Polymorphisms of ABCB1, CYP3A4 and CYP3A5 Genes in Ovarian Cancer and Treatment Response in Poles

Anticancer Res. 2018 Mar;38(3):1455-1459. doi: 10.21873/anticanres.12370.

Abstract

Background/aim: Ovarian cancer is a lethal gynecological malignancy, with 5-year survival of only about one third of patients. The ABCB1 gene encodes the P-glycoprotein which is one of the multidrug efflux pumps. Its decreased activity may result in multidrug resistance of cancer cells. Drug-metabolizing enzymes Cyp3A4 and Cyp3A5 may affect success of chemotherapy. In this study we attempted to examine the effects of 12 single nucleotide polymorphisms (SNPs) of the ABCB1 gene and one SNP in each of CYP3A4 and CYP3A5 genes on the incidence of ovarian cancer in Polish women and their response to treatment.

Materials and methods: Our study included 276 patients and 369 healthy control women.

Results: The results showed no significant differences between patients and controls in allele frequencies of the tested SNPs, with one exception: rs2157926T allele decreased cancer risk by 99.4% (odds ratio, 0.006). Moreover, rs2032582T increased fourfold the risk of metastasis. Finally, rs1128503CC genotype prolonged survival (p=0.024778).

Conclusion: These findings may contribute to a better prediction of therapy outcome.

Keywords: ABCB1; CYP3A4; CYP3A5; Ovarian cancer; genetics.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Cytochrome P-450 CYP3A / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Incidence
  • Middle Aged
  • Multivariate Analysis
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / genetics*
  • Poland / epidemiology
  • Polymorphism, Single Nucleotide*
  • Survival Analysis
  • Treatment Outcome

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A