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.
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).
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).
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.
Departments of aRadiation Oncology
cDivision of Gastrointestinal and General Surgery, Department of Surgery
dDivision of Gastroenterology, Department of Internal Medicine
eDivision of Hepatobiliary Surgery, Department of Surgery
fCancer Center, Kaohsiung Medical University Hospital
Departments of gRadiation Oncology
hInternal Medicine, Faculty of Medicine
jSurgery, Faculty of Medicine
lGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University
mDivision of Proctology, Department of Surgery, ZuoYing Armed Forces General Hospital, Kaohsiung
nDepartment of Surgery, Chi-Mei Medical Center, Tainan
oSchool of Medical and Health Sciences, Fooyin University
pDepartment of Medical Research, Fooyin University Hospital, Pingtung, Taiwan
Correspondence to Jaw-Yuan Wang, MD, PhD, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan Tel: +886 7 3122805; fax: +886 7 3114679; e-mail: firstname.lastname@example.org
Received June 10, 2010
Accepted October 6, 2010