Abstract
BACKGROUND: Ovarian cancer is the fifth most common cancer among women and it causes more deaths than any other type of female reproductive cancer. In the United States, approximately 22,430 new cases of ovarian cancer are diagnosed annually. Ovarian cancer is a cancerous growth arising from the ovary. Infertile women and those with a condition called endometriosis, those who have never been pregnant and those who use postmenopausal estrogen replacement therapy are at increased risk. Among the causes of cancers, epigenetic change like hypermethylation of tumor suppressor genes has been one of the main routes for the development of cancer. The aim of this study was to identify promoter hypermethylation in CpG islands of RASSF1A gene in ovarian cancer patients among the Kashmiri population.
METHODS: This was a hospital-based case-control study. We analyzed the methylation status of CpG islands in the RASSF1A gene in histopathologically confirmed ovarian cancer samples and histopathologically normal ovarian tissues using methylation specific polymerase chain reaction (MS-PCR). Chi square test with odds ratio was used to ascertain whether theresults were statistically significant and a p-value < 0.01 was considered statistically significant.
RESULTS: Subjects with histopathologically confirmed ovarian carcinoma (50 cases) and histopathologically confirmed normal ovaries (20 controls) were evaluated. The epigenetic analysis of the cases and controls revealed that the Kashmiri population has a different hypermethylation profile of RASSF1A gene promoter. We found that 66% of the cases had RASSF1A promoter hypermethylation as compared to normal controls in which only 10% were hypermethylated. The association of promoter hypermethylation with ovarian cancer was statistically significant (OR= 17.47, 95% CI=3.62-84.32, p=0.0001).
CONCLUSION: The RASSF1A gene promoter is often methylated in ovarian cancer patients of Kashmiri origin. The hypermethylation of RASSF1A may be one of the mechanisms that derive uninterrupted cell division and growth, a hallmark of malignant cells. Whether growth rate of cancer cells is decreased by modulating RASSF1A gene expression with demethylating agents and DNA methylation inhibitors needs further study.