ETHNIC DIFFERENCES IN GENOTYPE AND DISEASE RISK

基因型和疾病风险的种族差异

• 批准号: 6413629
• 负责人: William W Au
• 金额: $ 27.93万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6413629
• 关键词: blood chemistry; cardiovascular disorder; cervix neoplasms; chemical related neoplasm /cancer; clinical research; disease /disorder proneness /risk; gene expression; genetic susceptibility; genotype; human genetic material tag; human subject; lung neoplasms; outcomes research; racial /ethnic difference; smoking; tobacco abuse

Cigarette smoking is recognized to be responsible for a substantial portion of the serious disease burden such as lung cancer, cardiovascular disease and cervical carcinoma in the population. It is also well documented that some individuals are particularly susceptible to cigarette smoke-induced health outcomes. The hypothesis of this study is that inheritance of ""unfavorable"" version of certain polymorphic metabolizing genes contributes to the susceptibility. The rationale is that individuals with these ""unfavorable"" genes have increased body burden of reactive metabolites from chemicals in cigarete smoke to cause increased cellular damage leading to increased risk for development of disease. Patients with the mentioned diseases (lung cancer, cardiovascular disease and cervical carcinomas) will be recruited to investigate the influence of the ""unfavorable"" metabolizing genes on these cigarette smoke associated health outcome. Controls with matching to the three groups of patients will be selected from one cohort of individuals. In many cases, the same individuals will serve as controls for the three patient groups, thus providing a cost effective way for the study. GCRC will be asked to provide assistance in collecting blood samples from the controls. Lung cancer patients will be described in detail here as a representative for the other two patient groups. Blood samples will be collected from 800 lung cancer patients and 800 matched controls for the genetic analysis. The targeted polymorphic metabolizing genes are CYP1A1, CYP2D6, CYP2E1, GSTM1, GSTT1, NAT1, and NAT2. It is expected that the patients will be significantly over-represented by individuals who have inherited combinations of these ""unfavorable"" genes. The patients with the ""unfavorable"" genes are expected to have worse clinical history than those with ""favorable"" genes. The differential distribution of the ""unfavorable"" genes among different ethnic groups is expected to explain the ethnic differences in disease outcome.

吸烟被认为是造成人口中很大一部分严重疾病负担的原因，例如肺癌、心血管疾病和宫颈癌。也有充分证据表明，有些人特别容易受到吸烟引起的健康后果的影响。本研究的假设是遗传某些多态代谢基因的“不利”版本有助于易感性。其基本原理是，拥有这些“不利”基因的个体，会增加来自香烟烟雾中化学物质的反应性代谢物的身体负担，从而导致细胞损伤增加，从而增加患病风险。将招募上述疾病（肺癌、心血管疾病和宫颈癌）的患者，研究“不利”代谢基因对这些香烟烟雾相关健康结果的影响。将从一组个体中选择与三组患者相匹配的对照。在许多情况下，相同的个体将作为三个患者组的对照，从而为研究提供了一种经济有效的方法。将要求GCRC提供协助，收集对照者的血液样本。这里将详细描述肺癌患者作为其他两组患者的代表。将收集800名肺癌患者和800名匹配对照者的血液样本进行基因分析。靶向多态性代谢基因为CYP1A1、CYP2D6、CYP2E1、GSTM1、GSTT1、NAT1和NAT2。预计这些患者中，遗传了这些“不利”基因组合的个体所占比例将明显过高。携带“不利”基因的患者比携带“有利”基因的患者有更差的临床病史。“不利”基因在不同族群之间的差异分布有望解释疾病结局的种族差异。