%0 Generic
%A Gerola, Stefano
%C Heidelberg
%D 2013
%F heidok:14945
%R 10.11588/heidok.00014945
%T Association of genetic variants of apoptosis related genes with early colorectal tumor lesions
%U https://archiv.ub.uni-heidelberg.de/volltextserver/14945/
%X Deregulation  of  apoptosis  is  a  frequent  alteration  in  benign,  pre-­‐cancerous  lesions  of  the  colon  mucosa  that  has  been  extensively  discussed  as  contributor  to  the  development  of  colorectal  cancer.  Individual  differences  in  the  regulation  of  apoptosis  are  (epi-­‐)genetically  determined  and  identification  of  SNPs  within  coding/  flanking  regions  of  genes  with  apoptosis  relevant  function  could  provide  a  basis  to  assess  the  individual  risk  to  develop  these  lesions.  To  identify  a  possible  association  between  genetic  polymorphisms  and  tumorigenesis  we  selected  865  genes  with  reported  function  within  the  apoptosis  pathways  or  in  related  (e.g.  stress  related)  pathways.  Our  screening  was  performed  on  a  customized  goldengate  Illumina  chip  covering  1536  single  nucleotide  polymorphisms  in  a  two  stage  approach.  Stage  I  was  performed  on  272  patients  harboring  hyperplastic  polyps  and  512  controls.  Stage  II  aimed  to  validate  preliminary  data  by  screening  the  candidate  SNPs  (p<0.01)  on  an  independent  cohort  of  patients  and  controls  (n=76).  After  the  meta-­‐analysis  between  stage1  and  stage2  the  false  discovery  rate  (FDR)  approach  has  been  used  to  calculate  the  “q”  of  significativity  in  order  to  have  a  better  compromise  between  Type1  and  Type2  errors.  Among  the  candidate  polymorphisms  9  SNPs  were  significantly  correlated  with  the  occurrence  of  hyperplastic  polyps.  Out  of  these  the  variation  rs4709583  (PARK2)  presented  the  highest  significativity  level  (q=0.003)  and  was  therefore  further  analysed  in-­‐vitro  to  identify  its  potential  influence  on  splicing  in  the  PARK2  gene.