CORE--MOLECULAR EPIDEMIOLOGY AND ECOGENETICS

描述：本研究核心的总体目标是开发和 验证癌症易感性的遗传标记。通过将 将分子遗传学和细胞遗传学纳入种群研究，研究人员 希望能深入了解基因和基因之间复杂的相互作用 癌症的环境决定因素。特别令人感兴趣的是低收入人群 可能调节人对环境暴露的反应的外显性基因 并对散发性癌症的病因学作出贡献。具体目标包括 保持和扩大核心之间的沟通和科学互动 和其他中心成员，以及非中心成员；加强当前 并促进未来在遗传易感性领域的研究活动 应对环境疾病；刺激和促进核心内和核心间赠款 续签和新的调查人员发起的赠款提案；并在 跨研究和设施核心的咨询和协作角色 包括概念开发、研究设计、人体组织采购和 环境数据收集。这一核心的主要研究领域 包括：1)评估DNA损伤和修复的表型标记 作为致癌易感性的标志，2)评估 部分代谢和DNA修复基因及DNA加合物基因的多态性 肺癌、膀胱癌、乳腺癌和胰腺癌的病因，以及3) 联合应用开发癌症风险评估统计模型 生物标记物以及基因-表型和代孕-组织标记物的相关性。 正在进行或完成核心4内部协作研究和核心间协作研究 研究内容包括：1)肺癌检查的病例对照研究 烟草致癌的细胞遗传学和分子决定因素，2)一项研究 遗传和环境决定因素，包括植物雌激素摄入量， 前列腺癌进展，3)中国人脑胶质瘤的遗传流行病学研究 家族史和遗传易感标记的关系，4)一项研究 微卫星不稳定性与双侧乳腺癌风险，5)一项研究 遗传多态、流行病学危险因素和乳房差异 不同种族之间的癌症生存率，6)DNA加合物，P53的研究 突变谱、氧化DNA损伤和乳腺癌风险 绝经前妇女，7)遗传性遗传的分子遗传学研究 非息肉病性结直肠癌，8)一项影响 与年龄相关的结直肠癌风险，9)两项研究评估 晚期前列腺癌的环境和遗传决定因素， 10)毛细胞白血病治疗后的第二种恶性肿瘤的研究， 急性髓细胞白血病，11)皮肤恶性黑色素瘤和 非黑色素瘤皮肤癌，连锁和连锁不平衡的研究， 性状方法，13)膀胱癌遗传易感性的研究， 14)Barrett‘s食道诱变剂敏感性及进展的研究 15)对肥胖的遗传、激素和行为决定因素的研究， 16)一项埃及人乳腺癌和结直肠癌的初步研究 有机氯农药暴露，以及一项初步研究，以检查 肺组织诱变剂敏感性、氧化损伤与DNA加合物的关系 癌症。 此核心所述的长期目标是开发经过验证的风险模型 对于癌症，如肺癌，同时考虑到 众多遗传和环境因素的影响以及疾病的性质 小组(妇女、不吸烟者、青年受试者、少数民族等)。 未来的计划包括将烟草和解的资金用于 德克萨斯州将建立档案实验室用于长期存储 以及对生物样本的跟踪和一个集中的基因分型核心。它 还计划在营养流行病学领域扩大，并在其 分子流行病学研究，包括脑部和淋巴系恶性肿瘤。 未来的计划还包括开发一种基因分型芯片， 与Genometrix合作，扩展CRID网站和 对大型数据库进行多元统计分析的实现 将通过将芯片技术纳入研究而产生。

Description: The overall goal of this research core is to develop and validate genetic markers for cancer susceptibility. By incorporating molecular genetics and cytogenetics into population studies, the investigators hope to gain insights into the complex interactions between genetic and environmental determinants of cancer. Of particular interest are the low penetrance genes that may modulate one's response to environmental exposures and contribute to the etiology of sporadic cancers. Specific aims include maintaining and expanding communication and scientific interaction among Core and other Center members, as well as non-Center members; strengthen current and promote future research activities in the area of genetic susceptibility to environmental disease; stimulate and facilitate intra- and inter-Core grant renewals and new investigators-initiated grant proposals; and serve in consultative and collaborative roles across research and facility cores to include concept development, study design, human tissue procurement and environmental data collection. Major areas of research focus in this Core encompass: 1) the assessment of phenotypic markers of DNA damage and repair as markers of susceptibility to carcinogenesis, 2) the evaluation of polymorphisms in select metabolic and DNA repair genes and DNA adducts in the etiology of lung, bladder, breast, and pancreatic cancers, and 3) the development of statistical models for cancer risk assessment by combining biomarkers and for genotype-phenotype and surrogate-tissue marker correlation. Intra-Core 4 and inter-Core collaborative studies being conducted or completed include the following: 1) a case-control study of lung cancer examining cytogenetic and molecular determinants of tobacco carcinogenesis, 2) a study of genetic and environmental determinants, including phytoestrogen intake, of prostate cancer progression, 3) a genetic epidemiologic study of gliomas in relation to family history and genetic susceptibility markers, 4) a study of microsatellite instability and the risk of bilateral breast cancer, 5) a study of genetic polymorphisms, epidemiologic risk factors and differences in breast cancer survival among different ethnic groups, 6) a study of DNA adducts, P53 mutation spectrum, oxidative DNA damage and breast cancer risk among premenopausal women, 7) a study of molecular genetics of hereditary nonpolyposis colorectal cancer, 8) a study of modifier genes that influence age-associated risk of colorectal cancer, 9) two studies evaluating environmental and genetic determinants of advanced prostate cancer, 10) studies of second malignancies after treatment for hairy cell leukemia, acute myelocytic leukemia, 11) a study of cutaneous malignant melanoma and non-melanoma skin cancer, 12) a study of linkage and linkage disequilibrium, methods for traits, 13) a study of genetic susceptibility of bladder cancer, 14) a study of mutagen sensitivity and progression in Barrett's esophagus, 15) a study of the genetic, hormonal and behavioral determinants of obesity, 16) a pilot study of breast and colorectal cancers among Egyptians and organochlorine pesticides exposures, and 17) a pilot study to examine associations of mutagen sensitivity, oxidative damage and DNA adducts in lung cancer. The stated long term goal of this Core is to develop a validated risk model for cancer, such as lung cancer, to take into account simultaneously the effects of numerous genetic and environmental factors and the nature of subgroups (women, never-smokers, young subjects, ethnic minorities, etc). Future plans include the use of funds from the Tobacco Settlement for the State of Texas to establish an archival laboratory for the long-term storage and tracking of biological specimens and a centralized genotyping core. It also plans to expand in the area of nutritional epidemiology, and in its molecular epidemiologic studies to include brain and lymphoid malignancies. Future plans also include the development of a genotyping chip, in collaboration with Genometrix, expansion of the CRED website and implementation of multivariate statistical analysis to the large database that will be generated by incorporating chip technologies into studies.