Case Control Study of Pancreas Cancer in Shanghai, China

描述（由申请人提供）：2005年，在美国，大约有32,200人将被诊断出患有胰腺癌，几乎这个数字将死于胰腺癌，使其成为继肺癌，乳腺癌/前列腺癌和结肠直肠癌之后的第四大癌症死亡原因。在一生中，超过1%的人口受到影响。这种癌症的生存率很低：1年约为20-30%，5年约为5%。与美国相比，胰腺癌在中国发病率较低（胃癌发病率较高），但这些癌症的危险因素是什么呢？幽门螺杆菌的胃定植、吸烟、亚硝酸盐或A/-亚硝胺的摄入？在中国更为普遍。我们最近提出了一个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量，后者通常由幽门螺杆菌定植引起，受宿主炎症细胞因子多态性的调节。对于幽门螺杆菌患者来说，这些细胞因子的变异起到了基因开关的作用，增加了患胰腺癌的风险，降低了患胃癌的风险，反之亦然。携带这些细胞因子变异的种族频率差异可能解释了中国胰腺癌风险低于美国的原因。我们建议在中国上海城市进行一项以人群为基础的幽门螺杆菌、遗传和饮食因素的病例对照研究。总共1000例35-79岁的胰腺癌病例将通过上海癌症研究所的超快速病例加入计划进行前瞻性鉴定。大约1000个随机选择的人口对照将根据年龄和性别与病例进行频率匹配，并将通过上海居民登记处进行识别。所有受试者将由训练有素的采访者亲自访谈，使用一份标准化、结构化的问卷，其中包括烟草使用情况、中国当地饮食的标准食物频率问卷，以及其他符合我们假设的因素。将抽取少量血液样本，以检测幽门螺杆菌的定植，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。将根据饮食史计算亚硝酸盐、A/-亚硝基化合物和其他膳食成分和营养素的平均每日摄入量，并使用单因素和多因素分析来估计与对照组比较的相对风险。幽门螺杆菌、遗传和饮食因素也将与我们正在康涅狄格州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指导。除了减少吸烟，幽门螺杆菌和饮食因素是可以改变的，可能与降低胰腺癌风险的计划有关。

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.