Single nucleotide polypmorphisms in ERCC1 are associated with disease progression, and survival in patients with advanced stage ovarian and primary peritoneal carcinoma; A Gynecologic Oncology Group Study

Objective: This study evaluated common polymorphisms in excision repair cross-complementation group 1 (ERCC1) involved in repair of platinum-induced DNA damage in advanced-stage, epithelial ovarian/peritoneal/tubal cancer (EOC/PPC/FTC) patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy. Methods: Pyrosequencing was performed to examine single nucleotide polymorphisms (SNPs) in codon 118 and C8092A in ERCC1 in leukocyte DNA from the Gynecologic Oncology Group phase III protocol, GOG-182. Kaplan-Meier method and adjusted Cox regression modeling were used to examine associations between ERCC1 polymorphisms and progression-free survival (PFS) and overall survival (OS). Results: The genotype distribution at codon 118 (n = 278) in ERCC1 for CC, CT, and TT was 23%, 45% and 32%, and the median OS was 32, 47 and 43 months, respectively. Patients with the CT + TT versus CC genotype in codon 118 in ERCC1 were at a reduced risk of death (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.49-0.95, p = 0.025). The genotype distribution for C8092A in ERCC1 (N = 280) was 50%, 42% and 8%, and the median OS was 45, 40 or 30 months for CC, CA and AA, respectively. Women with the CA + AA versus CC genotype in C8092A in ERCC1 had a trend suggesting an increased risk of death (HR = 1.29, 95% CI = 0.97-1.72, p = 0.077). Conclusions: The polymorphism in codon 118 in the DNA repair gene ERCC1 was an independent predictor for better survival in EOC/PPC/FTC patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy. The relationship between the C8092A polymorphisms in ERCC1 and survival was modest with an effect size that was not always statistically significant.