PLCO Trial Etiologic and Early Marker Study

前列腺癌、肺癌、结直肠癌和卵巢癌（PLCO）筛查试验是一项大型随机试验，旨在确定筛查这些癌症是否能降低死亡率。该试验由NCI与美国10个临床中心的研究人员签订合同进行。该研究包括大约155,000名志愿者（从1993年到2001年招募，年龄在55-74岁之间，平均分配到试验的筛查组和对照组）。PLCO病因学和早期标志物研究（EEMS）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试验背景下收集的数据和样本，包括：2.所有参与者的基线人口统计和危险因素信息。所有参与者的食物频率问卷（FFQ）3 .在筛选参与者的6轮筛选中，每轮对血液标本进行分离。对照受试者的颊细胞样本；关于所有癌症发病率和选定的其他医疗状况的信息。PLCO EEMS的研究显示饮食相关因素与腺瘤风险相关，包括膳食纤维、肉类烹饪方法、血清硒、低钙摄入量和钙敏感受体的基因变异。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代谢的基因改变了风险。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择性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相关，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[4,5-b]吡啶（PhIP）的高温熟食导致风险增加，而只有最高水平的胰岛素样生长因子-1 （IGF-1）与前列腺癌有关。PLCO试验中候选基因的遗传学研究揭示了SHBG中snp与前列腺癌风险的相关性。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通路基因变异相关的前列腺和乳腺癌风险。BPC3和癌症易感性遗传标记（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，考虑结肠癌的病因，也与其他研究小组合作。淋巴瘤和白血病的研究正在进行中，膀胱癌和子宫内膜癌的研究正在计划中；随着患有各种癌症的研究对象数量的增加，努力将会扩大。

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. Studies of lymphoma and leukemia are in progress, and studies of bladder and endometrial cancer are being planned; efforts will expand as numbers of study subjects with a variety of cancers increase.