Microbial Surrogate Assay for Environmental PAH Exposure

描述（由申请人提供）：Arphion是一家开发非侵入性产品的公司，该产品将用于诊断，预防和治疗头颈部和其他癌症。美国每年有41，000人被诊断患有头颈癌（HNC），其中8，000人死亡。由于暴露于烟草和某些食物中发现的多环芳烃（PAH），美国数千万人面临HNC的风险增加。其他风险因素也涉及其中，因为尽管美国有数百万人暴露于高水平的烟草多环芳烃和第二个风险因素乙醇，但只有少数人会患上这种疾病。奇怪的是，烟草引起的牙周病发生的口腔细菌的变化不知何故也增加了HNC的风险。Joel Schwartz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。他们表明，烟草使用者有过量的8种不同的口腔微生物物种可以代谢多环芳烃，并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，在口腔粘膜中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计划表明8BAC与人类粘膜DNA加合物的形成有关，并且基于快速PCR/DNA测序的患者口腔中8BAC微生物的测量将与DNA加合物水平相关。Arphion的产品将检测到细胞DNA中DNA加合物的替代物8BAC水平升高，这是困难和昂贵的测量。建议具有高水平8BAC的HNC高风险患者改变烟草消费，并每半年进行一次头颈癌检查。该I期研究的第二个目标是通过显示8BAC在患有这种疾病的患者中相对于无HNC的匹配受试者升高来显示8BAC微生物和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最有可能进入HNC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，在第二阶段成功验证8BAC水平和粘膜DNA加合物水平之间的联系之后，与一家在自动DNA分离和分析方面有经验的大公司合作，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，然后牙科医生将保存的样本送到Arphion进行收费测试分析。

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.