Genetic and modifying factors that determine the risk of brain tumors.
Some modifying factors may determine the risk of brain tumors. Until now, it could not be attempted to identify people at risk and also to improve significantly disease progression. Current therapy consists of surgical resection, followed by radiation therapy and chemotherapy. Despite of these treatments, the prognosis for patients is poor. In this review, we highlight general aspects concerning genetic alterations in brain tumors, namely astrocytomas, glioblastomas, oligodendrogliomas, medulloblastomas and ependymomas. The influence of these genetic alterations in patients' prognosis is discussed. Mutagen sensitivity is associated with cancer risk. The convincing studies that linked DNA damages and DNA repair alterations with brain tumors are also described. Another important modifying factor is immunity. General immune response against cancer, tumor microenvironment and immune response, mechanisms of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immuno-suppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well established that there is association between brain tumor risk and mutagen sensitivity, which is highly heritable. Primary brain tumors cause depression in systemic host immunity; local immuno-suppressive factors and immunological characteristics of tumor cells may explain the poor prognosis and DNA damages responses can alert immune system. However, it is necessary to clarify if individuals with both constitutional defects in immune functions and genetic instability have higher risk of developing brain tumors. Cytogenetic prospective studies and gene copy number variations analysis also must be performed in peripheral lymphocytes from brain tumor patients.
Botucatu Medical School, São Paulo State University, Rua General Telles 267, Botucatu, SP, Brazil. acmontelli@uol.com.br
Terezinha de Cresci Braga
Tde C
Montelli
Maria Terezinha Serrão
MT
Peraçoli
Silvia Regina
SR
Rogatto
Ramon
R
Kaneno
Cíntia Helena Braga Montelli
CH
do Prado
Patrícia de Medeiros Cardassi
Pde M
Rocha
D001812:Blood-Brain Barrier / Q000502:physiology; D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D003713:Dendritic Cells / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D007107:Immune System / Q000502:physiology; D007167:Immunotherapy / Q000379:methods; D014411:Neoplastic Stem Cells; D012307:Risk Factors; D019139:Tumor Escape; D059016:Tumor Microenvironment