在高级别浆液性卵巢癌中，LIG3、SLCO1B3、ABCB1、OPRM1和GSTP1与毒性和治疗结果存在关联。
Toxicity and therapy outcome associations in LIG3, SLCO1B3, ABCB1, OPRM1, and GSTP1 in high-grade serous ovarian cancer.
发表日期：2023 Mar 29
作者：
Feng Deng, Maren Laasik, Liina Salminen, Lauri Lapatto, Kaisa Huhtinen, Yilin Li, Sampsa Hautaniemi, Johanna Hynninen, Mikko Niemi, Rainer Lehtonen
来源：
BIOMEDICINE & PHARMACOTHERAPY
摘要：
不良反应是组合化疗的主要限制因素。为了在卡铂-紫杉醇治疗中发现卵巢癌化疗引起的毒性和治疗效果的遗传关联，我们检查了101名接受卡铂-紫杉醇治疗的高级别浆液性卵巢癌患者的队列。基于文献和数据库搜索，我们选择了19个候选多态性，设计了多重单核苷酸多态性基因分型检测，应用Cox回归分析、病例-对照关联统计和对数秩Mantel-Cox检验。在Cox回归分析中，SLCO1B3 rs1052536 AA基因型与任何严重毒性的风险降低相关（风险比=0.35，p=0.023）。在卡方等位基因检验中，LIG3 rs1052536 T等位基因与神经病变的风险增加有关（整体比率（OR）=2.79，p=0.031），而GSTP1 rs1695 G等位基因与一线化疗的反应较差有关（OR=2.65，p=0.026）。在Kaplan-Meier生存分析中，ABCB1 rs2032582 TT基因型与更短的总生存期有关（未校正p=0.025），而OPRM1 rs544093 GG和GT基因型与更短的铂类药物自由间隔（未校正p=0.027）和进展无病存活期（未校正p=0.012）有关。结果表明，SLCO1B3和LIG3变异体与接受卡铂-紫杉醇治疗患者的不良反应风险有关，而GSTP1变异体可能影响治疗反应，ABCB1和OPRM1变异体可能影响预后。本文受版权保护，所有权利保留。
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.This article is protected by copyright. All rights reserved.