Polymorphisms in XPD and ERCC1 Associated with Colorectal Cancer Outcome
1
Department of Radiation Oncology, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
2
Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
3
Division of Gastrointestinal and General Surgery, Department of Surgery, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
4
Department of Surgery, Faculty of Medicine, Graduate Institute of Medicine, Kaohsiung 807, Taiwan
5
Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
6
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
7
Division of Colorectal Surgery, Department of Surgery, ZuoYing Armed Forces General Hospital, Kaohsiung 813, Taiwan
8
School of Medical and Health Science, Fooyin University, Kaohsiung Hsien 831, Taiwan
9
Department of Medical Research, Fooyin University Hospital, Pingtung County 928, Taiwan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2013, 14(2), 4121-4134; https://doi.org/10.3390/ijms14024121
Received: 9 November 2012 / Revised: 9 December 2012 / Accepted: 25 January 2013 / Published: 19 February 2013
(This article belongs to the Special Issue Pathogenesis and Prevention of Colorectal Cancer)
Using the comprehensive approach to selecting polymorphisms to date, we sought to examine whether recurrence in colorectal cancer was associated with inherited variation in three genes involved in DNA repair and cell proliferation. Three polymorphisms, which are excision repair cross-complementation 1 (ERCC1), xeroderma pigmentosum group D (XPD) and epidermal growth factor receptor (EGFR), were assessed in 257 postoperative stage II/III CRC patients with 5-fluorouracial chemotherapy in Taiwan. In addition, the correlations between genetic polymorphisms and patients’ clinicopathological features were investigated. Genotypes of XPD codon751 A/A and ERCC1 codon118 T/T were associated with regional recurrence in a statistically significant way (p = 0.018). Patients who carried XPD AA and ERCC1 TT genotypes demonstrated a significantly greater regional recurrence risk (OR = 5.625, 95% CI, 1.557–20.32). Inherited variation in XPD and ERCC1 was associated with outcome in patients with colorectal cancer in Taiwan. As the significant association of single-nucleotide polymorphisms has not been studied previously in colorectal cancer, these findings suggest novel sites of variation, in part explaining the range of treatment responses seen in this disease.
Keywords:
genetic polymorphism; XPD; ERCC1; colorectal cancer; regional recurrence