title: Polymorphism in epidermal growth factor receptor intron 1 predicts prognosis of patients with esophageal cancer after chemoradiation and surgery.
abstract: BACKGROUND
  The EGFR gene has been demonstrated to be an important factor influencing treatment response for various cancers, and its expression has been shown to be modified by the polymorphic CA repeat length at the 5'-regulatory sequence in intron 1. We investigated whether this EGFR polymorphism is associated with prognosis in patients with esophageal cancer after concurrent chemoradiotherapy (CCRT) and esophagectomy.
  
  
  METHODS
  A cohort of 148 patients with esophageal cancer received cisplatin-based CCRT (concurrently combined with 40 Gy irradiation) and subsequent esophagectomy. Their EGFR genotypes were determined by polymerase chain reaction from leukocyte DNA, which was obtained before treatment and was correlated with patient survival.
  
  
  RESULTS
  Patients with the homozygous short allele (<20 CA) of the EGFR gene in intron 1 were more likely to have a shorter duration of survival after CCRT and surgery than those with the homozygous long allele [adjusted hazard ratio (HR) (95% confidence interval [CI]) of death: 1.88 (1.02-3.49); P = 0.045]. This unfavorable prognostic effect of EGFR homozygous short CA repeat was mainly manifested in patients with good response to CCRT [adjusted HR (95% CI) of death 3.40 (1.06-10.89); P = 0.039]; it was less evident in those with poor response to CCRT [adjusted HR (95% CI) 1.40 (0.65-3.02); P = 0.384].
  
  
  CONCLUSIONS
  The EGFR CA repeat genetic polymorphism may act as a valuable molecular predictor of clinical outcome of esophageal cancer after CCRT and esophagectomy, especially in those with good response to CCRT.
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. ntuhlee@yahoo.com
authors.forename: Jang-Ming
authors.initials: JM
authors.lastname: Lee
authors.forename: Shi-Yi
authors.initials: SY
authors.lastname: Yang
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Yang
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.forename: Ming-Tsang
authors.initials: MT
authors.lastname: Wu
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lin
authors.forename: Jason Chia-Hsien
authors.initials: JC
authors.lastname: Cheng
authors.forename: Ying-Hao
authors.initials: YH
authors.lastname: Wang
authors.forename: Tzu-Hsuen
authors.initials: TH
authors.lastname: Chuang
authors.forename: Jin-Shing
authors.initials: JS
authors.lastname: Chen
authors.forename: Hsao-Hsun
authors.initials: HH
authors.lastname: Hsu
authors.forename: Pei-Ming
authors.initials: PM
authors.lastname: Huang
authors.forename: Shuenn-Wen
authors.initials: SW
authors.lastname: Kuo
authors.forename: Yung-Chie
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001918:Brachytherapy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007438:Introns / Q000235:genetics*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000628:therapy; D017239:Paclitaxel / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; C512478:EGFR protein, human; D066246:ErbB Receptors; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil