ABSTRACT
Objective To explore the relationship among single nucleotide polymorphism (SNP) of excision repair cross-complementing 1 (ERCC1) gene,chemotherapy sensitivity and clinical outcomes of epithelial ovarian cancer (EOC) patients treated with platinum.Methods Six tag single nucleotide polymorphisms (tagSNP;rs11615,rs3212986,rs735482,rs3212955,rs12610134 and rs3212958) were chose from ERCC1 gene.The genotypes of 6 tagSNP were determined by Snapshot method in 220 EOC patients.Primary clinical outcomes parameter contained EOC patients'responses to platinum-based chemotherapy,progression-free survival (PFS) and overall survival (OS) were analysed.Results The rs11615 C/T SNP of ERCC1,CC,CT and TT genotype frequencies were 53.1％,45.6％,1.4％ in responders to platinum-based chemotherapy,while 52.0％,35.6％,12.3％ in non-responders,respectively,in which there was significant difference between the two groups(P =0.002).Compared with the patients with CC genotype,the patients carrying TT genotype had a significantly poor response to platinum-based chemotherapy (OR =6.22,95％ CI:1.12-34.42).Similarly,the genotypes frequencies distribution of rs11615 C/T SNP of ERCC1 was different between the recurrence and non-recurrence group,death and survival group (all P ＜ 0.05).Kaplan-Meier survival analysis showed that the genotypes frequencies distribution of rs11615 C/T SNP of ERCC1 was associated with PFS and OS(P ＜ 0.01) of EOC patients.Cox's multivariate analysis suggested that patients with TT genotype had a shorter PFS (HR =2.19,95 ％ CI:1.14-4.22,P =0.009) and OS (HR =2.22,95 ％ CI:1.06-4.64,P =0.021) compared with those carrying CC genotype [adjusting for age,International Federation of Gynecology and Obstetrics (FIGO) stage,pathological type,grade and tumor residual size].The genotypes frequencies distribution of rs3212986,rs735482,rs3212955,rs12610134 and rs3212958 SNP of ERCC1 did not show the significant difference between the responders to platinum-based chemotherapy and non-responders.The other 5 tagSNP may not be associated with the PFS and OS of EOC patients (all P ＞ 0.05).Conclusion The rs 11615 SNP of ERCC1 may become a valuable prognostic biomarker for EOC patients treated with platinum-based chemotherapy.