Helicobacter pylori blood biomarker for gastric cancer risk in East Asia

描述（由申请人提供）：胃癌是世界上第二大致命癌症，东亚的发病率和死亡率最高。幽门螺杆菌感染是已知的胃癌最强的危险因素，也是东亚的地方病，但只有一小部分感染者会发展成胃癌。由于H. pylori分离株，有可能鉴定出可将H.将幽门螺杆菌感染者分为高风险和低风险群体，为具有成本效益的疾病预防提供了独特的机会。这一点尤其重要，因为H。已经发现根除幽门可以有效地降低胃癌的发病率。然而，目前还没有已知的生物标志物可以进行可行的评估，可以估计胃癌风险的显著增加。最近，我们在一个前瞻性的中国队列中进行了一项初步研究，以确定潜在的H。幽门螺杆菌血液生物标志物。利用H. pylori多重血清学，我们发现血清学阳性结果增加到6个H。pylori蛋白（Omp、HP 0305、HyuA、HpaA、CagA和VacA）可能是胃癌风险的新生物标志物组。我们已经发现，这种生物标志物组在识别风险方面比单独的CagA蛋白证据明显更强，导致那些对所有六种指示H.幽门螺杆菌蛋白质具有三至五倍的风险增加， 远端胃癌这些结果在其他人群中的复制，特别是其他可能被类似亚洲菌株定殖的高rsk东亚人群，将增加利用这些H.幽门螺杆菌血液生物标志物用于胃癌筛查。因此，我们在中国、日本和韩国的高胃癌发病率人群中进行了8项前瞻性队列研究，以确定我们是否可以复制这种新的胃癌风险生物标志物。我们的目标是：评估H。在东亚2，000例远端胃癌病例和2，000例对照中，具有胃癌风险的诊断前血液样本中的幽门螺杆菌蛋白抗体水平;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;并建立东亚胃癌风险的预测模型，包括H. pylori血液生物标志物，使我们能够将个体分为胃癌的高风险组和低风险组，然后在高风险人群中的癌症和癌前病变个体中验证该模型。该项目是直接响应PA-11-158：预防相关癌症的生物标志物（R 01）而提出的，该项目邀请申请人调查H。幽门螺杆菌和胃癌“，以确定可能患癌症的接触者亚群。“如果我们确定并验证一个风险预测模型，预测高发病率人群的风险增加，我们将创造机会，通过有针对性的预防策略，在H。这将有助于减少高危人群中幽门螺杆菌感染者的不必要抗生素使用，同时减少低风险人群中不必要的抗生素使用。

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.