Helicobacter pylori blood biomarker for gastric cancer risk in East Asia

东亚胃癌风险的幽门螺杆菌血液生物标志物

• 批准号: 9091479
• 负责人: MEIRA EPPLEIN
• 金额: $ 44.36万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9091479
• 关键词: Age; Antibiotics; Antibodies; Asians; Atrophic Gastritis; Biological Markers; Blood; Blood specimen; China; Chinese People; Cohort Studies; Development; Diagnosis; Diagnostic; Disease; Distal; Enrollment; Etiology; Far East; Genetic Variation; Grant; Health; Helicobacter pylori; Incidence; Individual; Infection; Inflammation; Integration Host Factors; Japan; Korea; Lead; Lesion; Malignant Neoplasms; Measures; Modeling; Morbidity - disease rate; Nested Case-Control Study; PTGS2 gene; Pathway interactions; Pepsinogen A; Pilot Projects; Population; Predictive Value; Predisposition; Premalignant; Prevention; Prevention strategy; Proteins; Risk; Risk Factors; Risk Marker; Role; Screening for Gastric Cancer; Serologic tests; Virulence Factors; biomarker panel; cancer risk; cohort; cost effective; disorder prevention; gastric cancer prevention; high risk; improved; male health; malignant stomach neoplasm; men; molecular marker; mortality; new technology; novel; novel marker; predictive modeling; prospective; response; sex; tool; urinary

DESCRIPTION (provided by applicant): Gastric cancer is the second most deadly cancer in the world, and incidence and mortality rates are highest in East Asia. Infection with Helicobacter pylori, the strongest known risk factor for gastric cancer, is also endemic throughout East Asia, but only a small percentage of infected individuals ever develop gastric cancer. Due to the high level of genetic variation among H. pylori isolates, it may be possible to identify risk markers tht could classify H. pylori-infected individuals into high- and low-risk groups, presenting a unique opportunity for cost- effective disease prevention. This is especially significant because H. pylor eradication has been found to effectively reduce gastric cancer incidence. Currently, however, there is no known biomarker that is feasibly assessed that can estimate a substantially significant increase in risk for gastric cancer. Recently, we performed a pilot study nested in a prospective Chinese cohort to identify potential H. pylori blood biomarkers. Utilizing novel H. pylori multiplex serology, we found that increasing number of sero-positive results to six H. pylori proteins (Omp, HP0305, HyuA, HpaA, CagA, and VacA) may be a novel biomarker panel for gastric cancer risk. We have found that this biomarker panel is significantly stronger at discriminating risk than evidence of the CagA protein alone, resulting in those individuals with antibodies to all six indicated H. pylori proteins having a three- to five-fold increase in risk of distal gastric cancer. Replication of these results in other populations, particularly other high-rsk East Asian populations who may be colonized by similar Asian strains, would enhance the possibility of utilizing these H. pylori blood biomarkers for gastric cancer screening. Thus, we have assembled a consortium of eight prospective cohort studies in the high gastric cancer-incidence populations of China, Japan, and Korea, to determine if we can replicate this novel biomarker panel for gastric cancer risk. We aim to: assess the association of H. pylori protein antibody levels in pre-diagnostic blood samples with gastric cancer risk in 2,000 distal gastric cancer cases and 2,000 controls in East Asia; determine if host factors of inflammation or susceptibility to inflammation aid in assessing gastric cancer risk; and build a predictive model for gastric cancer risk in East Asia that includes H. pylori blood biomarkers and enables us to categorize individuals into high and low-risk groups for gastric cancer, and then validate this model among individuals with both cancer and precancerous lesions in a high-risk population. This project is proposed in direct response to PA-11-158: Biomarkers of Infection-Associated Cancers (R01), for which applicants were invited to investigate the association of H. pylori and gastric cancer "to identify subpopulations of exposed individuals who are likely to develop cancer." Should we ascertain and validate a risk prediction model that predicts increased risk in high-incidence populations, we will create the opportunity to substantially increase prevention of this deadly cancer through targeted prevention strategies among H. pylori-infected individuals at highest risk, while also reducing unnecessary antibiotic use among those at low risk.

描述（由申请人提供）：胃癌是世界上第二大致命癌症，发病率和死亡率在东亚地区最高。幽门螺杆菌感染是已知的最强的胃癌危险因素，在整个东亚地区也很流行，但只有一小部分感染者会患上胃癌。由于幽门螺杆菌分离株之间存在高水平的遗传变异，因此有可能识别出风险标记，将幽门螺杆菌感染的个体分为高风险组和低风险组，从而为具有成本效益的疾病预防提供了独特的机会。这尤其重要，因为根除幽门螺杆菌已被发现可以有效降低胃癌的发病率。然而，目前还没有经过可行评估的已知生物标志物可以估计胃癌风险的显着增加。最近，我们在中国前瞻性队列中进行了一项试点研究，以确定潜在的幽门螺杆菌血液生物标志物。利用新型幽门螺杆菌多重血清学，我们发现六种幽门螺杆菌蛋白（Omp、HP0305、HyuA、HpaA、CagA 和 VacA）血清阳性结果数量的增加可能是胃癌风险的新型生物标志物组。我们发现，该生物标志物组在区分风险方面比单独使用 CagA 蛋白的证据明显更强，导致那些对所有六种指定幽门螺杆菌蛋白均具有抗体的个体，其患幽门螺杆菌感染的风险增加了三到五倍。 远端胃癌。在其他人群中复制这些结果，特别是可能被类似亚洲菌株定植的其他高风险东亚人群，将增强利用这些幽门螺杆菌血液生物标志物进行胃癌筛查的可能性。因此，我们在中国、日本和韩国的胃癌高发人群中组建了八项前瞻性队列研究，以确定我们是否可以复制这种新型胃癌风险生物标志物组。我们的目标是：评估东亚地区 2,000 名远端胃癌病例和 2,000 名对照者的诊断前血液样本中幽门螺杆菌蛋白抗体水平与胃癌风险的关联；确定炎症或炎症易感性的宿主因素是否有助于评估胃癌风险；建立东亚地区胃癌风险的预测模型，其中包括幽门螺杆菌血液生物标志物，使我们能够将个体分为胃癌高风险组和低风险组，然后在高风险人群中同时患有癌症和癌前病变的个体中验证该模型。该项目的提出是为了直接响应 PA-11-158：感染相关癌症的生物标志物 (R01)，该项目邀请申请人调查幽门螺杆菌与胃癌的关联，“以确定可能患癌症的暴露个体的亚群”。如果我们确定并验证一个预测高发病人群风险增加的风险预测模型，我们将创造机会，通过对高风险幽门螺杆菌感染者采取有针对性的预防策略，大幅加强对这种致命癌症的预防，同时减少低风险人群不必要的抗生素使用。