Cadmium, K-ras, and Pancreatic Cancer in Egypt

描述（由申请人提供）： 胰腺癌是一种致命的疾病，迅速剥夺患者的生活质量和数量。它是美国癌症死亡的第五大原因。2001年，估计有29 200例新病例被诊断出来，28 900人死于这种疾病。胰腺癌的中位生存期为6个月，只有4%的患者在诊断后存活5年。鉴于其发病率和几乎全部死亡率，显然有必要大幅增加研究工作，以了解，预防和控制这种疾病。 虽然胰腺癌在发展中国家（包括埃及大部分地区）很少见，但埃及东北尼罗河三角洲地区为研究胰腺癌提供了一个独特的环境，因为：1）胰腺癌病例数量众多; 2）该地区居民血清镉水平高;和3）来自该地区的患者的胰腺癌肿瘤的独特分子病理学特征[异常高的GGT -> GTT比率（甘氨酸-->缬氨酸）K-ras突变]。 镉被怀疑是胰腺癌的致癌物质，大量的病例和早发性疾病以及该人群中肿瘤的独特K-ras突变可能是由高镉暴露引起的。我们提出了一个试点研究，以产生一个假设，即胰腺癌，在这一人群中，是由高水平的暴露于环境镉。我们将招募150名胰腺癌对照和150名年龄、性别和居住地匹配的医院对照。我们将研究终身流行病学，环境和癌症家族史，以确定新的环境或生活方式相关的因素，预测胰腺癌的风险，在这个人群中，高不良环境暴露。我们还将检测病例和对照的血清镉水平以及病例肿瘤中的K-ras突变类型，以确定独特的突变类型是否与较高的血清镉水平或其他环境暴露相关。这项研究可能定义镉在胰腺癌病因学中的作用，并可能为未来在胰腺癌流行病学中基因-环境相互作用的研究奠定基础。

DESCRIPTION (provided by applicant): Pancreatic cancer is a lethal disease that quickly deprives patients of both quality and quantity of life. It is the fifth leading cause of cancer death in the United States. In 2001, an estimated 29,200 new cases were diagnosed, and 28,900 people died from the disease. The median survival of pancreatic cancer is six months and only 4% of patients are alive five years after diagnosis. Given its incidence and almost entire fatality, substantially increased research efforts are clearly warranted to understand, prevent, and control this disease. Although pancreatic cancer is rare in developing countries, including most of Egypt, the northeast Nile Delta region of Egypt offers a unique setting for studying pancreatic cancer because of: 1) its large number of pancreatic cancer cases; 2) the high serum cadmium levels in residents of the region; and 3) the unique molecular pathologic features of pancreatic cancer tumors of patients from this region [unusually high rate of GGT --> GTT (glycine --> valine) K-ras mutation]. Cadmium has been suspected as a carcinogen for pancreatic cancer and the large number of cases and early-onset disease in addition to the unique K-ras mutations of tumors in this population may be caused by high cadmium exposures. We propose a pilot study to generate a hypothesis that pancreatic cancer, in this population, is caused by high levels of exposure to environmental cadmium. We will recruit 150 pancreatic cancer controls and 150 age-, sex- and residence-matched hospital controls. We will examine lifetime epidemiologic, environmental and cancer family histories to identify novel environmental or lifestyle-related factors that predict risk for pancreatic cancer in this population with high adverse environmental exposures. We will also test serum cadmium levels in cases and controls and K-ras mutation types in tumors of cases to define if the unique mutation types are associated with higher serum cadmium levels or other environmental exposures. This study may define the role of cadmium in the etiology of pancreatic cancer and may set the stage for future studies on gene-environmental interactions in the epidemiology of pancreatic cancer.