Case Control Study of Pancreas Cancer in Shanghai, China

中国上海胰腺癌病例对照研究

• 批准号: 7141788
• 负责人: Harvey A Risch
• 金额: $ 54.83万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-23 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7141788
• 关键词: Acidity; Acids; Affect; Age; Americas; Behavior; Blood specimen; Breast; Cancer Etiology; Case-Control Studies; Cessation of life; China; Chinese American; Chinese People; Chronic; Climate; Colorectal Cancer; Connecticut; Country; Cytokine Gene; Daily; Diagnosis; Diet; Dietary Factors; Dietary Nitrite; Disease; Etiology; Exposure to; Frequencies; Gastric Acid; Gastric ulcer; Gender; Genetic; Genetic Polymorphism; Genetic Variation; Green tea; Helicobacter; Helicobacter pylori; Incidence; Individual; Infection; Inflammatory; Institutes; Intake; Interview; Interviewer; Life Style; Lung; Malignant Neoplasms; Malignant neoplasm of pancreas; Multivariate Analysis; Nitrites; Nitrosamines; Nitroso Compounds; Numbers; Nutrient; Pancreas; Pathway interactions; Pattern; Persons; Pharmaceutical Preparations; Population; Population Control; Prevalence; Prevention; Process; Production; Prostate; Pylorus; Questionnaires; Recording of previous events; Registries; Relative Risks; Risk; Risk Factors; Stomach; Structure; Testing; Tobacco use; Training; Variant; aged; base; cancer risk; carcinogenesis; cigarette smoking; cytokine; dietary constituent; disorder risk; drinking; food standard; insight; interest; malignant stomach neoplasm; men; mortality; programs; protective effect

DESCRIPTION (provided by applicant): In the US in 2005, about 32,200 individuals will be diagnosed with pancreas cancer, and nearly that number will die from it, making it the 4th most frequent cause of cancer death, after lung, breast/prostate and colorectal cancer. Over the lifetime, more than 1% of the population is affected. Survival with this cancer is dismal: one year about 20-30%, and 5-year, about 5%. Compared to the US, pancreas cancer is less frequent in China (and gastric cancer more frequent), yet risk factors for these cancers?gastric colonization by Helicobacter pylori, cigarette smoking, nitrite or A/-nitrosamine intake?are more prevalent in China. We recently developed a new hypothesis on the etiology of pancreatic cancer, concerning A/-nitrosamine exposures and chronic excess gastric acidity, the latter typically resulting from Helicobacter colonization, modulated by host inflammatory cytokine polymorphisms. For individuals with H. pylori, these cytokine variants act as a genetic switch, increasing risk of pancreas cancer and decreasing risk of gastric cancer, or vice versa. Ethnic frequency differences in carriage of these cytokine variants likely explains the lower risk of pancreas cancer in China compared to the US. We propose to conduct, in urban Shanghai, China, a population-based case- control study of Helicobacter, genetic, and dietary factors. In total, 1,000 pancreas-cancer cases aged 35-79 years will be identified prospectively via the ultra-rapid case accession program of the Shanghai Cancer Institute. About 1,000 randomly selected population controls will be frequency matched to the cases by age and gender, and will be identified by use of the Shanghai Residents Registry. All subjects will be interviewed in person by trained interviewers using a standardized, structured questionnaire that will include tobacco use, a standard food-frequency questionnaire for the local Chinese diet, and other factors specific to our hypotheses. A small blood sample will be drawn to test for colonization by H. pylori, and for DMA polymorphisms in inflammatory cytokine genes relevant to our hypotheses. Average daily intake of nitrite, A/-nitroso compounds, and other dietary constituents and nutrients will be calculated from the diet histories, and uni- and multivariate analyses will be used to estimate relative risks for comparison of the cases with the controls. The Helicobacter, genetic and dietary factors will also be compared to the same variables in our ongoing similar population-based pancreas cancer study in Connecticut. Understanding the etiology of pancreas cancer will help to provide direction for modifying individual behaviors related to risk. In addition to reduction of cigarette smoking, Helicobacter and dietary factors are modifiable and could be involved in a program to reduce risk of pancreas cancer.

描述（由申请人提供）：在2005年，在美国，将诊断出约32,200人患有胰腺癌，几乎这一数字将死亡，这使其成为肺，乳腺/前列腺癌和结肠癌后的第四最常见的癌症死亡原因。在一生中，超过1％的人口受到影响。患有这种癌症的生存令人沮丧：一年约20-30％，5年，约5％。与美国相比，胰腺癌在中国（和胃癌更频繁）的频率较小，但是这些癌症的危险因素是幽门螺杆菌，吸烟，亚硝酸盐或A/硝酸胺摄入的胃定植？在中国更为普遍。我们最近开发了关于胰腺癌病因的新假设，该假设是关于A/ - 亚硝基胺暴露和慢性过量胃酸性的，后者通常是由宿主炎性细胞因子多态性调节的host炎性杆菌定殖导致的。对于患有幽门螺杆菌的个体，这些细胞因子变体充当遗传转换，增加了胰腺癌的风险和降低胃癌的风险，反之亦然。这些细胞因子变体的运输频率差异可能会解释中国胰腺癌的较低风险与美国相比。我们建议在中国城市上海进行一项基于人群的病例控制研究，对螺旋杆菌，遗传和饮食因素的研究。总共将通过上海癌症研究所的Ultra-Rapid Case Accession计划来确定1,000名胰腺癌病例，年龄在35-79岁之间。大约有1,000个随机选择的人口控制将符合年龄和性别案件的频率，并通过使用上海居民注册表来确定。所有受试者都将通过训练有素的访调员亲自采访，使用标准化的结构化问卷，其中包括烟草使用，一份标准的中国饮食中的标准食品频率问卷以及其他特定于我们的假设的因素。将吸引一个小的血液样本，以测试幽门螺杆菌的定殖，以及与我们假设相关的炎性细胞因子基因中的DMA多态性。亚硝酸盐，A/ - 硝酸化合物以及其他饮食成分和营养素的平均每日摄入量将根据饮食史进行计算，并且将使用单个和多变量分析来估计相对的风险，以比较病例与对照组的相对风险。在康涅狄格州正在进行的类似基于人群的胰腺癌研究中，还将将螺旋杆菌，遗传和饮食因素与相同的变量进行比较。了解胰腺癌的病因将有助于为修改与风险相关的个人行为提供指导。除了减少吸烟外，还可以修改甲细菌和饮食因素，并可能参与降低胰腺癌风险的计划。