Z01 CP005804-08203 (Z01) | |||
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Title | Environmental And Genetic Lung cancer Etiology (EAGLE) | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Caporaso, Neil | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $738,883 | Project Dates | 06/01/2001 - N/A |
Fiscal Year | 2008 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Behavioral and Social Science (20.0%) Biochemical Epidemiology (45.0%) Cancer (100.0%) Smoking Behavior (40.0%) |
Lung (100.0%) | ||
Research Type | |||
Interactions of Genes and/or Genetic Polymorphisms with Exogenous and/or Endogenous Factors Interventions to Prevent Cancer: Personal Behaviors That Affect Cancer Risk |
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Abstract | |||
The Environment And Genetics in Lung cancer Etiology (EAGLE) study is a large population-based case-control study that includes behavior, treatment and survival information in addition to the traditional epidemiological and biomarker data to elucidate exposure, gene, and disease links. EAGLE consists of 2101 incident, primary lung cancer cases, and 2120 population-based controls enrolled in Italy. In EAGLE, we conducted several investigations in: (1) environmental and (2) genetic risk factors, as well as (3) genomic analyses in tumors. (1) Epidemiological analyses showed etiologic differences by histology for smoking, occupation, nonmalignant lung diseases and meat intake. (2) Family history of lung cancer, family history of smoking, and SNPs in metabolic genes also showed different risks by histology. To identify novel susceptibility regions, we designed a genome-wide association study (GWAS), including EAGLE and ~1700 subjects from the PLCO cohort, which was awarded funding by the NHGRI Genes, Environment and Health Initiative (GEI). Over 500,000 SNPs have been genotyped to identify genetic susceptibility to lung cancer risk and survival, and to smoking persistence. The GWAS now includes also other cohort studies from DCEG and meta-analysis of summary GWAS data from several studies worldwide. Further steps will include fine mapping of verified regions of interest, gene resequencing, and functional assays to provide biological clues for the findings. Analyses of smoking and other phenotypes across GEI-funded GWAS are planned. (3) We found a strong gene expression smoking signature in adenocarcinoma and noninvolved lung tissue that was associated with lung cancer risk and survival. Methylation and microRNA analyses in tissue from the same subjects are ongoing. Future plans include analyses of tumor genetic alterations and their integration with GWAS data. |