419 Nbn Gene Mutation I171V as a Potential Risk Factor for Children Malignancies

NBN (former NBS1 ) gene is considered as one of the low to moderate cancer susceptibility gene. At least four germinal NBN mutations have been found in several malignancies in adults. In our studies we observed the high incidence of germinal mutation I171V of NBN gene in breast, colorectal, larynx cancer and in multiple primary tumors. In present study we would like to answer the question whether I171V germinal mutation of NBN gene may constitue risk factor for solid tumors and acute leukemias in children. The frequency of this mutation has been analysed in patients with neuroblastoma (n=66), Wilms' tumor (n=54), medulloblastoma (n=57), rhabdomyosarcoma (n=82) and acute lymphoblastic leukemia (n=173) hospitalized in Pediatric Oncology, Hematology and Bone Marrow Transplantation Department Poznan University of Medical Sciences in the years 1987 and 2010. 2947 anonymous blood samples collected on Guthrie cards drawn from the newborn screening program of the Wielkopolska voivodship have been used as controls. The study was approved by the Ethic Committee of the University of Medical Sciences in Poznań. All the patients and population controls came from the same geographical region. I171V mutation of the NBN gene has been observed in 7 children with acute lymphoblastic leukemia and in 5 control cases. Among children with solid tumors only in one child with medulloblastoma I171V variant has been found. In conclusion I171V germinal mutation in contrary to adults can't be considered as a risk factor for children malignancies except acute lymphoblastic leukemia. Supported in part by Grant NN 407 016235 .