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: 8079555
• 负责人: Harvey A Risch
• 金额: $ 55.64万
• 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 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8079555
• 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; 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; Malignant neoplasm of prostate; Multivariate Analysis; Nitrites; Nitrosamines; Nitroso Compounds; Nutrient; Pancreas; Pathway interactions; Pattern; Persons; Pharmaceutical Preparations; Population; Population Control; Prevalence; Prevention; Process; Production; Pylorus; Questionnaires; Recording of previous events; Registries; Relative Risks; Risk; Risk Factors; Stomach; Structure; Testing; Tobacco use; Training; Variant; aged; cancer risk; carcinogenesis; cigarette smoking; cytokine; dietary constituent; disorder risk; drinking; food standard; insight; interest; malignant stomach neoplasm; men; mortality; population based; 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）：2005 年，在美国，大约有 32,200 人被诊断出患有胰腺癌，并且几乎这个数字将死于胰腺癌，使其成为继肺癌、乳腺癌/前列腺癌和癌症之后的第四大最常见的癌症死亡原因。结直肠癌。在一生中，超过 1% 的人口受到影响。这种癌症的生存率很低：一年的生存率约为 20-30%，五年的生存率约为 5%。与美国相比，胰腺癌在中国的发病率较低（胃癌的发病率较高），但这些癌症的危险因素——幽门螺杆菌在胃定植、吸烟、亚硝酸盐或A/-亚硝胺的摄入——在中国却更为普遍。我们最近提出了关于胰腺癌病因学的新假设，涉及 A/-亚硝胺暴露和慢性胃酸过多，后者通常是由螺杆菌定植引起的，并受宿主炎症细胞因子多态性的调节。对于幽门螺杆菌感染者来说，这些细胞因子变体充当基因开关，增加患胰腺癌的风险并降低患胃癌的风险，反之亦然。这些细胞因子变体携带的种族频率差异可能解释了中国患胰腺癌的风险低于美国的原因。我们建议在中国上海城区开展一项基于人群的螺杆菌、遗传和饮食因素病例对照研究。上海癌症研究所的超快速病例登记计划将总共前瞻性识别1000例35-79岁的胰腺癌病例。大约 1,000 名随机抽取的人口对照将按年龄和性别与病例进行频率匹配，并通过上海居民登记处进行识别。所有受试者都将由经过培训的采访员使用标准化的结构化调查问卷进行亲自采访，其中包括烟草使用情况、针对中国当地饮食的标准食物频率调查问卷以及我们假设的其他具体因素。将抽取少量血液样本来测试幽门螺杆菌的定植情况，以及与我们的假设相关的炎症细胞因子基因中的 DMA 多态性。将根据饮食历史计算亚硝酸盐、A/-亚硝基化合物以及其他膳食成分和营养素的平均每日摄入量，并将使用单变量和多变量分析来估计病例与对照之间比较的相对风险。螺杆菌、遗传和饮食因素也将与我们在康涅狄格州正在进行的类似的基于人群的胰腺癌研究中的相同变量进行比较。了解胰腺癌的病因将有助于为改变与风险相关的个人行为提供方向。除了减少吸烟之外，螺杆菌和饮食因素也是可以改变的，并且可以参与降低胰腺癌风险的计划。