Case-Control Study of Pancreas Cancer Etiologic Factors

描述（由申请人提供）：2001年，在美国，约有29，000例胰腺癌新发病例，几乎有29，000人死于胰腺癌，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，黑人的比例略高于白人。这种癌症的生存率很低：一年约20- 30%，五年约5%。大多数患者表现为晚期疾病，标准治疗不会改变渐进的致命过程。除了可能占5%的病例的主要基因原因外，胰腺癌的一个已知风险因素是吸烟，吸烟会使风险增加一倍。对饮食因素的研究并不完全一致，但确实表明动物产品摄入的风险较高，而水果或蔬菜的消费风险较低。本申请描述了胰腺癌病因学的一个新假说，并提供了大量的实验室和流行病学证据来支持这一假说。为了检验这一假说，我们将在CT状态下进行一项基于人群的病例对照研究，以检查感染、遗传、饮食、生活方式和病史因素。总共有600例年龄在35-79岁之间的胰腺癌病例将通过耶鲁大学快速病例确定共享资源的超快速计划进行前瞻性识别。大约600名随机选择的人群对照将按年龄和性别与病例进行频率匹配。 将使用增强的随机数字拨号方法识别对照品。所有受试者都将由经过培训的访谈人员使用标准化结构化问卷进行访谈，其中包括烟草使用和病史部分、标准食物频率/补充剂问卷以及关于我们假设的其他特定因素的问题。将抽取少量血液样本用于检测某些感染的暴露情况，以及与我们的假设相关的四种DNA多态性。将根据饮食史计算饮食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组比较的相对风险。这里要检查的因素很少受到关注，胰腺癌，拟议的研究将系统地评估他们在一个充满活力的，大规模的和综合的项目。

DESCRIPTION (provided by applicant): In the US in 2001, there were about 29,000 new cases of cancer of the pancreas, and nearly that number died 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, with blacks having a bit higher rates than whites. Survival with this cancer is dismal: one year about 20-30%, and 5-year, about 5%. Most patients present with advanced disease, and the standard treatments do not much alter the progressive, fatal course. Aside from major-gene causes underlying perhaps 5% of cases, the one known risk factor for pancreatic cancer is cigarette smoking, which doubles the risk. Studies of dietary factors have not been entirely consistent but do suggest associations of higher risk with animal product intake and lower risk with consumption of fruits or vegetables. This application describes a new hypothesis on the etiology of pancreatic cancer, and provides a substantial body of laboratory and epidemiologic evidence in support of it. To examine this hypothesis, we will conduct, in the state of CT, a population-based case-control study to examine infectious, genetic, dietary, lifestyle and medical history factors. In total, 600 pancreas-cancer cases aged 35-79 years will be identified prospectively via the ultra-rapid program of the Rapid Case Ascertainment Shared Resource at Yale. About 600 randomly selected population controls will be frequency matched to the cases by age and gender. Controls will be identified using enhanced random-digit dialing methods. All subjects will be interviewed in person by trained interviewers using a standardized, structured questionnaire that will include sections on tobacco use and medical history, a standard food frequency/supplements questionnaire, and questions about other factors specific to our hypothesis. A small blood sample will be drawn for use in testing for exposure to certain infections, and for four DNA polymorphisms relevant to our hypothesis. Average daily intake of dietary 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 factors to be examined here have received little attention with respect to pancreas cancer, and the proposed study will evaluate them systematically in a vigorous, large-scale and integrated project.