title: The role of single nucleotide polymorphisms of the ERCC1 and MMS19 genes in predicting platinum-sensitivity, progression-free and overall survival in advanced epithelial ovarian cancer.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Obstetrics and Gynecology, College of Public Health University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Katherine-moxley@ouhsc.edu
authors: K M
authors: KM
authors: Moxley
authors: D M
authors: DM
authors: Benbrook
authors: L
authors: L
authors: Queimado
authors: R E
authors: RE
authors: Zuna
authors: D
authors: D
authors: Thompson
authors: M
authors: M
authors: McCumber
authors: P
authors: P
authors: Premkumar
authors: E
authors: E
authors: Thavathiru
authors: L
authors: L
authors: Hines
authors: K N
authors: KN
authors: Moore
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077216:Carcinoma, Ovarian Epithelial; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D010984:Platinum / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C416322:MMS19 protein, human; D014157:Transcription Factors; D010984:Platinum; C071447:ERCC1 protein, human; D004720:Endonucleases
keywords: ERCC1; Epithelial ovarian cancer; MMS19; Single nucleotide polymorphisms; Survival