Case-Control Study of Pancreas Cancer Etiologic Factors

描述（由申请人提供）：2001年，美国约有29,000例胰腺癌新病例，几乎有这个数字死于胰腺癌，使其成为仅次于肺癌，乳腺癌/前列腺癌和结肠直肠癌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：1年约为20-30%，5年约为5%。大多数病人的病情已经发展到晚期，而标准的治疗方法并不能很大程度地改变病情的发展和致命的过程。除了可能导致5%病例的主要基因原因外，已知的胰腺癌风险因素之一是吸烟，它使风险增加一倍。对饮食因素的研究并不完全一致，但确实表明，摄入动物产品的风险较高，而摄入水果或蔬菜的风险较低。本应用程序描述了胰腺癌病因学的一个新假设，并提供了大量的实验室和流行病学证据来支持它。为了检验这一假设，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项目进行前瞻性鉴定。大约600个随机选择的人口对照将根据年龄和性别进行频率匹配。控制将使用增强的随机数字拨号方法进行识别。所有受试者将由训练有素的采访者亲自访问，使用标准化的结构化问卷，其中包括烟草使用和病史部分，标准食物频率/补充剂问卷，以及关于我们假设特定因素的问题。将抽取少量血液样本用于检测暴露于某些感染，以及与我们的假设相关的四种DNA多态性。根据饮食史计算膳食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病例与对照组比较的相对风险。这里要检查的因素在胰腺癌方面很少受到关注，建议的研究将在一个有力的、大规模的和综合的项目中系统地评估它们。

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.