Exposure to asbestos fibers is a major risk factor for malignant pleuralmesothelioma (MPM), lung cancer,
and other non-neoplastic conditions, such as asbestosis and pleural plaques. However, in the last decade
many studies have shown that polymorphism in the genes involved in xenobiotic and oxidative
metabolism or in DNA repair processes may play an important role in the etiology and pathogenesis of
these diseases. To evaluate the association between diseases linked to asbestos and genetic variability we
performed a review of studies on this topic included in the PubMed database. One hundred fifty-nine
citations were retrieved; 24 of them met the inclusion criteria and were evaluated in the review. The most
commonly studied GSTM1 polymorphism showed for all asbestos-linked diseases an increased risk in
association with the null genotype, possibly linked to its role in the conjugation of reactive oxygen
species. Studies focused on GSTT1 null and SOD2 Ala16Val polymorphisms gave conflicting results, while
promising results came from studies on a1-antitrypsin in asbestosis and MPO in lung cancer. Among
genetic polymorphisms associated to the risk of MPM, the GSTM1 null genotype and two variant alleles of
XRCC1 and XRCC3 showed increased risks in a subset of studies. Results for the NAT2 acetylator status,
SOD2 polymorphism and EPHX activity were conflicting. Major limitations in the study design, including
the small size of study groups, affected the reliability of these studies. Technical improvements such as
the use of high-throughput techniques will help to identify molecular pathways regulated by candidate
genes