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									                                                                                   Thematic Field: Environmental Factors and Health




     Hereditary Factors
     Modify Risk of Bone Tumour Following
     Radiation Exposure
     Institute of Pathology




                                                                     1


     D
             ue to the additive interaction
             of several susceptibility loci a
             hereditary predisposition for                         0.8
                                                Tumour incidence




     radiation-induced bone tumours                                                              5xS
                                                                   0.6
     (osteosarcomas) may develop in
     mice. In man, this type of tumour is                                                                       BALB
                                                                   0.4
     becoming increasingly important as
     a secondary tumour following child-
                                                                   0.2
     hood radiation therapy. Our search                                                                             CBA
                                                                                                                             5xR
     for inherited susceptibility factors in
                                                                     0
     mice shows, that the accidental co-                                 0   200               400                  600                  800
     segregation of high-risk alleles from
                                                   Cumulative osteosarcoma incidence                      Latency period/days
     both parental animals results in a            following injection with the bone-
     significant increase in the individual         seeking alpha-emitter thorium227
     bone tumour risk in some of their             shows that a combination of suscepti-
     progeny.                                      bility loci from the parental BALB/c and
                                                   CBA/CA strains (dotted lines) may occur
         A hereditary influence on the              in the F2 generation (solid lines), which
                                                   results in a hypersensitive (5 x S) or
     risk of bone tumour development                                                                 to the case of familial cancer
                                                   hyperresistant (5 x R) phenotype in the
     following radiation exposure has              offspring.                                        syndromes mentioned, are not
     only been known for a few rare                                                                  characterized by the existence of
     hereditary diseases which lead to a                                                             close relatives with early or frequent
     high frequency of a number of                                                                   tumor incidences. Therefore, the
     tumours in some families. Due to                                                                examination of a family history
     their severe effects, which often             the mutations underlying these so-                may not be very promising. More
     affect very young patients, however,          called familial cancer syndromes are              characteristic indications of a
                                                   rarely found in the population.                   hereditary predisposition, however,
                                                                                                     would be: Unusually young age of
                                                       In genetic tests of radiation-                tumour development or patients
                                                   induced bone tumours in various                   with multiple tumours.
                                                   mouse strains we could identify                       This work brought us a good
                                                   chromosome sections which had                     deal closer to the aim of determi-
                                                   been unknown, and which only                      ning such a hereditary predispositi-
                                                   increase the frequency of this type               on by a molecular test, before any
                                                   of cancer, when they are combined.                clinical symptoms are manifested.
                                                   In these instances an accidental
                                                   combination of risk alleles from
                                                   both parents may result in a heredit-             Literature:
                                                   ary predisposition for these bone                   Rosemann, M., Kuosaite, V., Kremer, M.,
                                                   tumours, which had not been seen                    Favor, J., Quintanilla-Martinez, L., Atkinson,
                                                   in previous generations.                            M.J.: Multilocus inheritance determines
       Dr. Michael Rosemann                                                                            predisposition to alpha-radiation induced
                                                                                                       bone tumour-igenesis in mice.
       Institute of Pathology                          Translating our findings to the                  Int. J. Cancer 118, 2132-2138, 2006.

       Telephone +49 - 89 / 31 87-26 28            situation in the human population
       rosemann@gsf.de                             one might expect to find hyper-
                                                   sensitive person which, in contrast

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