Genetic Epidemiology of Lung Cancer and Smoking

Overview

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.

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.