Correlation between SNPs of XPD751, XPD312 and chemotherapeutic efficacy in colorectal carcinoma patients

Objective: To investigate the correlation between single nucleotide polymorphisms (SNPs) of XPD751, XPD312 and the sensitivity of FOLFOX regimen in the patients with advanced colorectal cancer (CRC), and evaluate the SNPs of the two on the prognosis in advanced CRC. Methods: 88 patients were diagnosed as advanced CRC by CT scan. Blood routine, liver function and electrocardiogram (ECG) examinations were carried on before chemotherapy. The patients were with score of 1~2 according to Eastern Cooperative Oncology Group (ECOG). The blood sample was collected from each patient before treating with FLOFOX. All the 88 patients were treated with FLOFOX. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the SNPs in XPD751 and XPD312. The correlation between different genotypes and the prognosis of FOLFOX was analyzed. Results: 1 In XPD751, there were 61 cases with Lys/Lys (69.3%), 55 as DRC (90.2%), while 27 cases with Lys/Gln + Gln/Gln (30.7%), 18 as DRC (66.7%). There was significant difference on chemotherapeutic efficacy between the two (X2=5.601, P=0.037). In XPD312, there were 50 cases with Asp/Asp (56.8%), 33 as DRC (66.0%), while 38 cases with Asp/Asn + Asn/Asn (43.2%), 34 as DRC (89.5%). There was no significant difference on chemotherapeutic efficacy between the two (X2=2.388, P=0.067). The sensitivity to FOLFOX in the patients with Lys/Lys was 2.8 times as those with Lys/Gln + Gln/Gln (OR=2.815, P<0.05. 2 There was difference between the PFS in patients with Lys/ Lys (9.85 months) and those with Lys/Gln + Gln/Gln (8.03 months), significantly (X2=12.376, P<0.05). There was no significant difference between the PFS in the patients with Asp/Asp (10.04 months) and those with Asp/Asn + Asn/ Asn (8.50 months) (X2=13.690, P<0.05). 3 The PFS of the patients with Lys/Lys in XPD751 combined with Asp/ Asp in XPD312 was 13.08 months, the patients with Lys/Lys combined with Asp/Asn + Asn/Asn was 8.60 months, the patients with Lys/Gln + Gln/Gln combined with Asp/Asp was 7.93 months, and the patients with Lys/Gln + Gln/ Gln combined with Asp/Asn + Asn/Asn was 7.33 months. Comparing the PFS of the 4 mentioned above, there was significant difference (X2=13.690, P<0.05). 4 COX regression analysis showed that in sex, age, metastasis and the 4 genotypes, only the XPD751 Lys/Lys combined with XPD312 Asp/Asp was related to PFS, significantly (P<0.05, RR=0.308). 6 The major adverse reaction presented as myelosuppression, without significant difference comparing the SNPs between in XPD751 or in XPD312, including leukopenia or thrombocytopenia mainly in grade I or grade II, anemia mainly in grade I, nausea and vomiting mainly in grade II, liver injury mainly in grade I, peripheral nerve injury mainly in grade II. Conclusions: XPD751 SNPs was the prognostic factor related to the sensitivity to FOLFOX in patients with advanced CRC, while XPD312 SNPs was not. The patients with wile type of XPD751 or XPD312 were more sensitive to FOLFOX.