Genetic susceptibility to malignant mesothelioma and exposure to asbestos: The influence of the familial factor

Background: Asbestos is the principal etiological factor of malignant mesothelioma (MM), accounting for more than 80% of all tumor cases. However, other co-factors, including genetic susceptibility may play a role in the etiology of this disease, possibly modulating the effects of exposure to asbestos and other carcinogenic mineral fibers. The frequent report of familial clustering was the first indication supporting the involvement of genetic factors. Therefore, we performed an extensive literature search to evaluate existing studies reporting familial cases of MM. Methods: Published reports addressing the issue of familial susceptibility to MM have been searched through PubMed using keywords and free text tools. Eighty-two citations were retrieved and 20 of them actually reported a familial cluster of MM. Three more articles were identified through the references. The probability that the observed familial clusters of mesothelioma could have randomly occurred in exposed families was evaluated with the Family History Score Z_i (FHS_i). Results: The result of this analysis suggested that clustering of MM cases in families exposed to asbestos may be explained with the additional contribution of other familial factors. The FHS_i allowed to reject the hypothesis of random occurrence of these clusters with a probability of a first type error ranging between 1 per cent and 1 per billion. Conclusions: The evaluation of the published materials supports the hypothesis that - although familial clustering of MM is largely attributable to shared asbestos exposure - the additional contribution of factors dealing with genetic susceptibility may play a role in the etiology of MM.