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: 8434846
• 负责人: MARILIE D. GAMMON
• 金额: $ 6.77万
• 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 2014-05-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8434846
• 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.

描述（由申请人提供）：类黄酮、食管/贲门腺癌和巴雷特食管风险摘要。过去 30-40 年来，在美国和其他西方国家，食管腺癌 (EA) 和贲门腺癌 (GCA) 的发病率增长速度比任何其他癌症都要快。 EA 和 GCA 似乎是通过一系列病理事件从正常粘膜内层发展而来。据信，正常的鳞状粘膜会被慢性胃食管反流病（GERD）破坏，从而导致食管溃疡，继而发展为巴雷特食管（BE）。 BE 是胃食管连接部癌症唯一已知的潜在前兆，并且 BE 的发病率也在增加。流行病学研究表明，富含水果和蔬菜的饮食与 EA/GCA 和 BE 呈负相关。据推测，类黄酮是一组天然存在于水果、蔬菜和植物源饮料中的生物活性多酚化合物，部分原因是水果和蔬菜降低了这些肿瘤的风险。实验研究支持了这一假设，并表明类黄酮调节细胞周期、增殖和凋亡，对这些肿瘤具有重要的化疗作用。许多黄酮类化合物也是 COX-2 抑制剂，有些可以抑制 COX-2 转录。流行病学研究表明，使用非甾体类抗炎药 (NSAIDS)（包括阿司匹林（COX-2 抑制剂））的患者，EA/GCA 和 BE 的风险略有降低。然而，非甾体抗炎药可能有严重的副作用，因此其临床使用受到限制。因此，开发一种可以普遍使用的针对这些肿瘤的预防策略是有意义的。为了调查类黄酮与 EA/GCA 和 BE 之间的潜在关联，将进行一项辅助研究来解决两个具体目标。第一个具体目标是根据在康涅狄格州、新泽西州和华盛顿州西部进行的多中心、基于人群的病例对照研究收集的数据，确定类黄酮的摄入是否与 EA/GCA 风险相关。母研究包括 293 名 EA 受试者、261 名 GCA 受试者和 695 名频率匹配对照受试者。第二个具体目标是根据在华盛顿州西部进行的病例对照研究收集的数据来确定黄酮类化合物的摄入是否与 BE 风险相关。母研究包括 193 名 BE 受试者和 211 名单独匹配的对照受试者。两项家长病例对照研究使用类似的经过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，将通过将每个有关膳食摄入频率和份量的 FFQ 与现有的美国农业部黄酮类数据库联系起来，开发两个类黄酮特定数据库。如果我们能够证明总黄酮类化合物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降低风险的策略。这将使一些 EA 和 GCA 在个体患上这些致命癌症之前得到预防。