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Glutathione S-transferase M1 and T1 polymorphism in patients with renal cell
                                                        carcinoma

                                                       Natalija Krstić
                                Regional center for talented youth Belgrade II, natalija.krstic@yahoo.com

          1.  Introduction                                        4.  Research results


             The  results  of  many  researches  indicate  the  role  of    The frequency of  GSTM1 null genotype  was higher in
             Glutathione S-transferases (GST) as biomarkers of risk   patients with RCC (52%) compared to controls (51%).
             for  various  cancers,  including  renal  cell  carcinoma   GSTM1  null  individuals  exhibited  2,4-fold  increased
             (RCC).  (1)  Glutathione  S-transferases  (GST)  are  a  big   risk of RCC. The frequency of GSTT1 active genotype
             family of enzymes and in human body they take part in   was  higher  in  patients  with  RCC  (79%)  compared  to
             a phase of detoxication. (2) The big  superfamily of GST   controls  (72%).  Individuals  with  GSTM1  null/GSTT1
             genes  codes  cytosolic  enzymes,  the  most  common    active genotype carried 8 times higher risk of RCC than
             members of cytosolic GST are families (classes): alpha   those with GSTM1 active/GSTT1 null genotype. GSTM1
             (GSTA), mu (GSTM), pi (GSTP) and theta (GSTT). (3)      and  GSTT1  genotypes  did  not  significantly  correlate
             Genetic polymorphism is present  in  this  whole  family,   with tumor grade, however, our results showed a higher
             but deletion polymorphisms in classes GSTM1 i GSTT1     proportion  of  higher  tumor  grade  in  subjects  with
             are  so  far  proven  to  be  the  most  significant  ones  for   GSTM1  null  and  GSTT1  active  genotypes,  both
             developing RCC. (4)                                     individually  and  combined.  Also,  there  was  no
                                                                     significant  difference  between  patients  with  RCC  and

          2.  The aim of the study research                          controls regarding sex distribution, body mass index and
                                                                     frequency of smoking. The risk of developing RCC was
                                                                     2 times higher in people with arterial hypertension than
             The aim of this study was to test the association between   in people with normal blood pressure.
             GSTM1 and GSTT1 polymorphism and susceptibility to
             develop clear RCC (cRCC).
                                                                  5.  Conclusion
          3.  Materials and methods of work
                                                                     According  to  our  results,  GSTM1  null  genotype  is
                                                                     statistically significantly associated with RCC risk, both
             A  hospital-based  case  control  study  recruited  98   individually  or  in  combination  with  GSTT1-active
             incidence cases and 240 sex and age-matched controls.   genotype,  as  well  as  with  slower  tumor  progression.
             A specially structured epidemiological survey was used   Additional studies with higher numbers of subjects are
             for  gathering  data  about  exposure  to  assumed      needed  to  confirm  and  extend  these  findings.
             environmental  risk  factors  for  developing  cancer.
             Histological  evaluation  was  performed  by  one    6.  Literature
             uropathologist  according  to  WHO  classification  of
             tumors  and  TNM  classification  system  for  tumor
             grading.  GSTM1  and  GSTT1  polymorphism  was          (1)  Hayes  JD,  Pulford  DJ.  The  Glutathione  S-
             determined by multiplex PCR.                            Transferase Supergene Family: Regulation of GST and
                                                                     the  Contribution  of  the  lsoenzymes  to  Cancer
                                                                     Chemoprotection and Drug Resistance Part II.
                                                                     (2)Ketterer  B.  Protective  role  of  glutathione  and
                                                                     glutathione   transferases   in   mutagenesis   and
                                                                     carcinogenesis.
                                                                     (3)  Mannervik  B,  Wildersten  M.  Human  glutathione
                                                                     transferases: classification, tissue distribution,  structure
                                                                     and functional properties.
                                                                     (4) Howells RE, Holland T, Dhar KK, et al. Glutathione
                                                                     S-transferase GSTM1 and GSTT1 genotypes in ovarian
                                                                     cancer:  association  with  p53  expression  and  survival


           Figure 1- A representative image of multiplex PCR analysis
                  of GSTM1 and GSTT1 gene polymorphisms
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