DNA Repair Gene Polymorphysms and Pancreatic Cancer

描述(申请人提供)：胰腺癌是美国男性或女性癌症相关死亡的第四大原因。在所有癌症中，它的5年存活率最低(4%)，由于其快速致命的病程和缺乏中间终点或早期标记物，一直难以研究。吸烟是为数不多的有记录的环境风险因素之一。这项研究将使用以前收集的生殖系DNA和流行病学数据，来自最大的基于人群的胰腺癌病例对照研究之一，以调查胰腺癌风险与候选DNA修复、细胞周期控制和氧化防御基因的多态之间的关系。这项主要研究是1994年至2001年在旧金山湾区进行的，使用随机数字拨号和医疗保健财务管理局的名单来确定控制措施。基因组DNA和问卷信息可用于309个病例和964个基于人群的对照。众所周知，DNA修复途径与纠正烟草烟雾等制剂引起的各种形式的损伤有关。最近的研究表明，DNA修复途径与参与细胞周期调节的途径相互作用，从而使细胞周期延迟或停止，从而实现最佳的DNA修复。DNA修复能力因个体而异，很可能是遗传的。致癌物代谢和DNA修复的遗传变异已被证明在吸烟相关癌症的易感性中发挥了作用。我们将分析病例和对照的基因组DNA，寻找参与碱基切除修复、核苷酸切除修复、双链断裂修复、直接修复、细胞周期控制和氧化防御途径的已知基因多态性。我们将估计基因和等位基因的频率，检查主要基因(基因)的影响，并探索潜在的基因吸烟和基因-基因相互作用，因为它们与胰腺腺癌的风险有关。我们预计这些数据将有助于我们对疾病机制的理解，并最终可能改善胰腺癌的预防、检测和治疗。

DESCRIPTION (provided by applicant): Pancreatic cancer is the fourth leading cause of cancer-related deaths among men or women in the U.S. It has the lowest 5-year survival (4%) of all cancers and has been difficult to study due to its rapidly fatal course and the lack of intermediate endpoints or early markers for the disease. Cigarette smoking is one of the few documented environmental risk factors. This study will use previously collected germ-line DNA and epidemiologic data from one of the largest population-based, case-control studies of pancreatic cancer to investigate associations between risk of adenocarcinoma of the pancreas and polymorphisms in candidate DNA repair, cell-cycle control, and oxidant defense genes. The main study was conducted in the San Francisco Bay Area between 1994 and 2001 and used random digit dialing and Health Care Finance Administration lists to identify controls. Genomic DNA and questionnaire information is available on 309 cases and 964 population-based controls. DNA repair pathways are known to be involved in correcting diverse forms of damage induced by agents such as tobacco smoke. Recent studies indicate that DNA repair pathways cross talk with pathways involved in cell cycle regulation such that cell-cycle delay or arrest allows for optimal DNA repair. DNA repair capacity is known to vary among individuals and is likely to be genetic. Genetic variation in carcinogen metabolism and DNA repair has been shown to play a role in susceptibilities to smoking-related cancers. We will analyze genomic DNA from cases and controls for known polymorphisms in genes involved in pathways for base excision repair, nucleotide excision repair, double-strand break repair, direct repair, cell-cycle control, and oxidant defense. We will estimate genotype and allele frequencies, examine main gene (genotype) effects, and explore potential genotypesmoking and genotype-genotype interactions as they relate to the risk of adenocarcinoma of the pancreas. We anticipate that these data will contribute to our understanding of disease mechanisms, and may ultimately improve the prevention, detection and treatment of pancreatic cancer.