Microbial Surrogate Assay for Environmental PAH Exposure

环境 PAH 暴露的微生物替代测定

• 批准号: 8715044
• 负责人: Guy Richard Adami
• 金额: $ 14.85万
• 依托单位: ARPHION, LTD
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8715044
• 关键词: Behavior Therapy; Biological Assay; Carcinogen exposure; Carcinogens; Cells; Cessation of life; DNA; DNA Adduction; DNA Adducts; DNA Sequence; DNA analysis; Dental; Dentists; Diagnosis; Diagnostic; Disease; Enzymes; Ethanol; Exposure to; Fees; Food; Goals; Head and Neck Cancer; Head and neck structure; Health; Human; Knowledge; Link; Malignant Neoplasms; Mass Spectrum Analysis; Measurement; Measures; Mediating; Metabolism; Methods; Microbe; Minority; Mutagens; Neck Cancer; Oral; Oral cavity; Oral mucous membrane structure; Patients; Periodontal Diseases; Phase; Play; Population; Reporting; Research; Risk; Risk Assessment; Risk Factors; Role; Sampling; Services; Small Business Technology Transfer Research; Smoker; Staging; Swab; Testing; Tobacco; Tobacco smoke; Tobacco use; United States; Work; aryl hydrocarbons; base; cancer prevention; cancer risk; clinical research site; commercial application; experience; head and neck cancer patient; head and neck cancer prevention; high risk; improved; innovation; malignant mouth neoplasm; microbial; oral bacteria; oral microbiome; prevent; tool

DESCRIPTION (provided by applicant): Arphion is a company established to develop noninvasive products that will be used to diagnose, prevent, and treat head and neck and other cancers. 41,000 people are diagnosed with head and neck cancer (HNC) every year in the United States, with 8,000 deaths. Tens of millions of people in the US are at increased risk for HNC due to exposure to the polycyclic aryl hydrocarbons (PAHs) found in tobacco and some foods. Other risk factors are involved, because although many millions of people in the US are exposed to high levels of tobacco PAHs and a second risk factor, ethanol, only a small minority will get the disease. Curiously, the changes in oral bacteria that occur with tobacco-induced periodontal disease somehow also increase the risk for HNC. Dr. Joel Schwartz's team has recent evidence that may explain the connection between oral bacteria and cancer. They showed that tobacco users have excess numbers of 8 different oral microbial species that can metabolize PAHs, and that the metabolism can increase reactivity of these molecules. We hypothesis that these microbes, which we refer to as 8BAC, play a major role in DNA adduct formation in the oral mucosa, a key early step in formation of most HNC. Arphion plans to show that 8BAC is linked to mucosal DNA adduct formation in humans and that rapid PCR/DNA sequencing based measurement of 8BAC microbes in a patient's mouth will correlate to DNA adduct levels. Arphion's product would detect elevated levels of 8BAC as a surrogate for DNA adducts in cellular DNA, which are difficult and expensive to measure. Patients at high risk for HNC with high levels of 8BAC would be advised to change their tobacco consumption, and to have semiannual head and neck cancer exams. A second goal of this Phase I research is to show a firm link between 8BAC microbes and HNC by showing 8BAC is elevated in patients with this disease versus matched subjects who are HNC- free. Arphion's product will identify among smokers, and others with high carcinogen exposure, those most likely to go on to HNC. This will provide true cancer prevention by facilitating behavior modification. Our plan, after a successful Phase II, where we verify the link between 8BAC levels and mucosal DNA adduct levels, is to partner with a large firm with experience with automated DNA isolation and analysis, and knowledge of FDA regulatory requirements so we can begin providing kits to dental practitioners who will then send preserved samples to Arphion for analysis on a fee-for-test basis.

简介（由申请人提供）：Arphion是一家开发用于诊断、预防和治疗头颈部和其他癌症的非侵入性产品的公司。在美国，每年有4.1万人被诊断出患有头颈癌（HNC），其中8000人死亡。由于接触烟草和一些食物中发现的多环芳烃（PAHs），美国数千万人患HNC的风险增加。其他风险因素也参与其中，因为尽管美国有数百万人暴露在高水平的烟草多环芳烃和第二个风险因素乙醇中，但只有一小部分人会患上这种疾病。奇怪的是，发生在烟草引起的牙周病的口腔细菌的变化在某种程度上也增加了HNC的风险。乔尔·施瓦茨博士的团队最近有证据可以解释口腔细菌和癌症之间的联系。他们发现，烟草使用者体内有过量的8种不同的口腔微生物，这些微生物可以代谢多环芳烃，而且代谢可以增加这些分子的反应性。我们假设这些微生物，我们称之为8BAC，在口腔黏膜DNA加合物的形成中起主要作用，这是大多数HNC形成的关键早期步骤。Arphion计划证明8BAC与人类粘膜DNA加合物的形成有关，并且基于患者口腔中8BAC微生物的快速PCR/DNA测序测量将与DNA加合物水平相关。Arphion的产品将检测细胞DNA中DNA加合物的8BAC水平升高，而DNA加合物的测量既困难又昂贵。高8BAC水平的HNC高危患者应改变烟草消费，并每半年进行一次头颈癌检查。这项I期研究的第二个目标是通过显示患有这种疾病的患者与没有HNC的匹配受试者的8BAC升高来显示8BAC微生物与HNC之间的牢固联系。Arphion的产品将在吸烟者和其他高致癌物暴露者中识别出那些最有可能患上高致癌物质的人。这将通过促进行为改变来提供真正的癌症预防。我们的计划是，在第二期成功验证8BAC水平与粘膜DNA加合物水平之间的联系后，我们将与一家具有自动化DNA分离和分析经验的大公司合作，并了解FDA的监管要求，这样我们就可以开始向牙科医生提供试剂盒，他们将保存的样品送到Arphion进行分析，并收取测试费用。

项目成果

Enrichment of polycyclic aromatic hydrocarbon metabolizing microorganisms on the oral mucosa of tobacco users.

• DOI: 10.7717/peerj.16626
• 发表时间: 2024
• 期刊: PeerJ
• 影响因子: 2.7
• 作者: Tao L;Chiarelli MP;Pavlova S;Kolokythas A;Schwartz J;DeFrancesco J;Salameh B;Green SJ;Adami G
• 通讯作者: Adami G