The combination of ERCC1 and XRCC1 gene polymorphisms better predicts clinical outcome to oxaliplatin-based chemotherapy in metastatic colorectal cancer.
OBJECTIVE
To evaluate the effect of excision repair cross-complementing group 1 (ERCC1) and X-ray cross-complementing group 1 (XRCC1) gene polymorphisms on treatment outcome in patients receiving oxaliplatin-based regimens for metastatic colorectal cancer.


METHODS
Hundred and thirteen patients with a diagnosis of metastatic colorectal cancer were treated with oxaliplatin-based chemotherapy. ERCC1 codon 118C/T and XRCC1 codon 399A/G polymorphisms were tested by real-time polymerase chain reaction (RT-PCR) method in peripheral blood lymphocytes of these patients. Disease control rates and survivals were compared by types of genotypes.


RESULTS
Analyses of the patterns of the polymorphism located at ERCC1 codon 118 showed that 55 (48.67%) patients were homozygous for C/C genotype, 15 (13.27%) were homozygous for the T/T genotype, and 43 (38.06%) were heterozygous for C/T genotype. Analyses of the polymorphism located at XRCC1 codon 399 showed that 61 (53.98%) patients were homozygous for A/A genotype, 13 (11.50%) were homozygous for the G/G genotype, and 39 (34.52%) were heterozygous for A/G genotype. After two cycles of chemotherapy, there was complete response (CR) in 1 patient, partial response (PR) in 24 patients, and stable disease (SD) in 56 patients. Altogether in 81 (71.68%) patients the disease was controlled after chemotherapy. Thirty-two (28.32%) patients showed disease progression. After adjusting for some clinical factors, both the ERCC1 polymorphism and the XRCC1 polymorphism lost their roles in predicting DCR (P = 0.662, P = 0.631) and MST (P = 0.692, P = 0.572). But the combination of ERCC1 and XRCC1 polymorphisms was significantly associated with DCR (P = 0.01) and MST (P = 0.000) independently.


CONCLUSIONS
This is the first study which showed that polymorphisms of ERCC1 and XRCC1, in combination not individually, were independent predictors for DCR and OS. This may contribute to the selection of patients who would benefit from oxaliplatin-based chemotherapy for metastatic colorectal cancer.
Liang
Jun
J
Department of Oncology, The Affiliated Hospital of Medical College, Qing Dao University, 266003, Qingdao, China. liangjun1959@hotmail.com
Jiang
Tao
T
Yao
Ru-yong
RY
Liu
Zi-min
ZM
Lv
Hong-ying
HY
Qi
Wei-wei
WW
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003062:Codon; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1
D003062:Codon; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D000077150:Oxaliplatin; C071447:ERCC1 protein, human; D004720:Endonucleases