ETHNIC DIFFERENCES IN GENOTYPE AND DISEASE RISK

吸烟被认为是造成人口中肺癌、心血管疾病和宫颈癌等严重疾病负担的主要原因。 也有充分的证据表明，一些人特别容易受到香烟烟雾引起的健康后果的影响。 本研究假设某些代谢基因的“不利”版本的遗传多态性与易感性有关。 其基本原理是，具有这些“不利”基因的个体增加了吸烟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，导致疾病发展的风险增加。 将招募患有所述疾病（肺癌、心血管疾病和宫颈癌）的患者以研究“不利”代谢基因对这些香烟烟雾相关的健康结果的影响。 将从一组个体中选择与三组患者匹配的对照。 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具有成本效益的方法。 将要求GCRC协助采集对照组的血样。 肺癌患者将在这里作为其他两个患者组的代表进行详细描述。 将从800名肺癌患者和800名匹配的对照组中采集血液样本进行遗传分析。 靶向多态性代谢基因为CYP1A1、CYP2D6、CYP2E1、GSTM 1、GSTT1、NAT1和NAT2。 预计这些患者将由遗传了这些“不利”基因组合的个体显著过度代表。 预期携带“不利”基因的患者的临床病史比携带“有利”基因的患者更差。 “不利”基因在不同种族群体中的差异分布有望解释疾病结果的种族差异。

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.