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.
Highlights
Ovarian cancer, the leading cause of death from gynaecological malignancies is the fifth most common cause of mortality in women of the Caucasian race
The six polymorphisms genotyped in 300 cases and 320 controls were all found to be in Hardy-Wienberg equilibrium
A total of eleven clinicopathological factors were included into the study like the age at diagnosis, menstrual status, Federation of Gynecology and Obstetrics (FIGO) stage, grade, histopathology, bilateral affliction of the ovaries, preoperative plasma CA-125 levels, tumour type, presence or absence of ascites, presence or absence of residual disease and recurrence within a period of one year post operative surgery. (S2 Table enlists the clinicopathological factors included into the study)
Summary
The leading cause of death from gynaecological malignancies is the fifth most common cause of mortality in women of the Caucasian race. Survival is directly related to stage with a 5 year survival of 93% for those diagnosed with localized disease, but only 31% for those with distant disease. Two-thirds of patients present with distant disease at the time of diagnosis. In India, there has been a low incidence but a steady increase in the age-standardized prevalence rate of ovarian cancer by 3% per year in different state registries over a period of time [1]. Majority of ovarian cancers (80–90%) are epithelial ovarian tumours (EOCs). A lack of practical screening methods and the absence of clear symptoms in the early stages of tumour progression have made EOCs difficult to treat successfully. Even with contemporary chemotherapy, most patients with advanced disease relapse and die of the disease
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