ERCC1 and XRCC1 gene polymorphisms predict response to neoadjuvant radiochemotherapy in esophageal cancer.
BACKGROUND
Neoadjuvant treatment strategies have been developed to improve survival of patients with locally advanced esophageal cancer. Since only patients with major histopathological response benefit from this therapy, predictive markers are needed. We examined a panel of selected gene polymorphisms to predict response to neoadjuvant radiochemotherapy (cisplatin, 5-fluorouracil, 36 Gy) in esophageal cancer patients.


METHODS
Genomic DNA was extracted from paraffin-embedded tissues of 52 patients. Allelic genotyping was performed by real-time polymerase chain reaction using allele-specific TaqMan probes and correlated with therapy response.


RESULTS
Single-nucleotide polymorphism ERCC1 C118T was predictive for therapy response (p < 0.003). Within the TT genotype group of 25 patients, 20 (80%) did not respond to chemoradiation. Of 20 patients with heterogeneous C/T genotype, 14 (70%) were major responders. The CC genotype (seven patients) was not of predictive importance. ERCC1 polymorphism was significantly (p < 0.02) associated with formation of lymph node metastases. Predominant GG genotype of XRCC1 A194G was not predictive; however, the rarely occurring AA genotype was response-associated and the A/G variant was associated with nonresponse. Fifteen additionally analyzed polymorphisms did not show any correlation.


CONCLUSIONS
Our data support the role of ERCC1 as a predictive marker for therapy response. Single-nucleotide polymorphisms of ERCC1 and XRCC1 could be applied to further individualize treatment strategies.
Department of General, Visceral, and Cancer Surgery, Center for Integrated Oncology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany. ute.warnecke-eberz@uk-koeln.de
Ute
U
Warnecke-Eberz
Daniel
D
Vallböhmer
Hakan
H
Alakus
Fabian
F
Kütting
Georg
G
Lurje
Elfriede
E
Bollschweiler
Anke
A
Wienand-Dorweiler
Uta
U
Drebber
Arnulf H
AH
Hölscher
Ralf
R
Metzger
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011110:Polymorphism, Genetic; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D000076105:X-ray Repair Cross Complementing Protein 1
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C071447:ERCC1 protein, human; D004720:Endonucleases