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

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.

miR-146a and miR-196a2 polymorphisms in ovarian cancer risk

“…Many environmental and lifestyle factors are involved in the development of ovarian cancer, including early menarche, late menopause, the choice not to or inability to bear children, higher body mass index, family history of cancer, and long-term use of estrogen-replacement therapy and ovulation-inducing drugs (Brekelmans, 2003;Romero and Bast, 2015). Previous studies have reported that hereditary factors also contribute to ovarian cancer development, such as BRCA2, PALB2, X-ray repair cross-complementing group 2, MTHFR, calcium-sensing receptor, and vascular endothelial growth factor genes (Janardhan et al, 2015;Nakagomi et al, 2015;Shi and Shen, 2015;Su et al, 2015;Yan et al, 2015;Zhai et al, 2015).…”

Polymorphisms in the vascular endothelial growth factor (VEGF) gene associated with asthma

“…We found that the T allele in the asthma group was present in a significantly higher proportion than in the control group. The VEGF rs3025039 SNP is not only associated with asthma (Lachheb et al, 2008); like the VEGF rs3025020 polymorphism, rs3025039 is also associated with other diseases, for example, bisphosphonate-related osteonecrosis of the jaw (Choi et al, 2015) and ovarian cancers (Janardhan et al, 2015). Compared with healthy controls, the frequency of the T allele of rs3025039 is significantly higher in patients with HCH (He et al, 2015).…”

Vascular endothelial growth factor G+405C polymorphism may contribute to the risk of developing papillary thyroid carcinoma

“…Vascular endothelial growth factor polymorphisms have been implicated in the susceptibility to several cancers including breast, cervical, ovarian, colorectal and lung cancers. There are only two studies in literature investigating the −2578, +405, +936, and −141 locuses of VEGF gene .…”