title: Epidermal growth factor receptor gene polymorphisms predict pelvic recurrence in patients with rectal cancer treated with chemoradiation.
abstract: An association between epidermal growth factor receptor (EGFR) signaling pathway and response of cancer cells to ionizing radiation has been reported. Recently, a polymorphic variant in the EGFR gene that leads to an arginine-to-lysine substitution in the extracellular domain at codon 497 within subdomain IV of EGFR has been identified. The variant EGFR (HER-1 497K) may lead to attenuation in ligand binding, growth stimulation, tyrosine kinase activation, and induction of proto-oncogenes myc, fos, and jun. A (CA)(n) repeat polymorphism in intron 1 of the EGFR gene that alters EGFR expression in vitro and in vivo has also been described. In the current pilot study, we assessed both polymorphisms in 59 patients with locally advanced rectal cancer treated with adjuvant or neoadjuvant chemoradiation therapy using PCR-RFLP and a 5'-end [gamma-(33)P]ATP-labeled PCR protocol. We tested whether either polymorphism alone or in combination can be associated with local recurrence in the setting of chemoradiation treatment. We found that patients with HER-1 497 Arg/Arg genotype or lower number of CA repeats (both alleles <20) tended to have a higher risk of local recurrence (P = 0.24 and 0.31, respectively). Combined analysis showed the highest risk for local recurrence was seen in patients who possessed both a HER-1 497 Arg allele and <20 CA repeats (P = 0.05, log-rank test). Our data suggest that the HER-1 R497K and EGFR intron 1 (CA)(n) repeat polymorphisms may be potential indicators of radiosensitivity in patients with rectal cancer treated with chemoradiation.
authors.affiliation: Division of Medical Oncology and Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: Wu
authors.initials: W
authors.lastname: Zhang
authors.forename: David J
authors.initials: DJ
authors.lastname: Park
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
authors.forename: Dong Yun
authors.initials: DY
authors.lastname: Yang
authors.forename: Michael
authors.initials: M
authors.lastname: Gordon
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.forename: Jim
authors.initials: J
authors.lastname: Yun
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Press
authors.forename: Daniel
authors.initials: D
authors.lastname: Vallböhmer
authors.forename: Katrin
authors.initials: K
authors.lastname: Rhodes
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D029742:Caenorhabditis elegans Proteins; D017024:Chemotherapy, Adjuvant; D004273:DNA, Neoplasm; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D029742:Caenorhabditis elegans Proteins; D004273:DNA, Neoplasm; C079744:her-1 protein, C elegans; D066246:ErbB Receptors; D005472:Fluorouracil