ERCC1 and XRCC1 Gene Polymorphisms Predict Response to Neoadjuvant Radiochemotherapy in Esophageal Cancer

作者：Warnecke Eberz Ute^*; Vallboehmer Daniel; Alakus Hakan; Kuetting Fabian; Lurje Georg; Bollschweiler Elfriede; Wienand Dorweiler Anke; Drebber Uta; Hoelscher Arnulf H; Metzger Ralf

来源：Journal of Gastrointestinal Surgery, 2009, 13(8): 1411-1421.

DOI：10.1007/s11605-009-0881-z

• Single-nucleotide polymorphism
• Nucleotide excision repair
• Multimodality treatment
• Chemo-radio-sensitivity
• Response prediction

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.
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.
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.
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.

• 出版日期2009-8