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: 9464051
• 负责人: MEIRA EPPLEIN
• 金额: $ 41.14万
• 依托单位: DUKE UNIVERSITY
• 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 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9464051
• 关键词: Helicobacter; pylori; blood; biomarker; gastric

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，并且在东亚发病率和死亡率最高。胃癌的最强危险因素感染了幽门螺杆菌，在整个东亚也是流行的，但只有少数受感染的个体发生胃癌。由于幽门螺杆菌分离株之间的遗传差异很高，因此可能可以识别出幽门螺杆菌感染的个体分类为高风险组的风险标记，这为预防成本效益的疾病提供了独特的机会。这尤其重要，因为已发现塔H.孔的消除可有效降低胃癌的发病率。但是，目前，尚无可靠评估的已知生物标志物，可以估计胃癌风险显着增加。最近，我们进行了一项嵌套在中国人群中的试点研究，以鉴定潜在的幽门螺杆菌血液生物标志物。利用新型的幽门螺杆菌多重血清学，我们发现，增加的血清阳性结果增加到六种幽门螺杆菌蛋白（OMP，HP0305，HYUA，HPAA，HPAA，CAGA和VACA）可能是胃癌风险的新生物标志物。我们发现，该生物标志物面板在区分风险方面比单独的CAGA蛋白的证据要强得多，从而导致那些对所有六个具有抗体的个体，表明幽门螺杆菌蛋白的风险增加了三到五倍。 胃癌远端。在其他种群中复制这些结果，尤其是可能被类似亚洲菌株殖民的其他高RSK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，我们已经在中国，日本和韩国的高胃癌患者种群中组成了八项前瞻性队列研究，以确定我们是否可以复制这个新型的胃癌风险生物标志物小组。我们的目的是：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在东亚2,000例胃癌风险和2,000例对照中的关联；确定炎症的宿主因素是否有助于评估胃癌风险；并建立一个包括幽门螺杆菌血液生物标志物在内的东亚胃癌风险的预测模型，使我们能够将个体分为胃癌的高风险组，然后在高风险人群中验证癌症和预癌性病变的个体中的这种模型。该项目是在直接响应PA-11-158的直接反应：与感染相关癌症的生物标志物（R01），邀请申请人调查幽门螺杆菌和胃癌的关联，以识别可能患有癌症的暴露个人的亚群。”如果我们确定并验证一种预测高处率人群风险增加的风险预测模型，我们将通过针对最高风险的幽门螺杆菌感染的个体中有针对性的预防策略来实质性地预防这种致命的癌症，同时还减少了低风险的不必要的抗生素使用。