Department of Obstetrics and Gynecology, College of Public Health University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Gynecol Oncol. 2013 Aug;130(2):377-82. doi: 10.1016/j.ygyno.2013.04.054. Epub 2013 Apr 28.
This study aims to assess the role of polymorphisms in DNA repair genes, excision repair cross-complementation group 1 (ERCC1) and methyl-methanesulfonate sensitivity 19 (MMS19), in tumor response to platinum-based chemotherapy and survival in advanced epithelial ovarian cancer (EOC).
Single nucleotide polymorphism (SNP) analysis was performed on the paraffin-embedded tumor tissue of women with advanced EOC, treated with platinum-based chemotherapy at the University of Oklahoma Health Sciences Center. Polymorphisms from two ERCC1 (codon-118 and C8092A) and three MMS19 (rs2211243, rs2236575 and rs872106) gene loci were evaluated by real time PCR Allelic Discrimination Assay.
Genotyping was performed in 107 patients, 45 platinum-sensitive and 62 platinum-resistant. ERCC1, codon-118 and C8092A genotyping was evaluable in 98 and 106 patients respectively and in all 107 patients for MMS19 polymorphisms. No differences were observed in genotype between platinum-sensitive and platinum-resistant patients. Polymorphisms in the ERCC1, codon-118 and MMS19 genes did not correlate with overall survival (OS), although a trend toward improved progression free survival (PFS) was observed in patients expressing the minor (GG) alleles of the rs872106 MMS19 gene. Women homozygous for the ERCC1-C8092A minor (AA) alleles had a significant increase in PFS compared to AC and CC patients and both AA and AC genotypes conferred improved survival over the major (CC) genotype.
Polymorphisms in ERCC1, codon-118 and MMS19 genes are not associated with clinical response to platinum or survival. The ERCC1-C8092A genotypes containing an "A" allele were associated with significant improvement in PFS and OS strengthening the value of this specific genotype in survival.
本研究旨在评估 DNA 修复基因切除修复交叉互补组 1（ERCC1）和甲磺酸甲酯敏感性 19（MMS19）中的多态性在铂类化疗治疗晚期上皮性卵巢癌（EOC）中的肿瘤反应和生存中的作用。
在俄克拉荷马大学健康科学中心接受铂类化疗治疗的晚期 EOC 女性的石蜡包埋肿瘤组织上进行单核苷酸多态性（SNP）分析。通过实时 PCR 等位基因鉴别分析评估来自两个 ERCC1（密码子 118 和 C8092A）和三个 MMS19（rs2211243、rs2236575 和 rs872106）基因座的多态性。
对 107 例患者进行了基因分型，其中 45 例为铂类敏感型，62 例为铂类耐药型。对 ERCC1、密码子 118 和 C8092A 基因分型可评估的患者分别为 98 例和 106 例，107 例患者均可评估 MMS19 多态性。铂类敏感型和铂类耐药型患者的基因型无差异。尽管观察到 rs872106 MMS19 基因的次要（GG）等位基因表达的患者无进展生存期（PFS）有改善趋势，但 ERCC1、密码子 118 和 MMS19 基因的多态性与总生存期（OS）无关。ERCC1-C8092A 次要（AA）等位基因纯合的女性与 AC 和 CC 患者相比，PFS 显著增加，并且 AA 和 AC 基因型的生存均优于主要（CC）基因型。
ERCC1、密码子 118 和 MMS19 基因的多态性与铂类治疗的临床反应或生存无关。含有“ A”等位基因的 ERCC1-C8092A 基因型与 PFS 和 OS 的显著改善相关，这加强了该特定基因型在生存中的价值。
