Helicobacter pylori blood biomarker for gastric cancer risk in East Asia

描述（申请人提供）：胃癌是世界上第二大致命的癌症，东亚地区的发病率和死亡率最高。幽门螺杆菌感染是目前已知的导致胃癌的最强危险因素，也是东亚地区的一种地方性疾病，但只有一小部分感染者最终发展为胃癌。由于幽门螺杆菌分离株之间的遗传变异水平很高，因此有可能确定风险标记，将幽门螺杆菌感染个体分为高风险和低风险组，为经济有效的疾病预防提供了独特的机会。这一点尤其重要，因为已经发现根除幽门螺杆菌可以有效地降低胃癌的发病率。然而，目前还没有一种已知的生物标志物可以评估胃癌风险的显著增加。最近，我们在中国前瞻性队列中进行了一项初步研究，以确定潜在的幽门螺杆菌血液生物标志物。利用新的幽门螺杆菌多重血清学，我们发现6种幽门螺杆菌蛋白（Omp、HP0305、HyuA、HpaA、CagA和VacA）血清阳性结果的增加可能是胃癌风险的一种新的生物标志物。我们发现该生物标志物组在鉴别风险方面明显强于单独的CagA蛋白证据，导致那些具有所有六种指示幽门螺杆菌蛋白抗体的个体的风险增加了三到五倍

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.