Flavonoids, esophageal/gastric cardia adenocarcinoma and Barretts Esophagus Risk

类黄酮、食管/贲门腺癌和 Barretts 食管风险

• 批准号: 8243446
• 负责人: MARILIE D. GAMMON
• 金额: $ 7.22万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8243446
• 关键词: Accounting; Address; Adverse effects; Ancillary Study; Anthocyanidin; Anti-Inflammatory Agents; Anti-inflammatory; Apoptosis; Aspirin; Barrett Esophagus; Beverages; Case-Control Studies; Cell Cycle; Chronic; Clinical; Connecticut; Consumption; Country; Cyclin D1; Data; Databases; Development; Diet; Dietary intake; Epidemiologic Studies; Esophageal; Esophageal Adenocarcinoma; Esophagogastric Junction; Esophagus; Event; Flavanones; Flavones; Flavonoids; Flavonols; Food; Frequencies; Gastric Adenocarcinoma; Gastric Cardia Adenocarcinoma; Gastroesophageal reflux disease; Genetic Transcription; Incidence; Individual; Intake; Isoflavones; Laboratory Study; Length; Link; Malignant Neoplasms; Mucous Membrane; New Jersey; PTGS2 gene; Parents; Pathologic; Pharmaceutical Preparations; Plants; Questionnaires; Reporting; Risk; Risk Reduction; Staging; Subgroup; Tumor Markers; Tumor Subtype; Ulcer; United States; Washington; flavan-3-ol; fruits and vegetables; inhibitor/antagonist; interest; outcome forecast; population based; prevent; research study; tumor

DESCRIPTION (provided by applicant): Flavonoids, esophageal/gastric cardia adenocarcinoma and Barrett's esophagus risk ABSTRACT. The incidence of esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) has increased more rapidly than any other cancer in the United States and other Western countries over the past 30-40 years. EA and GCA appear to develop from normal mucosal lining through a sequence of pathologic events. The normal squamous mucosa is believed to be destroyed by chronic gastroesophageal reflux disease (GERD), which can cause ulceration of the esophagus followed by development of Barrett's esophagus (BE). BE is the only known potential precursor of these cancers of the gastroesophageal junction, and the incidence of BE is also increasing. Epidemiologic studies have shown that diets high in fruit and vegetable consumption are inversely associated with EA/GCA and BE. It is hypothesized that flavonoids, which are a group of bioactive polyphenolic compounds that are naturally occurring in fruits, vegetables, and beverages of plant origin, partially account for the risk reduction of fruits and vegetables on these tumors. Experimental studies have supported this hypothesis and have shown that flavonoids regulate cell cycle, proliferation, and apoptosis, which have important chemotherapeutic effects against these tumors. A number of flavonoids are also COX-2 inhibitors and some can suppress COX-2 transcription. Epidemiologic studies have shown a modest reduction in risk of EA/GCA and BE in users of non-steroidal anti-inflammatory drugs (NSAIDS), including aspirin, which are COX-2 inhibitors. However, NSAIDS can have severe side effects so their clinical usage is limited. Therefore, it is of interest to develop a preventin strategy for these tumors that is acceptable for general use. To investigate this potential association between flavonoids and EA/GCA and BE, an ancillary study will be performed to address two specific aims. The first specific aim will determine whether flavonoid consumption is associated with EA/GCA risk from data that was collected as part of a multicenter, population-based case-control study conducted in Connecticut, New Jersey, and western Washington State. The parent study included 293 EA subjects, 261 GCA subjects, and 695 frequency matched control subjects. The second specific aim will determine whether flavonoid consumption is associated with BE risk from data that was collected in a case-control study conducted in western Washington State. The parent study included 193 BE subjects and 211 individually matched control subjects. The two parent case-control studies assessed usual dietary intake using a similar validated food frequency questionnaire (FFQ). For the proposed study, two flavonoid-specific databases will be developed by linking each FFQ on frequency of dietary intake and portion size with existing USDA flavonoid databases. If we are able to demonstrate that total flavonoids or a class of flavonoids are associated with BE or EA/GCA, there is potential to use flavonoids as a risk reduction strategy. This would allow some EA and GCA to be prevented before individuals develop these lethal cancers. PUBLIC HEALTH RELEVANCE: Esophageal and gastric cardia adenocarcinoma have very poor survival prognoses (normally less than a year), and the only known potential precursor of these cancers is Barrett's esophagus. If we can show an association between flavonoids, which are a naturally occurring compound found in fruits and vegetables, and esophageal adenocarcinoma, gastric cardia adenocarcinoma, or Barrett's esophagus, there is potential to use flavonoids as a risk reduction strategy. This would allow some esophageal or gastric cardia adenocarcinoma to be prevented before individuals develop these deadly cancers.

描述（由申请方提供）：食管/贲门腺癌和巴雷特食管风险摘要。在过去的30-40年里，在美国和其他西方国家，食管腺癌（EA）和贲门腺癌（GCA）的发病率比任何其他癌症都增长得更快。EA和GCA似乎是从正常粘膜内层通过一系列病理事件发展而来的。正常鳞状粘膜被认为是由慢性胃食管反流病（GERD），这可能会导致食管溃疡，随后发展为巴雷特食管（BE）的破坏。BE是这些胃食管连接部癌症的唯一已知的潜在前体，并且BE的发病率也在增加。流行病学研究表明，水果和蔬菜消费量高的饮食与EA/GCA和BE呈负相关。据推测，黄酮类化合物是一组天然存在于水果，蔬菜和植物来源的饮料中的生物活性多酚化合物，部分原因是水果和蔬菜对这些肿瘤的风险降低。实验研究支持了这一假设，并表明黄酮类化合物调节细胞周期，增殖和凋亡，对这些肿瘤具有重要的化疗作用。许多类黄酮也是考克斯-2抑制剂，并且一些类黄酮可以抑制考克斯-2转录。流行病学研究表明，使用非甾体抗炎药（NSAIDS）（包括阿司匹林，一种考克斯-2抑制剂）可适度降低EA/GCA和BE的风险。然而，NSAIDS可能具有严重的副作用，因此其临床使用受到限制。因此，开发一种可被普遍接受的针对这些肿瘤的预防策略是有意义的。为了研究黄酮类化合物与EA/GCA和BE之间的这种潜在关联，将进行辅助研究以解决两个特定目标。第一个具体目标将确定类黄酮消费是否与EA/GCA风险相关，这些数据是作为在康涅狄格州，新泽西和西部华盛顿州进行的多中心，基于人群的病例对照研究的一部分收集的。母研究包括293名EA受试者，261名GCA受试者和695名频率匹配的对照受试者。第二个具体目标将确定类黄酮的消费是否与BE风险的数据，收集在西部华盛顿州进行的病例对照研究。母研究包括193例BE受试者和211例个体匹配的对照受试者。两项母病例对照研究使用类似的经验证的食物频率问卷（FFQ）评估了日常饮食摄入量。对于拟议的研究，将通过将每个关于饮食摄入频率和份量的FFQ与现有的USDA类黄酮数据库联系起来，开发两个类黄酮特异性数据库。如果我们能够证明总黄酮或一类黄酮类化合物与BE或EA/GCA相关，则有可能使用黄酮类化合物作为风险降低策略。这将使一些EA和GCA在个体发展这些致命癌症之前得到预防。 公共卫生相关性：食管和贲门腺癌的生存期非常短（通常不到一年），这些癌症唯一已知的潜在前体是巴雷特食管。如果我们能证明类黄酮（一种在水果和蔬菜中发现的天然化合物）与食管腺癌、贲门腺癌或巴雷特食管之间的关联，就有可能使用类黄酮作为降低风险的策略。这将使一些食管或贲门腺癌，以防止个人发展这些致命的癌症。