Molecular biology and genetic engineering advanced laboratory methods used in combination with analytical epidemiology and bioinformatic tools help to understand the mechanisms of chemical carcinogenesis and to identify at the molecular level, specific exogenous or/and host factors that play a role in human cancer causation. Molecular epidemiology of lung cancer has focused on environmental causes because is believed that one of the main factor of incidence is exogenous and hence preventable. Biomarkers of internal dose, of biologically effective dose, of response and susceptibility give important information for prevention and treatment of the disease. Molecular endpoints used in studies of molecular carcinogenesis which give key information about both genetic and environmental susceptibility factors: include metabolites in body fluids, DNA and protein adducts, mutations in reporter genes, in oncogenes and in suppressor genes, genomic instability, aberrant gene expression and altered cell culture.

Polymorphisms in genes coding for enzymes involved in the metabolism and detoxification of carcinogens including many cytochromes P-450 that codify for Phase I enzymes or genes that codify for conjugation Phase II enzymes, or for DNA repair enzymes and for tumour suppressor proteins might be determinant in the risk to lung cancer by environmental exposure. The frequency of many of these polymorphisms is related to lung cancer susceptibility and might varies within different etnias suggesting that some populations around the world might be more susceptible to environmental carcinogens pollutants.

It is hoped that a more unified approach to cancer epidemiology and genetics will identify those combinations of genetic susceptibility and environmental exposures that lead to significant increases in risk at the individual and population level. This could lead to changes in lifestyle and avoidance of specific exposures in genetically susceptible individuals.

The complete sequencing of the human genome is allowing the identification of expressed sequences and polymorphic sequences providing information that is increasingly available to medical researchers that make possible to visualize in the near future more personalized protocols for the disease treatment as well as to identify persons with higher risk. Thus, the discovery of genes involved in the pathogenesis may lead to new targets for diagnosis and treatment. A knowledge in the polymorphisms that make each of us unique individuals could be the key in the future for predicting individual risks for developing the disease as well as the individual responses to antineoplasic drugs. The cancer researchers are presently searching in genome databases trying to identify candidates for genes important in lung cancer pathogenesis. Chromosomal aberrations and loci of chromosomal deletions have already been defined in lung cancer and with the increasing availability of gene maps we are now seeing an acceleration in our recognition of new genes involved in lung cancer pathogenesis.

Some of the most promising applications of genomics to lung cancer research come from measurements of the gene expression of cancer cells. Thus, serial analysis of gene expression, oligonucleotide arrays and cDNA arrays are now tools that allow investigators to measure the expression of thousands of gene in a single experiment. This help to learn about selected clones, genes over expressed in certain types of lung cancers and to identify potential therapeutic targets. Gene arrays have offered the opportunity to test large numbers of gene as potential predictive markers of clinical applications.

New genomic techniques will facilitate changes in tumour classification and consequently will be more useful for therapy. Although gene expression patterns are closed linked to cell’s function, it is ultimately genetic alterations that are responsible for the cancer phenotype. Thus, for detecting mutations, genomic DNAs techniques such as oligonucleotide arrays can represent a series of different sequences for each gene, including wild type and single-base mistmatched sequences.

Promising new proteomics techniques might not only measure protein levels related to the disease but might also recognize post translational modifications of proteins. Integrating these measurements with those of gene expression could add a whole new dimension to our understanding of lung cancer. Due to poor survival rates, the development of novel techniques for early diagnosis, prevention and therapies is a high priority to diminish lung cancer incidence, and mortality. Thus, clinical scientists, pathologists, molecular biologists, statisticians and informatic specialists working as a team will make lung cancer genomics and proteomic programs successful. Collaborative efforts will be increasingly important in cancer research because sophisticated tools requires specialized expertise.