[Polymorphisms of ERCC1 gene and outcomes in epithelial ovarian cancer patients with platinum-based chemotherapy]

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 rs11615 SNP of ERCC1 may become a valuable prognostic biomarker for EOC patients treated with platinum-based chemotherapy.