DNA Repair Gene Polymorphysms and Pancreatic Cancer

DNA修复基因多态性与胰腺癌

基本信息

批准号：
6944249
负责人：
ERIC J DUELL
金额：
$ 25.96万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-01 至 2008-07-09
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：胰腺癌是美国男性或女性与癌症相关死亡的第四个主要原因，在所有癌症中，其5年生存率最低（4％），由于其迅速致命的病程和缺乏中间端口或早期标记或疾病的早期标记，因此很难研究。吸烟是少数记录的环境风险因素之一。这项研究将使用先前收集的种系DNA和流行病学数据，来自胰腺癌的最大的，基于人群的病例对照研究，以研究胰腺腺癌的风险与候选DNA修复，细胞周期控制和氧化防御基因的胰腺腺癌风险与多态性的风险之间的关联。这项主要研究是在1994年至2001年间在旧金山湾区进行的，并使用随机数字拨号和医疗保健财务管理列表来识别控制措施。基因组DNA和问卷信息可在309例和964例基于人群的对照方面获得。已知DNA修复途径参与纠正烟草烟雾等药物引起的各种形式的损害。最近的研究表明，DNA修复途径与涉及细胞周期调节的途径进行交流，从而使细胞周期延迟或停滞可实现最佳的DNA修复。已知DNA修复能力在个体之间有所不同，并且可能是遗传的。致癌代谢和DNA修复的遗传变异已被证明在与吸烟有关的癌症的敏感性中起作用。我们将分析来自病例和对照的基因组DNA，以控制碱性切除修复途径，核苷酸切除修复，双链破裂修复，直接修复，细胞周期控制和氧化剂防御的基因中已知的多态性。我们将估计基因型和等位基因频率，检查主要基因（基因型）效应，并探索潜在的基因型吸血和基因型基因型相互作用，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，并最终可以改善胰腺癌的预防，检测和治疗。