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Background  Early relapse in colorectal cancer (CRC) patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage) and poor response to chemotherapy. Several investigations have demonstrated that genetic polymorphisms in drug-targeted genes, metabolizing enzymes, and DNA-repairing enzymes are all strongly correlated with inter-individual differences in the efficacy and toxicity of many treatment regimens. This preliminary study attempts to identify the correlation between genetic polymorphisms and clinicopathological features of CRC, and evaluates the relationship between genetic polymorphisms and chemotherapeutic susceptibility of Taiwanese CRC patients. To our knowledge, this study discusses, for the first time, early cancer relapse and its indication by multiple genes.    Methods  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 A rg399Gln – 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.    Results  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).    Conclusion  We suggest that  ERCC2  2251A>C alleles may be genetic predictors of early CRC relapse.

bmc cancer

ERCC22251A&gt;C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study