PLCO Trial Etiologic and Early Marker Study

PLCO 试验病因学和早期标志物研究

• 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
• 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

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.

前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验(PLCO)是一项大型随机试验，旨在确定筛查这些癌症是否会降低死亡率。这项试验是由NCI与美国十个临床中心的研究人员签订的合同进行的。这项研究包括大约155,000名志愿者(从1993年至2001年招募，年龄55-74岁，平均分配到试验的筛查和控制部门)。PLCO病因学和早期标志物研究(EEM)支持癌症和其他疾病的病因学和早期检测研究。EEMS使用在PLCO试验中收集的数据和样本，包括：1.所有参与者的基线人口和风险因素信息，2.所有参与者的食物频率问卷(FFQ)，3.筛查参与者在每一轮筛查中的分级血液样本，4.对照参与者的口腔细胞样本，以及5.所有癌症发病率和选定的其他医疗条件的信息。PLCO EEM的研究表明，与腺瘤风险相关的饮食因素包括膳食纤维、肉类烹调方法、血清硒、低钙摄入量和钙感应受体的基因变异。烟草使用与腺瘤风险密切相关，有证据表明参与烟草烟雾中多环芳烃和芳香胺成分新陈代谢的基因改变了风险。其他与结直肠腺瘤风险相关的因素包括胰岛素样生长因子和特定的DNA修复相关基因多态性。前列腺癌风险与蔬菜摄入量有关，特别是十字花科蔬菜，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相关，与其他报告一致；血清硒也仅与吸烟者的风险相关。含有2-amino-1-methyl-6-phenylimidazo[4，5-b]pyridine的高温熟肉会导致风险增加，而只有最高水平的胰岛素样生长因子-1与前列腺癌有关。对PLCO试验候选基因的遗传学研究表明，SHBG中的SNPs与前列腺癌风险有关。通过乳腺癌和前列腺癌队列联盟(BPC3)，他们正在评估与类固醇激素和胰岛素样生长因子途径中的基因变异相关的前列腺癌和乳腺癌风险。对BPC3和癌症遗传易感性标记(CGEMS)项目的研究正在确定与8q24区域基因变异相关的前列腺癌风险。结肠腺瘤的研究现在正在扩大，以考虑结肠癌的病因，也与其他研究小组合作。全基因组联合研究已被用于淋巴瘤、肾脏、胰腺、膀胱癌、前列腺癌、乳腺癌和肺癌。