ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study

Six gene polymorphisms functional in drug-metabolism – GSTP1 Ile105Val, ABCB1 Ile1145Ile, MTHFR Ala222Val, TYMS double (2R) or triple (3R) tandem repeat – and DNA-repair genes – ERCC2 Lys751Gln and XRCC1 Arg399Gln – were assessed in 201 CRC patients using a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique and DNA sequencing. Patients were diagnosed as either high-risk stage II (T2 and 3 N0 M0) or III (any T N1 and 2 M0) and were administered adjuvant chemotherapy regimens that included 5-fluorouracil (5FU) and leucovorin (LV). The correlations between genetic polymorphisms and patient clinicopathological features and relapses were investigated.In this study, the distributions of GSTP1 (P = 0.003), ABCB1 (P = 0.001), TYMS (P < 0.0001), ERCC2 (P < 0.0001) and XRCC1 (P = 0.006) genotypes in the Asian population, with the exception of MTHFR (P = 0.081), differed significantly from their distributions in a Caucasian population. However, the unfavorable genotype ERCC2 2251A>C (P = 0.006), tumor invasion depth (P = 0.025), lymph node metastasis (P = 0.011) and cancer stage (P = 0.008) were significantly correlated with early relapse. Patients carrying the ERCC2 2251AC or2251CC genotypes had a significantly increased risk of early relapse (OR = 3.294, 95% CI, 1.272–8.532).We suggest that ERCC2 2251A>C alleles may be genetic predictors of early CRC relapse.The primary treatment for colorectal cancer (CRC) is resection of the primary tumor. After surgery, patients are frequently administered adjuvant chemotherapy to eliminate cancer cells that may have metastasized [1]. Despite chemotherapy, CRC remains the third major cause of cancer-related death in Taiwan, accounting for >3,000 deaths per year [2]. The overall five-year survival is 50–60% in European countries [3], a result similar to that in Taiwan [4]. The primary cause of death is distant and loco-regional relapses. Notably, CRC relapse is strongly correlated with chemotherapeutic