Association of single nucleotide polymorphisms in the MVP gene with platinum resistance and survival in patients with epithelial ovarian cancer

• Published in: Oncology letters 2016-04, Vol.11 (4), p.2925-2933
• Main Authors: ZHAO, YA-NAN, HE, DONG-NING, WANG, YA-DI, LI, JUN-JIE, HA, MIN-WEN
• Format: Article
• Language: English
• Subjects: Cancer therapies; Chemotherapy; Confidence intervals; Deoxyribonucleic acid; Development and progression; DNA; Drug resistance; epithelial ovarian cancer; Genetic aspects; Haplotypes; Health aspects; Medical prognosis; Mortality; MVP; Oncology; Ovarian cancer; Patient outcomes; Platinum compounds; platinum resistance; Polymerase chain reaction; Proteins; single nucleotide polymorphism; Single nucleotide polymorphisms; Surgery; survival; Survival analysis; tetra-primer ARMS-PCR
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2016.4311

The human major vault protein (MVP) has been linked to the development of multidrug resistance in cancer cells, and overexpression of MVP has been observed in ovarian cancer tissues. The aim of the present study was to investigate the association between single nucleotide polymorphisms (SNPs) in the MVP gene and the tumor response to platinum-based chemotherapy and survival of patients affected by epithelial ovarian cancer (EOC), in addition to confirm whether tetra-primer amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) is an accurate genotyping method. For this purpose, two polymorphisms in the MVP gene, namely reference SNP (rs)1057451 and rs4788186, were selected from the data obtained by the International haplotype map (HapMap) Project regarding Chinese Han population, and were evaluated by tetra-primer ARMS-PCR. Upon validation by DNA sequencing, the association of these polymorphisms with platinum resistance, progression-free survival (PFS) and overall survival (OS) in patients with EOC was assessed. The results of tetra-primer ARMS-PCR were in agreement with those derived from DNA sequencing. No significant differences were observed between platinum-sensitive and platinum-resistant cohorts in terms of allele and genotype distribution of these two polymorphisms in the MVP gene, which were not associated with PFS or OS. However, a trend toward prolonged PFS was observed in patients carrying the heterozygous AG allele at the rs4788186 locus. These results suggest that rs1057451 and rs4788186 variants in the MVP gene are not associated with favorable therapeutic response to platinum or longer survival in Chinese Han patients affected by EOC. In addition, the data of the present study confirm that tetra-primer ARMS-PCR is a trustworthy and economical genotyping method.