Toxicity and therapy outcome associations in LIG3, SLCO1B3, ABCB1, OPRM1, and GSTP1 in high-grade serous ovarian cancer.

Adverse effects are the major limiting factor in combinatorial chemotherapies. To identify genetic associations in ovarian cancer chemotherapy-induced toxicities and therapy outcomes, we examined a cohort of 101 patients receiving carboplatin-paclitaxel treatment with advanced high-grade serous ovarian cancers. Based on literature and database searches, we selected 19 candidate polymorphisms, designed a multiplex single nucleotide polymorphism-genotyping assay, and applied Cox regression analysis, case-control association statistics, and the log-rank Mantel-Cox test. In the Cox regression analysis, the SLCO1B3 rs1052536 AA-genotype was associated with a reduced risk of any severe toxicity (hazard ratio = 0.35, p=0.023). In chi-square allelic test, the LIG3 rs1052536 T-allele was associated with an increased risk of neuropathy (odds ratio (OR) = 2.79, p=0.031) and GSTP1 rs1695 G-allele with a poorer response in the first-line chemotherapy (OR=2.65, p=0.026). In Kaplan-Meier survival analysis, ABCB1 rs2032582 TT-genotype was associated with shorter overall survival (uncorrected p=0.025), and OPRM1 rs544093 GG and GT genotypes with shorter platinum-free interval (uncorrected p=0.027) and progression-free survival (uncorrected p=0.012). Results suggest that SLCO1B3 and LIG3 variants are associated with the risk of adverse effects in patients receiving carboplatin-paclitaxel treatment, the GSTP1 variant may affect the treatment response, and ABCB1 and OPRM1 variants may influence the prognosis.