ERCC1 codon 118 C→T polymorphism associated with ERCC1 expression and outcome of FOLFOX-4 treatment in Asian patients with metastatic colorectal carcinoma.
We analyzed the influence of codon 118 C→T polymorphism of ERCC1 on its protein expression levels, clinicopathological features, and outcome of 168 Chinese patients with metastatic colorectal carcinoma that had been treated with first-line FOLFOX-4 chemotherapy. A high prevalence of C/C genotype was noted (47.6%, n = 80; 168 patients in total). A marked increase of ERCC1 protein expression levels was also noted in patients with C/T or T/T genotypes (70%vs 20%; P < 0.01), which was associated with significantly lower response to FOLFOX-4 (36.4%vs 57.5%; p = 0.01), and shorter progression-free (7 months vs 13 months; P < 0.01) and overall (16 months vs 25 months; P < 0.01) survival times. By multivariate analysis, this polymorphism was also identified as an independent prognostic factor (P = 0.02). These data suggest that Asian populations have a significantly higher prevalence of the C/C genotype in ERCC1 codon 118, which could be a key determinant for good responses to oxaliplatin-based treatment and favorable outcomes.
Chang
Peter Mu-Hsin
PM
School of Medicine, National Yang-Ming University School of Medicine, No. 155 Sec. 2 Linong Street, Taipei, Taiwan.
Tzeng
Cheng-Hwai
CH
Chen
Po-Min
PM
Lin
Jen-Kou
JK
Lin
Tzu-Chen
TC
Chen
Wei-Shone
WS
Jiang
Jeng-Kae
JK
Wang
Huann-Sheng
HS
Wang
Wei-Shu
WS
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics*; D003062:Codon / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007124:Immunoenzyme Techniques; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics*; D015996:Survival Rate; D016896:Treatment Outcome
D003062:Codon; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; C071447:ERCC1 protein, human; D004720:Endonucleases; D002955:Leucovorin; D005472:Fluorouracil