胃癌发病率的种族差异基本上没有得到充分研究。胃溃疡的主要原因 癌症是感染了常见的细菌，幽门螺杆菌（H。pylori）。H.幽门螺杆菌在人类中更为普遍， 比非西班牙裔白人，事实上，H。幽门螺杆菌是世界上唯一的主要致癌传染因子， 在2018年诊断出的220多万感染相关癌症中，估计有36.9%是由它引起的，甚至更多。 高于人乳头瘤病毒（31.5%）或B和C型肝炎病毒（23.5%）。目前， 然而，关于胃癌中的差异是否是H.幽门螺杆菌患病率，宿主 响应H。幽门螺杆菌，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社区特征，这些特征因种族而有很大差异，例如 家庭拥挤和居住隔离，这可能会增加H。幽门螺杆菌感染，有助于慢性 压力，并诱导更严重的免疫反应。我们的目标是填补对H.幽门- 相关的胃癌，以提供对潜在因素的理解，表明谁是胃癌的高风险， 癌症在美国为此，我们将建立一个巢式病例对照研究约800例非贲门胃癌病例 和2：1匹配的对照，利用来自美国不同人群（67%非白人）的前瞻性队列数据， 具有可用诊断前标本的NCI资助的队列：多种族队列研究（MEC）;前列腺、肺、结直肠、 卵巢癌筛查试验（PLCO）;南方社区队列研究（SCCS）;和妇女健康倡议 （WHI）。我们将检测这些生物样本的H抗体水平。幽门特异性蛋白质和胃蛋白酶原（一种经验证的 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，并确定是什么驱动了种族的差异。幽门螺杆菌抗体水平与萎缩及由此导致的胃癌 风险最后，我们将开发一个综合的“细胞到社会”建模框架，以评估社会的影响， 健康决定因素对H.幽门螺杆菌抗体水平，胃萎缩和导致的差异，胃 癌最终，这些发现将提供所需的信息，以便针对高风险患者进行治疗。 在美国进行必要的临床试验，以制定预防和早期发现胃癌的筛查指南， 并将通过为风险预测工具的构建奠定基础来帮助临床医生进行精确预防。

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.