title: Prediction of response to chemoradiation in rectal cancer by a gene polymorphism in the epidermal growth factor receptor promoter region.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) has been associated with radioresistance in solid tumors. Recently a polymorphism in the Sp1 recognition site of the EGFR promoter region was identified. The present study investigated the predictive value of this polymorphism for the outcome of chemoradiation in locally advanced rectal cancer.
  
  
  METHODS
  The study included 77 patients with locally advanced T3 rectal tumors. Treatment consisted of preoperative radiation therapy at a total tumor dose of 65 Gy and concomitant chemotherapy with Uftoral. Blood samples from 63 patients were evaluated for Sp1 -216 G/T polymorphism by polymerase chain reaction analysis. Forty-eight primary tumor biopsies were available for EGFR immunostaining. Patients underwent surgery 8 weeks after treatment. Pathologic response evaluation was performed according to the tumor regression grade (TRG) system.
  
  
  RESULTS
  Forty-nine percent had major response (TRG1-2) and 51% moderate response (TRG 3-4) to chemoradiation. The rates of major response were 34% (10/29) in GG homozygote patients compared with 65% (22/34) in patients with T containing variants (p=0.023). Fifty-eight percent of biopsies were positive for EGFR expression (28/48). The major response rates with regard to EGFR immunostaining were not significantly different. EGFR-positive tumors were found in 83% of the GG homozygote patients compared with 38% of patients with TT or GT variants (p=0.008).
  
  
  CONCLUSIONS
  There was a significant correlation between EGFR Sp1 -216 G/T polymorphism and treatment response to chemoradiation in locally advanced rectal cancer. Further investigations of a second set of patient and other treatment schedules are warranted.
authors.affiliation: Department of Oncology, Danish Colorectal Cancer Group South, Vejle Hospital, University of Southern Denmark, Vejle, Denmark. kalgsp@vgs.vejleamt.dk
authors.forename: Karen-Lise Garm
authors.initials: KL
authors.lastname: Spindler
authors.forename: Jens Nederby
authors.initials: JN
authors.lastname: Nielsen
authors.forename: Jan
authors.initials: J
authors.lastname: Lindebjerg
authors.forename: Ivan
authors.initials: I
authors.lastname: Brandslund
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
mesh_terms: D000368:Aged; D003131:Combined Modality Therapy / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012004:Rectal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; D066246:ErbB Receptors