microRNA pattern in tumoral lung tissues from former- and non-smokers: a possible footprint for environmental and genetic risk factors evaluation.

For the last decade the interest of microRNA as a possible early biomarker for lung-cancer has increased. Less attention has been focused in using microRNA as a biomarker to study the contribution of environmental exposure to air pollutants in non-smokers lung cancer patients. The aim of this thesis is the identification of environmental related microRNA pattern in collected tissues from a total of 64 formal- and non- smoker patients recruited in a three-year observational study. The identified patterns may be used as early predictors of lung cancer, as well as environmental-related footprints. Through microRNA-chip array analysis of lung tissue, it was studied the expression of 2549 microRNAs. A differential analysis between healthy and tumoral tissue showed the presence of 273 microRNA differentially regulated, 222 were down-regulated and 51 up-regulated. Differential analysis was also applied to identify environmental pollution related microRNAs and finding microRNA deregulation in Passive Smoking at home (n=8), Passive smoking at work (n=1), Vehicle traffic at home (n=53), home distance from Etna Volcano (n=21), and home Type radon risk (n=19) exposures. A second biomarker, Benzo(a)Pyrene-DNA adducts levels in blood, was also studied to understand its correlation to the above-mentioned environmental factors. The specificity of this biomarker was minor than microRNA pattern biomarker, but it was strongly correlated to vehicle traffic pollution. The analysis of the microRNA environmental signatures indicates the contribution of environmental factors to the analysed lung cancers in the following decreasing rank: (a) vehicle traffic, (b) passive smoke, (c) radon, and (d) volcano ashes. These results provide evidence that microRNA analysis can be used to investigate the contribution of environmental factors in human lung cancer occurring in non-smokers