Genetic Epidemiology of Lung Cancer and Smoking
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Study type: Observational

Summary: 
      We will conduct an interdisciplinary case-control/sib-pair study of lung cancer designed to
      explore the genetic determinants both of lung cancer and of smoking. The study includes
      biospecimen collection as well as exposure information with power to address main genetic
      effects and gene-environment interactions.

      This is an integrated proposal designed to address two major issues: the genetic determinants
      of lung cancer in smokers and the genetic determinants of smoking. Other important issues
      will be addressed in the study with a marginal additional cost to the main design. The study
      achieves excellent power for studying the main effects of genetic factors that are relatively
      common and good power for formal tests of interactive effects.

      Using a case-control design, with questionnaire, medical record abstraction, and blood
      collection, we will investigate: main effects of genes on lung cancer risk; gene-environment
      and gene-gene effects in lung cancer etiology; gene effects on smoking persistence; gene
      effects on ever-never smoking; gene-psychological interactions in smoking behaviors.

      In addition, we will collect viable lymphocytes from all study subjects and tumor,
      metaplastic and normal tissue samples from 100 surgical cases. With these data and tissues,
      we will be able to study: genetic instabilities in lung cancer tissue in relation to specific
      exposures, genotype, persistence of smoking, and clinical presentation of lung cancer;
      histologic characteristics of lung cancer in relation to genotype, gene expression, somatic
      mutations, and smoking; functional assays in viable lmphocytes in relation to genotype, gene
      expression.

      Finally, we will identify lung cancer-affected siblings of cases, and the unaffected siblings
      in the same sibships. This sample will permit us to: replicate associations found in the
      case-control sample with an alternative analytical method based on transmission statistics;
      address some population stratification issues.
    

Detailed description: 
      This is an interdisciplinary multicenter case-control study of lung cancer situated in Milan
      Italy, designed to explore the genetic determinants both of lung cancer and of smoking. We
      enrolled newly diagnosed lung cancer cases within a defined area around Milan Italy, and
      population-based controls from the same area. The study includes biospecimen collection as
      well as epidemiological and clinical data.

      This is an integrated proposal designed to address two major issues: the genetic determinants
      of lung cancer and the genetic determinants of smoking. Other important issues arc addressed
      in the study with a marginal additional cost to the main design. The study achieves excellent
      power for studying the main effects of genetic factors that are relatively common and good
      power for formal tests of interactive eftects.

      Using a case-control design, with questionnaire, medical record abstraction, and blood
      collection. we can investigate:

        -  main effects of genes on lung cancer risk

        -  gene-environment and gene-gene effects in lung cancer etiology

        -  gene effects on smoking persistence

        -  genes effects on ever-never smoking

      In addition, we have collected viable lymphocytes from all study subjects and tumor,
      metaplastic and normal tissue samples from at least 400 surgical cases. With these data and
      tissues, we can study:

        -  genetic instabilities in lung cancer tissue in relation to specific exposures, genotype,
           persistence of smoking, and clinical presentation of lung cancer;

        -  histologic characteristics of lung cancer in relation to genotype, gene expression,
           methylation. somatic mutations, and smoking;

        -  functional assays in viable lymphocytes in relation to genotype, gene expression

      Moreover. we are collecting clinical reports of treatments, quality of life, recurrence,
      toxicities, and survival from all cases that consented. With this material we will be able to
      link the genetic profiles of the cases with data on therapy efficacy, toxicity and survival,
      to contribute to the improvement of treatment for lung cancer.
    

Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Lung cancer cases consecutively enrolled from 13 hospitals and population-based controls
        with no cancer.
      
Keywords: Population-Based Case Control Study; Lung Cancer; Epidemiology; Smoking; Smokers; Genetics