PLCO Trial Etiologic and Early Marker Study

PLCO 试验病因学和早期标志物研究

基本信息

批准号：
8349572
负责人：
Ann Hsing
金额：
$ 229.4万
依托单位：
DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8349572
关键词：
2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]pyridine 8q24 Address Age Aromatic Amines Biochemical Biological Assay Bladder Blood specimen Breast Bronchi Calcium-Sensing Receptors Cancer Etiology Candidate Disease Gene Categories Cells Clinical Collaborations Collection Colon Carcinoma Colonic Adenoma Colorectal Colorectal Adenoma Colorectal Cancer Contracts Cooking Practices Cytogenetics DNA Repair Data Databases Demographic Factors Development Dietary Fiber Disease Disease Marker Division of Cancer Prevention Early Diagnosis Equipment and supply inventories Etiology Food Frequencies Genes Genetic Genetic Markers Genetic Polymorphism Genetic Variation High temperature of physical object Incidence Institutes Insulin-Like Growth Factor I Intake Investigation Kidney Lung Lymphoma Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of ovary Malignant neoplasm of prostate Meat Medical Metabolism Modification Molecular Epidemiology Nutritional Pancreas Participant Pathologic Pathway interactions Pleura Predisposition Prostate Questionnaires Recruitment Activity Reporting Research Research Activity Research Personnel Resources Risk Risk Factors SHBG gene Sampling Scientist Screening for Ovarian Cancer Screening for cancer Screening procedure Selenium Serum Smoker Somatomedins Tissue Microarray Tobacco smoke Tobacco use Trachea United States Validation Vegetables Vitamin E adenoma alpha Tocopherol arm calcium intake cancer epidemiology cancer genetics cancer risk cohort cooking cruciferous vegetable follow-up genetic analysis genome wide association study lycopene malignant breast neoplasm meetings member mortality randomized trial research study steroid hormone volunteer

项目摘要

The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial is a large randomized trial to determine if screening for these cancers reduces mortality. The Trial is carried out by the NCI under contract with investigators at ten clinical centers in the United States. The study includes approximately 155,000 volunteers (recruited from 1993 through 2001, ages 55-74, equally distributed to the screening and control arms of the Trial). The PLCO Etiology and Early Markers Study (EEMS) supports etiologic and early detection studies of cancers and other conditions. EEMS uses data and samples collected in the context of the PLCO Trial including: 1. Baseline demographic and risk factor information on all participants, 2. Food Frequency Questionnaires(FFQ) on all participants 3. Fractionated blood specimens at each of six screening rounds from screened participants, 4. Buccal cell samples from control participants, and 5. Information on all-cancer incidence and selected other medical conditions. Investigations in PLCO EEMS have shown dietary-related factors associated with adenoma risk, including dietary fiber, meat cooking practices, serum selenium, low calcium intake, and a gene variant in the calcium-sensing receptor. Tobacco use was strongly related to adenoma risk, with evidence of risk modification by genes involved in the metabolism of PAH and aromatic amine constituents of tobacco smoke. Other factors associated with risk of colorectal adenoma included insulin-like growth factors and selected DNA repair-related polymorphisms. Prostate cancer risk was related to vegetable intake, particularly cruciferous vegetables, while dietary and serum lycopene were unrelated to risk. Supplemental vitamin E and serum alpha-tocopherol were related to risk only in smokers, consistent with other reports; serum selenium was also related to risk in smokers only. High-temperature cooked meat containing 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) led to increased risk, while only the highest levels of insulin-like growth factor-1 (IGF-1) were related to prostate cancer. Genetic studies of candidate genes in the PLCO Trial have revealed associations with SNPs in SHBG and risk of prostate cancer. Through the Breast and Prostate Cancer Cohort Consortium (BPC3) are evaluating prostate and breast cancer risks related to gene variants in steroid hormone and insulin-like growth factor pathways. Investigations in BPC3 and the Cancer Genetic Markers of Susceptibility (CGEMS) project are identifying prostate cancer risks associated with gene variants in the 8q24 region. Colon adenoma studies are now being expanded to consider the etiology of colon cancer, also in collaboration with other research groups. Genome wide association studies (GWAS) have been condicted for canccers of the lymphoma, kidney, pancreas, bladder, prostate, breast, and lung.

前列腺，肺，结直肠癌和卵巢癌（PLCO）筛查试验是一项大型随机试验，以确定这些癌症的筛查是否会降低死亡率。该试验由NCI与美国十个临床中心的调查人员合同进行。该研究包括大约155,000名志愿者（从1993年到2001年，年龄在55-74岁之间招募，同样分布在试验的筛查和控制臂上）。 PLCO病因和早期标记研究（EEMS）支持癌症和其他疾病的病因学和早期检测研究。 EEM使用在PLCO试验的背景下收集的数据和样品，包括：1。所有参与者的基线人口统计和风险因素信息，2。对所有参与者的食物频率问卷（FFQ）3。从筛查参与者的六个筛选群中分离的血液标本，4。来自对照参与者的Buccal Cell样本，来自对照参与者的5。对所有患者和5个病情的信息。对PLCO EEM的研究表明，与腺瘤风险有关的饮食相关因素，包括饮食纤维，肉类烹饪实践，血清硒，低钙摄入量和钙敏感受体中的基因变体。烟草使用与腺瘤风险密切相关，其中涉及烟草烟雾的PAH和芳香胺成分的代谢的基因的风险改变证据。与结直肠腺瘤风险相关的其他因素包括胰岛素样生长因子和选定的DNA修复相关多态性。前列腺癌风险与蔬菜摄入量有关，尤其是十字花科蔬菜，而饮食和血清番茄红素与风险无关。补充维生素E和血清α-生育酚仅与吸烟者的风险有关，与其他报告一致；血清硒也仅与吸烟者的风险有关。含有2-氨基-1-甲基-6-苯基咪唑唑[4,5-B]吡啶（PHIP）的高温煮熟的肉（PHIP）导致风险增加，而最高水平的胰岛素样生长因子1（IGF-1）与前列腺癌有关。在PLCO试验中，候选基因的遗传研究揭示了SHBG中SNP的关联和前列腺癌的风险。通过乳腺癌和前列腺癌队列联盟（BPC3），正在评估与类固醇激素和胰岛素样生长因子途径相关的前列腺和乳腺癌风险。在BPC3和易感性癌症遗传标记（CGEM）项目中的研究正在鉴定与8q24区域中与基因变异有关的前列腺癌风险。现在正在扩大结肠腺瘤研究，以考虑与其他研究小组合作考虑结肠癌的病因。为淋巴瘤，肾脏，胰腺，膀胱，前列腺，乳房和肺部的癌症的癌症征测了基因组广泛的研究（GWAS）。