胰岛素样生长因子2/ H19基因座的多态性与中国上皮性卵巢癌患者对铂类化疗的反应相关。

Polymorphisms in IGF2/H19 gene locus are associated with platinum-based chemotherapeutic response in Chinese patients with epithelial ovarian cancer.

作者信息

Zeng Ying, Li Tai-Lin, Zhang Hai-Bo, Deng Jun-Li, Zhang Rui, Sun Hong, Wan Zi-Rui, Liu Ying-Zi, Zhu Yuan-Shan, Wang Guo

机构信息

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China.

Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China.

出版信息

Pharmacogenomics. 2019 Feb;20(3):179-188. doi: 10.2217/pgs-2018-0153. Epub 2019 Jan 23.

DOI:10.2217/pgs-2018-0153

PMID:30672383

Abstract

AIM

The present study aimed to assess the association between IGF2/H19 genetic variants and susceptibility to platinum-based chemotherapy in epithelial ovarian cancer (EOC).

METHODS

A total of 43 platinum-resistant (PR) and 138 platinum-sensitive (PS) EOC patients were recruited in our study. 21 polymorphisms in IGF2/H19 locus were genotyped by Sequenom MassARRAY assay.

RESULTS

The frequencies of GG genotype in both rs3842761(C/G) and rs4244809(A/G) were significantly lower in PR group compared with those in PS group (9.76 vs 23.36%, p = 0.049; 9.76 vs 26.09%, p = 0.045; respectively). Compared with the AA genotype, rs4244809 GG genotype was associated with significantly reduced risk of platinum resistance (adjusted OR: 0.30; 95% CI: 0.10-0.91; p = 0.033). Further stratified analyses revealed that the SNPs of rs3842761 and rs4244809 were greatly related to PR risk in FIGO stage III-IV (rs3842761GG/CC+CG: adjusted OR: 0.15; 95% CI: 0.02-1.21; rs4244809 GG/AA+AG: adjusted OR: 0.24; 95% CI: 0.07-0.84; respectively) and serous adenocarcinoma subgroups (rs3842761 GG/CC+CG: adjusted OR: 0.21; 95% CI: 0.05-0.94; rs4244809 GG/AA+AG: adjusted OR: 0.19; 95% CI: 0.04-0.5; respectively), while rs7924316 polymorphism was associated with reduced risk of PR in serous adenocarcinoma subgroup as analyzed by a recessive model (rs7924316 GG/TT+TG: adjusted OR: 0.22; 95% CI: 0.05-0.98). In addition, both TCT haplotypes of rs3741206/rs3842761/rs7924316 and TC haplotype of rs3741206/rs3842761 were associated with elevated risk of PR (for the TCT haplotype of rs3741206/rs3842761/rs7924316: p = 0.049; OR: 1.69; 95% CI: 1.00-2.87; for the TC haplotype of rs3741206/rs3842761: p = 0.044; OR: 1.71; 95% CI: 1.01-2.88).

CONCLUSION

These results suggest that polymorphisms in IGF2/H19 gene locus are associated with PR risk in EOC.

摘要

目的

本研究旨在评估胰岛素样生长因子2（IGF2）/H19基因变异与上皮性卵巢癌（EOC）铂类化疗敏感性之间的关联。

方法

本研究共纳入43例铂类耐药（PR）和138例铂类敏感（PS）的EOC患者。采用Sequenom MassARRAY技术对IGF2/H19基因座的21个多态性位点进行基因分型。

结果

PR组中rs3842761（C/G）和rs4244809（A/G）的GG基因型频率显著低于PS组（分别为9.76%对23.36%，p = 0.049；9.76%对26.09%，p = 0.045）。与AA基因型相比，rs4244809的GG基因型与铂类耐药风险显著降低相关（校正比值比：0.30；95%置信区间：0.10 - 0.91；p = 0.033）。进一步分层分析显示，rs3842761和rs4244809的单核苷酸多态性（SNP）与国际妇产科联盟（FIGO）III - IV期的PR风险密切相关（rs3842761 GG/CC + CG：校正比值比：0.15；95%置信区间：0.02 - 1.21；rs4244809 GG/AA + AG：校正比值比：0.24；95%置信区间：0.07 - 0.84）以及浆液性腺癌亚组（rs3842761 GG/CC + CG：校正比值比：0.21；95%置信区间：0.05 - 0.94；rs4244809 GG/AA + AG：校正比值比：0.19；95%置信区间：0.04 - 0.5），而rs7924316多态性在隐性模型分析中与浆液性腺癌亚组的PR风险降低相关（rs7924316 GG/TT + TG：校正比值比：0.22；95%置信区间：0.05 - 0.98）。此外，rs3741206/rs3842761/rs7924316的TCT单倍型和rs3741206/rs3842761的TC单倍型均与PR风险升高相关（rs3741206/rs3842761/rs7924316的TCT单倍型：p = 0.049；比值比：1.69；95%置信区间：1.00 - 2.87；rs3741206/rs3842761的TC单倍型：p = 0.044；比值比：1.71；95%置信区间：1.01 - 2.88）。