Helicobacter pylori protein-specific antibodies and colorectal cancer risk

幽门螺杆菌蛋白特异性抗体与结直肠癌风险

• 批准号: 8894172
• 负责人: MEIRA EPPLEIN
• 金额: $ 67.42万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2016-04-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8894172
• 关键词: Accounting; African American; Age; Age-Years; Antibiotics; Antibodies; Aspirin; Bacteria; Biological Markers; Blood; Cancer Prevention Study II; Carcinogens; Chronic; Cohort Studies; Collection; Colon; Colon Carcinoma; Colorectal; Colorectal Cancer; Communities; Community Health Centers; Cytotoxin; Death Rate; Developing Countries; Diagnosis; Disease; Distant; Dose; Epidemiologic Studies; Evaluation; Examinations and Diagnoses; Exposure to; Future; Gastric mucosa; Health; Health Professional; Helicobacter Infections; Helicobacter pylori; High Prevalence; Histologic; Human; Incidence; Individual; Infection; Inflammation; Life; Literature; Low income; Lung; Malignant Neoplasms; Meta-Analysis; Modification; Nested Case-Control Study; Nurses' Health Study; Outcome; Ovarian; Participant; Persons; Physicians; Population; Prevalence; Prevention; Prevention strategy; Prospective Studies; Prostate; Proteins; Proton Pump Inhibitors; Public Health; Recruitment Activity; Regimen; Reporting; Research; Risk; Risk Factors; Serologic tests; Seroprevalences; Site; Southeastern United States; Staging; Stomach; Stroke; Surveys; Time; Uninsured; Variant; Virulence Factors; Virulent; Woman; Women' s Health; Work; base; cancer diagnosis; cancer prevention; cancer risk; case control; colorectal cancer prevention; cost effective; design; experience; follow-up; interest; malignant stomach neoplasm; men; novel; prospective; protective effect; public health relevance; racial disparity; response; screening

 DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is the third most common and third most deadly cancer in the US. Current evidence suggests that CRC incidence is increasing among both men and women younger than 50 years of age, who are also more likely to be diagnosed with late-stage disease. Additionally, there is a significant racial disparity, in that African American men and women experience a higher incidence of colorectal cancer compared to white men and women, and an even higher rate of death from colorectal cancer compared to the white population. Recent studies suggest that infection with Helicobacter pylori, a known gastric-cancer carcinogen, may also increase the risk of CRC, although these findings have been inconsistent. Two recent meta-analyses found statistically significant 40% to 50% increased odds for CRC among H. pylori-positive individuals. However, the majority of the studies surveyed did not take into account the H. pylori sub-type. It is known that, as H. pylori has evolved over 50,000 years to live in the human stomach, the bacteria have become highly diverse genetically. The proposed project builds on our work in the Southern Community Cohort Study, in which we found a statistically significant 60-80% increase in the odds of CRC for individuals sero-positive for one of five specific H. pylori proteins. For colon cancer alone, thes associations were stronger, so that sero- positivity to any of these five proteins was associated with a significant, approximate two-fold increased risk, most prominently for the known H. pylori virulence factor VacA (OR for VacA sero-positivity, 2.24). The association of VacA sero-positivity was particularly strong for CRC that has distant spread (OR, 5.67), among younger (<55 y) individuals (OR, 3.48), and for cancer of the right colon (OR, 3.13). Furthermore, a strong, significant, positive dose-response association across increasing quartiles of VacA antibody level was also observed. The current project seeks to produce the most definitive study to date of the H. pylori-CRC association through evaluation of the association in a large, collaborative nested case-control study (including over 4,000 prospectively-ascertained cases from 10 cohort studies spanning the US, and 1:1 matched controls), assessment of differences in the association by time from blood collection to diagnosis, and examination of the potential interaction of regular aspirin use on the association of H. pylori protein-specific infection with CRC risk. Thus, the current project allows us to thoroughly evaluate the novel association between Helicobacter pylori protein-specific infection and CRC risk, particularly for aggressive disease, building the groundwork for significantly strengthening CRC prevention and screening strategies with a new risk biomarker. Furthermore, this project provides the opportunity to potentially identify an infectious exposure to a common cancer that may be modifiable by a regimen of regular aspirin use, and moreover has already been proven to be modifiable through the use of H. pylori-eradication therapy and, thus, possibly holds great promise as a CRC prevention strategy.

 描述（由申请人提供）：结直肠癌（CRC）是美国第三常见和第三致命的癌症。目前的证据表明，CRC的发病率在50岁以下的男性和女性中都在增加，他们也更有可能被诊断为晚期疾病。此外，存在显著的种族差异，因为与白色男性和女性相比，非裔美国男性和女性经历更高的结肠直肠癌发病率，并且与白色人群相比，甚至更高的结肠直肠癌死亡率。最近的研究表明，感染幽门螺杆菌，一种已知的胃癌致癌物，也可能增加CRC的风险，尽管这些研究结果一直不一致。最近的两项荟萃分析发现，在H. pylori阳性个体。然而，大多数调查的研究没有考虑到H。pylori亚型。据了解，H.幽门螺杆菌已经进化了5万年，在人类的胃里生存，这种细菌在遗传上已经变得高度多样化。拟议的项目建立在我们在南方社区队列研究中的工作基础上，在该研究中，我们发现五种特定H. pylori蛋白对于单独的结肠癌，这些关联更强，因此对这五种蛋白质中的任何一种的血清阳性都与显著的、大约两倍的风险增加相关，最突出的是已知的H. pylori毒力因子VacA（VacA血清阳性的OR为2.24）。VacA血清阳性与远处转移的CRC（OR，5.67）、年轻（<55岁）个体（OR，3.48）和右半结肠癌（OR，3.13）的相关性特别强。此外，还观察到VacA抗体水平增加的四分位数之间存在强烈的、显著的、阳性剂量反应相关性。目前的项目旨在产生迄今为止对H.通过一项大型协作巢式病例对照研究（包括来自美国10项队列研究的4，000多例前瞻性确定的病例，以及1：1匹配的对照）评估幽门螺杆菌与CRC的相关性，评估从血液收集到诊断的时间之间的相关性差异，并检查定期使用阿司匹林对H. pylori蛋白特异性感染与CRC风险。因此，目前的项目使我们能够彻底评估幽门螺杆菌蛋白特异性感染与CRC风险之间的新关联，特别是对于侵袭性疾病，为显着加强CRC预防和筛查策略奠定基础。此外，该项目提供了可能识别常见癌症的感染性暴露的机会，该常见癌症可以通过定期使用阿司匹林的方案来改变，并且已经证明可以通过使用H.因此，作为CRC预防策略，可能具有很大的前景。