Helicobacter pylori blood biomarker for gastric cancer risk in East Asia

描述(申请人提供)：胃癌是世界上第二致命的癌症，发病率和死亡率在东亚最高。幽门螺杆菌感染是已知的最大的胃癌风险因素，也是整个东亚的地方病，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的遗传变异水平很高，因此有可能识别出能够将幽门螺杆菌感染者分为高风险组和低风险组的风险标记，这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，因为根除幽门螺杆菌被发现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记物可以被可行地评估，可以估计胃癌风险的显著增加。最近，我们进行了一项嵌套在中国前瞻性队列中的初步研究，以确定潜在的幽门螺杆菌血液生物标记物。利用新的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)血清阳性结果的增加可能是一种新的胃癌风险的生物标志物。我们发现，这个生物标记物组合在区分风险方面明显强于仅有CagA蛋白的证据，导致那些对所有六种指示的幽门螺杆菌蛋白都有抗体的人患幽门螺杆菌感染的风险增加三到五倍。 远端胃癌。将这些结果复制到其他人群中，特别是其他可能被类似亚洲菌株殖民的高rsk东亚人群，将增加利用这些幽门螺杆菌血液生物标记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一个由8个前瞻性队列研究组成的联盟，以确定我们是否可以复制这个新的胃癌风险生物标志物小组。我们的目标是：在东亚2,000例远端胃癌病例和2,000例对照中，评估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系；确定炎症或炎症易感性等宿主因素是否有助于评估胃癌风险；以及建立包括幽门螺杆菌血液生物标志物在内的东亚胃癌风险预测模型，使我们能够将个体分为胃癌高风险组和低风险组，然后在高危人群中同时患有癌症和癌前病变的个体中验证该模型。该项目是对PA-11-158：感染相关癌症的生物标记物(R01)的直接响应，申请者被邀请调查幽门螺杆菌与胃癌的关联，以确定暴露于该病毒的个体中可能患癌症的亚群。如果我们确定并验证一个预测高发人群风险增加的风险预测模型，我们将创造机会，通过在高风险人群中有针对性的预防策略，大幅加强对这种致命癌症的预防，同时也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.