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.
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