The Oral Microbiome and Upper Aerodigestive Squamous Cell Cancer

我们提出了一项创新研究，以检查口腔微生物群是否与上呼吸道消化鳞状细胞癌（UADSCC：口腔、咽、喉和食管鳞状细胞癌）的风险相关。我们的研究团队已经开发了进行微生物组研究的独特能力（NIH资助：1UH2CA140233, 5R01AI063477），最近报道了前肠微生物组谱与食管恶性前病变的关系（Yang等人，Gastroenterology, 2009），现在有初步数据显示口腔微生物组与口腔癌风险之间存在关联。烟草和酒精是已知的UADSCC的主要危险因素。我们假设口腔内的微生物可能会加剧UADSC的致癌作用，可能与酒精和烟草使用有关。我们研究的目的是将口腔微生物组与UADSCC风险联系起来，并确定酒精和烟草使用对口腔微生物组的影响，这是该主题的第一次流行病学调查。我们计划在140例UADSCC病例和420例对照中，通过对口腔洗液样本中的16S rRNA微生物基因测序来表征所有常见的口腔微生物物种（包括不可培养的微生物）。由于UADSCC疾病和治疗状态可以改变口腔微生物特征（反向因果关系），我们采用前瞻性研究设计，在ACS和PLCO队列中，在疾病发展之前收集口腔洗液样本。我们的研究将确定与UADSCC风险相关的口腔细菌特征，为实施预防性干预提供直接线索，作为预防UADSCC的酒精和烟草控制计划的重要辅助手段。

DESCRIPTION (provided by applicant): The Oral Microbiome and Upper Aerodigestive Squamous Cell Cancer We propose an innovative study to examine whether the oral microbiome is associated with risk of upper aerodigestive squamous cell cancers (UADSCC: oral, pharyngeal, laryngeal and esophageal squamous cell cancers). Our research team has developed a unique capability to conduct microbiome research (NIH grant: 1UH2CA140233, 5R01AI063477), have recently reported the relationship of foregut microbiome profiles with esophageal premalignant conditions (Yang et al., Gastroenterology, 2009), and now have preliminary data showing an association between the oral microbiome and oral cancer risk. Tobacco and alcohol are the major known risk factors for UADSCC. We hypothesize that microorganisms in the oral cavity potentiate UADSC carcinogenesis, potentially related to alcohol and tobacco use. The goals of our study are to relate the oral microbiome to UADSCC risk and to identify the impact of alcohol and tobacco use on the oral microbiome, in the first epidemiologic investigation of this topic. We plan to characterize, in 140 UADSCC cases and 420 controls, all common oral microbial species (including non-culturables) by sequencing the 16S rRNA microbial genes in oral wash samples. Because UADSCC disease and treatment status can alter oral microbial profiles (reverse causation), we are using a prospective research design, in the ACS and PLCO cohorts in which oral wash samples were collected prior to disease development. Our study will identifying oral bacterial profiles related to UADSCC risk, providing direct leads to implement prophylactic interventions as critical adjuncts to alcohol and tobacco control programs in UADSCC prevention.