Lung cancer is the commonest cause of cancer death in developed countries and throughout the world. Worldwide, the estimated number of new lung cancer cases in 2002 is 1.2 million (12.3% of all new cancer cases). Over 90% of these new cases will die as a result of the disease [1
]. The death rate for lung cancer exceeds the combined total for breast, prostate and colon cancer in developed countries [1
]. Cigarette smoking is the main risk factor for lung cancer, accounting for about 90% of cases in men and 70–85% of cases in women [2
]. Genetic risk factors contribute to an individual's susceptibility to lung cancer, which is illustrated by the fact that about 16% of long-term smokers will develop lung cancer [3
]. Unfortunately, no effective clinical tests are available for early detection of lung cancer. Smoking cessation programs are critical, but ex-smokers continue to have a higher risk to develop lung cancer. Even more than 40 years after cessation compared with never-smokers [4
]. These days ex-smokers comprise almost 50% of all new lung cancer cases in developed countries, indicating a strong need for a search for new means of early diagnosis in lung cancer and chemoprevention in this high-risk group (4). Nevertheless, an important issue for these approaches is the appropriate selection of an optimal high-risk population.
Long-term carcinogenic exposure (cigarettes smoke) is characterized by genetic alteration and diffuse injury of the airways surface [5
]. These changes in epithelium can give rise to cancer at multiple points, for that reason named field cancerization. Genetic changes detected in premalignant lesions or malignant in one region of the field, translate into an increased risk of cancer development throughout the entire field. Therefore, it can be concluded that cigarettes smoking may induce field cancerization whereas cancer in non-smokers is clonally derived, i.e. by single cell transformed is the ancestor of all cells that compose the neoplasm [6
The consequence of this is that the non-cancerous tissue in non-smoker patient with primary lung cancer should not show any alteration compared to normal, whereas in smokers due to field cancerization morphological and genetic alteration may possibly be observed. Probably, this genetic alteration in smokers could serve for early detection of lung cancer.
Identification of individuals at greatest risk of developing lung cancer could enhance the efficacy of intervention modalities, thereby greatly reducing mortality from this disease. One strategy for identifying these people is to establish molecular markers that reflect the severity of their cancerization field.
Microarray can simultaneously measure the expression of thousands of mRNAs. They are used in many biological fields and in different species. This high-throughput technique can be used to predict the function of unknown genes, in medical diagnostics, in biomarker discovery, to infer networks from the regulatory interactions between genes, and to investigate the mechanisms by which a drug, disease, mutation and environmental condition affects gene expression and cell function. Large datasets are produced, particularly from whole-genome arrays, and public databases hold substantial quantities of gene-expression information [9
Adenocarcinoma (AC) is becoming the most common form of lung cancer. It has increased relative to other histological types of lung cancer over the last several decades [11
These observations lead us to investigate the gene expression in non-involved lungs from patients with adenocarcinoma and compare it to gene expression in non-involved lung tissue from non-smokers. We used the U133A GeneChip array (Affymetrix, Santa Clara, CA), GeneSpring analysis software and the Ingenuity Pathway Analysis software.