Multiple genetic polymorphisms in the prediction of clinical outcome of metastatic colorectal cancer patients treated with first-line FOLFOX-4 chemotherapy.
OBJECTIVE
The objective of the study is to investigate whether multiple chemotherapeutic agent-related genetic polymorphisms are associated with the clinical outcomes of Taiwanese metastatic colorectal cancers (mCRC) patients treated with the first-line FOLFOX-4 chemotherapy.


METHODS
Consecutive mCRC patients were prospectively enrolled into this study. Peripheral blood samples were used for genotyping of polymorphisms in MTHFR, DPD, GSTP1, MDR1, TYMS, ERCC1, XRCC1, and ERCC2 genes by polymerase chain reaction-restriction fragment length polymorphism technique and DNA sequencing. The primary end point of the study was to investigate the association of each genetic polymorphism with progression-free survival and overall survival (OS).


RESULTS
Favorable genotypes from polymorphisms in ERCC1 codon 118C/C [hazard ratio (HR)=0.061, 95% confidence interval (CI): 0.014-0.274, P<0.001] and XRCC1 codon 399G/G (HR=0.306, 95% CI: 0.103-0.905, P=0.032) that are associated with progression-free survival were identified. Furthermore, ERCC1 codon 118C/C (HR=0.065, 95% CI: 0.011-0.377, P=0.002) and XRCC1 codon 399G/G (HR=0.152, 95% CI: 0.041-0.568, P=0.005) were significantly associated with favorable OS. Combining ERCC1 and XRCC1 genetic polymorphisms, patients with both favorable genotypes of ERCC1 codon 118C/C and XRCC1 codon 399G/G were associated with the better OS than those with one or without any favorable genotypes (P<0.001).


CONCLUSIONS
The genetic polymorphisms of ERCC1 and XRCC1 may be useful in predicting clinical outcome in Taiwanese mCRC patients treated with FOLFOX-4. However, further prospective studies will be needed for the potential clinical implication.
Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan.
Ming-Yii
MY
Huang
Meng-Lin
ML
Huang
Ming-Jenn
MJ
Chen
Chien-Yu
CY
Lu
Chin-Fan
CF
Chen
Pei-Chien
PC
Tsai
Shih-Chang
SC
Chuang
Ming-Feng
MF
Hou
Shiu-Ru
SR
Lin
Jaw-Yuan
JY
Wang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D056726:Genetic Association Studies; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000502:physiology; D011379:Prognosis; D013624:Taiwan; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil