Case Control Study of Pancreas Cancer in Shanghai, China

描述(申请人提供)：在2005年的美国，大约有32,200人将被诊断出患有胰腺癌，几乎有这个数字的人将死于胰腺癌，使其成为癌症死亡的第四大原因，仅次于肺癌、乳腺癌/前列腺癌和结直肠癌。在一生中，超过1%的人口受到影响。这种癌症的存活率令人沮丧：一年约为20%-30%，五年约为5%。与美国相比，中国的胰腺癌较少(而胃癌较多)，但这些癌症的危险因素--幽门螺杆菌定植、吸烟、亚硝酸盐或亚硝胺摄入--在中国更普遍。我们最近对胰腺癌的病因学提出了一个新的假说，涉及A/-亚硝胺暴露和慢性胃酸过多，后者通常是由幽门螺杆菌定植引起的，受宿主炎症细胞因子基因多态性的调节。对于幽门螺杆菌携带者来说，这些细胞因子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。这些细胞因子变异体携带的种族频率差异可能是中国患胰腺癌风险低于美国的原因。我们建议在上海市区开展一项以人群为基础的病例对照研究，研究螺杆菌、遗传和饮食因素。总共有1,000例年龄在35-79岁之间的胰腺癌病例将通过上海癌症研究所的超快速病例登记计划进行前瞻性识别。随机选择的大约1000名人口控制人员将按年龄和性别与病例频率匹配，并将通过上海居民登记系统进行识别。所有受试者都将接受训练有素的面试者的面谈，使用标准化、结构化的调查问卷，其中包括吸烟情况、中国当地饮食的标准食物频率调查问卷，以及针对我们假设的其他因素。将抽取少量血液样本，以测试幽门螺杆菌的定植，以及与我们的假设相关的炎性细胞因子基因的DMA多态。亚硝酸盐、A/-亚硝基化合物以及其他饮食成分和营养素的平均每日摄入量将从饮食历史中计算出来，并将使用单变量和多变量分析来估计相对风险，以便将病例与对照组进行比较。在康涅狄格州进行的类似的基于人群的胰腺癌研究中，螺杆菌、遗传和饮食因素也将与相同的变量进行比较。了解胰腺癌的病因将有助于为改变个体与风险相关的行为提供方向。除了减少吸烟，幽门螺杆菌和饮食因素是可改变的，并可能参与一项降低胰腺癌风险的计划。

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.