TY - JOUR VL - 78 SP - 3731 N1 - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions. IS - 13 SN - 1538-7445 UR - http://doi.org/10.1158/0008-5472.CAN-17-3175 JF - Cancer Research A1 - Rossi, G A1 - Redaelli, V A1 - Contiero, P A1 - Fabiano, S A1 - Tagliabue, G A1 - Perego, P A1 - Benussi, L A1 - Bruni, AC A1 - Filippini, G A1 - Farinotti, M A1 - Giaccone, G A1 - Buiatiotis, S A1 - Manzoni, C A1 - Ferrari, R A1 - Tagliavini, F TI - Tau Mutations Serve as a Novel Risk Factor for Cancer EP - 3739 AV - public Y1 - 2018/07// ID - discovery10056116 N2 - In addition to its well-recognized role in neurodegeneration, tau participates in maintenance of genome stability and chromosome integrity. In particular, peripheral cells from patients affected by frontotemporal lobar degeneration carrying a mutation in tau gene (genetic tauopathies), as well as cells from animal models, show chromosome numerical and structural aberrations, chromatin anomalies, and a propensity toward abnormal recombination. As genome instability is tightly linked to cancer development, we hypothesized that mutated tau may be a susceptibility factor for cancer. Here we conducted a retrospective cohort study comparing cancer incidence in families affected by genetic tauopathies to control families. In addition, we carried out a bioinformatics analysis to highlight pathways associated with the tau protein interactome. We report that the risk of developing cancer is significantly higher in families affected by genetic tauopathies, and a high proportion of tau protein interactors are involved in cellular processes particularly relevant to cancer. These findings disclose a novel role of tau as a risk factor for cancer, providing new insights in the various pathologic roles of mutated tau. PB - AMER ASSOC CANCER RESEARCH KW - neurodegeneration; cancer; tau; MAPT; mutation; risk factor; epidemiology; bioinformatics ER -