Investigating impact of Vascular Endothelial Growth Factor Polymorphisms in Epithelial Ovarian Cancers: A Study in the Indian Population

PLoS One. 2015 Jul 9;10(7):e0131190. doi: 10.1371/journal.pone.0131190. eCollection 2015.

Abstract

Epithelial ovarian cancer is one of the increasingly incident malignancies that is notorious because of its evasiveness for early diagnosis and high mortality rates. Epithelial ovarian cancers are highly dependent on pathologic vasculature and Vascular Endothelial Growth Factor is known to be one of the most efficient angiogenic factors. Polymorphisms of the VEGF gene, in this study, were assessed for association with the malignancy and other clinico-pathological factors. 300 case samples and 320 age and mensus status matched controls were inculcated into the study. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were the six single nucleotide polymorphisms that were scrutinized. Genotyping was carried out by polymerase chain reaction and restriction fragment length polymorphism. rs 3025039 showed immense promise as a marker for disease aggression and recurrence and a factor for poor prognosis. rs699947 showed least association with the disease and clinico-pathologic factors studied. rs833061, rs 1570360 showed significant association with some clinico-pathological factors such as bilateral affliction of ovaries and post operative CA-125 levels. rs2010963 associated with presence of ascites in higher volumes. The SNPs under consideration showed no formidable linkage in our study samples. A haplotype analysis (excluding rs699947 and rs1413711) revealed 5 frontrunners being present in >85% of the population with TGGC and CGCC associating significantly as protective and risk factors respectively. These haplotypes showed a dose dependent additive effect of their seeming functionality. This study is unique and a first of its kind carried out in the Indian population of South-east Asia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CA-125 Antigen / metabolism
  • Carcinoma, Ovarian Epithelial
  • Chi-Square Distribution
  • Disease Progression
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Humans
  • India
  • Linkage Disequilibrium
  • Logistic Models
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology
  • Neoplasms, Glandular and Epithelial / surgery
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / surgery
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • CA-125 Antigen
  • Vascular Endothelial Growth Factor A

Grants and funding

This work was supported by the Indian Council of Medical Research, Ref No: 5/13/28/2010-NCD-III. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.